bluuebunny/crossref_metadata_2025 huggingface dataset:
Staff concerns in heroin‐assisted treatment centres
Authors: DEMARET I. , LEMAÎTRE A. , ANSSEAU M.
Published: September 2011

Accessible summary

For some heron addicts, heroin‐assisted treatment is more efficacious than methadone treatment.

Seven European countries have implemented outpatient centres where patients self‐administer pharmaceutical heroin under close supervision.

Nurses deliver pharmaceutical heroin and supervise administration. The two main concerns are overdosing and smuggling.

Nurses are convinced of the utility of this treatment for severe heroin addicts.

Heroin‐assisted treatment (HAT) is a solution for improving the condition of treatment‐resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre.
Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug‐specific T cells
Authors: Daubner B. , Groux‐Keller M. , Hausmann O. V. , Kawabata T. , Naisbitt D. J. , Park B. K. , Wendland T. , Lerch M. , Pichler W. J.
Published: September 2011

To cite this article: Daubner B, Groux‐Keller M, Hausmann OV, Kawabata T, Naisbitt DJ, Park BK, Wendland T, Lerch M, Pichler WJ. Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug‐specific T cells. Allergy 2012; 67: 58–66.

Background:  Up to 10% of patients with severe immune‐mediated drug hypersensitivity reactions have tendencies to develop multiple drug hypersensitivities (MDH). The reason why certain individuals develop MDH and the underlying pathomechanism are unclear. We investigated different T cell subpopulations in MDH patients and compared them with patients allergic to a single drug and with healthy controls (HC).

Methods:  We analyzed the in vitro reactivity of peripheral blood mononuclear cells from MDH patients (n = 7), patients with hypersensitivity to a single drug (monoallergic, n = 6), and healthy controls (HD) (n = 6) to various drugs (mainly antibiotics and antiepileptics). By depleting and selectively re‐adding CD4+ CD25bright T cells (T regulatory cells, Treg), their effect on drug‐specific T cell reactivity was analyzed. The phenotype of reacting T cells was determined ex vivo by staining for markers of activation (CD38) and cell exhaustion (PD‐1).

Results:  No functional deficiency of Treg cells was observed in all drug‐allergic patients. Drug‐reactive T cells from MDH patients were found in the CD4+ CD25dim T cell fraction and showed enhanced CD38 and PD‐1 expression, while those from monoallergic patients reside in the resting CD4+ CD25neg T cell fraction.

Conclusion:  In patients with MDH, the drug‐reactive T cells are contained in an in vivo pre‐activated T cell fraction. Therefore, they may show a lower threshold for activation by drugs. The reason for this in vivo T cell pre‐activation needs further investigations.
Could shading reduce the negative impacts of drought on coffee? A morphophysiological analysis
Authors: Cavatte Paulo C. , Oliveira Álvaro A. G. , Morais Leandro E. , Martins Samuel C. V. , Sanglard Lílian M. V. P. , DaMatta Fábio M.
Published: September 2011

Based on indirect evidence, it was previously suggested that shading could attenuate the negative impacts of drought on coffee (Coffea arabica), a tropical crop species native to shady environments. A variety (47) of morphological and physiological traits were examined in plants grown in 30‐l pots in either full sunlight or 85% shade for 8 months, after which a 4‐month water shortage was implemented. Overall, the traits showed weak or negligible responses to the light × water interaction, explaining less than 10% of the total data variation. Only slight variations in biomass allocation were observed in the combined shade and drought treatment. Differences in relative growth rates were mainly associated with physiological and not with morphological adjustments. In high light, drought constrained the photosynthetic rate through stomatal limitations with no sign of apparent photoinhibition; in low light, such constraints were apparently linked to biochemical factors. Sun‐grown plants displayed osmotic adjustments, decreased tissue elasticities and improved long‐term water use efficiencies, especially under drought. Regardless of the water availability, higher concentrations of lipids, total phenols, total soluble sugars and lignin were found in high light compared to shade conditions, in contrast to the effects on cellulose and hemicellulose concentrations. Proline concentrations increased in water‐deprived plants, particularly those grown under full sun. Phenotypic plasticity was much higher in response to the light than to the water supply. Overall, shading did not alleviate the negative impacts of drought on the coffee tree.
Importance of carbohydrate sources to the reproductive output of the wheat armywormPseudaletia sequax
Authors: Marchioro Cesar A. , Foerster Luís A.
Published: September 2011

The importance of nutrients consumed by adults differs among lepidopteran species. Knowledge of adult nutritional requirements is particularly useful when adopting biological control strategies that involve the use of flowering plants to improve the effectiveness of natural enemies. This is because nectar may also serve as a carbohydrate source for the pest.

We evaluated the effect of different sources and concentrations of carbohydrate consumed by adults on the performance and fitness of the wheat armywormPseudaletia sequaxFranclemont, which is an important pest of cereal crops.

The consumption of carbohydrates by the adults significantly increased the length of the oviposition period, fecundity, fertility and longevity ofP. sequax. Adult nutrition also affected the daily oviposition pattern of the females.

The demographic parameters estimated for each diet regime (i.e. intrinsic rate of increase, finite rate of increase and net reproductive rate) were influenced by adult nutrition. These parameters also varied according to the source and concentration of carbohydrates.

The results obtained in the present study suggest that the use of perennial flowering plants to provide a food source for natural enemies can also favour the pest.
‘My Brilliant Career’? New Organizational Forms and Changing Managerial Careers in Japan, the UK, and USA
Authors: Hassard John , Morris Jonathan , McCann Leo
Published: September 2011

abstract

The end of the traditional management career has been heralded with supporting, albeit largely anecdotal, data. The ‘old’ career was set within internal labour markets in large organizations and characterized by long‐term stability. The ‘new’ arrangements have apparently shifted responsibility from employer to employee, with careers being developed across organizations. Such change is premised on new organizational forms and is often associated with a growing sense of employee insecurity. We explore the reality of this ‘new’ scenario through interpretation of in‐depth semi‐structured interviews conducted with middle and senior human resources managers in large firms in Japan, the UK, and USA. The data indicate that most of our case study organizations had downsized and delayered, with hybrid structural forms emerging. Career prospects were diminished, with fewer vertical promotions and a greater emphasis on lateral ‘development’; middle managers were generally resentful of such factors and forces. Although not directly reflective of ‘Anglo‐American’ business practice, similar changes to career trajectories were witnessed in Japan as in the UK and USA.
The Deliberative Poll as a Method for Generating Informed Opinion on Immigration
Authors: Fiber‐Ostrow Pamela , Hill Sarah A.
Published: September 2011

The articles in this collection broadly address the social psychology of immigration and explore ways to improve relationships between natives and nonnatives in the United States. In this comment, we propose the Deliberative Poll as an additional tool for the study of opinion on immigration and for improving relationships among the groups.
Adolescent Work Experiences and Family Formation Behavior
Authors: Staff Jeremy , VanEseltine Matthew , Woolnough April , Silver Eric , Burrington Lori
Published: September 2011

A long‐standing critique of adolescent employment is that it engenders a precocious maturity of more adult‐like roles and behaviors, including school disengagement, substance use, sexual activity, inadequate sleep and exercise, and work‐related stress. Though negative effects of high‐intensity work on adolescent adjustment have been found, little research has addressed whether such work experiences are associated with precocious family formation behaviors in adolescence, such as sexual intercourse, pregnancy, residential independence, and union formation. Using data from the National Longitudinal Study of Adolescent Health, we find that teenagers who spend long hours on the job during the school year are more likely to experience these family formation behaviors earlier than youth who work moderately or not at all.
Testing Competing Capital Structure Theories of Nonprofit Organizations
Authors: Calabrese Thad D.
Published: September 2011

The static trade‐off and pecking order capital structure theories are analyzed and applied to nonprofit organizations. In addition, this paper also considers how nonprofits adjust their leverage over time. The analyses consider the unique role of donor‐restricted endowments in the decision to borrow, as well as different types of borrowing by nonprofits. The results indicate that nonprofit capital structure choices are best explained using the pecking order theory, in which internal funds are preferred over external borrowing. Further, nonprofit endowment is not found to increase leverage. Despite the unambiguous findings across varying definitions of leverage, the results also suggest that a “modified pecking order” is a more apt descriptor of nonprofit behavior.
Mexican Municipalities and the Flypaper Effect
Authors: CáRDENAS OSCAR J. , SHARMA AMARENDRA
Published: September 2011

We investigate the phenomenon of flypaper effect and its relationship with the local tax effort by using a panel data comprising approximately 48 percent of the Mexican municipalities. Our estimations based on the fixed effect and difference GMM estimators confirm the existence of flypaper effect. Moreover, we find evidence to suggest that the richer municipalities are likely to experience substitution effect, i.e., the lower levels of tax effort. We also find that the magnitude of the flypaper effect is a decreasing function of the economic wellbeing of municipalities. This calls for an overhaul of the allocation mechanism of unconditional grants to the Mexican municipalities.
In Search of Attention
Authors: DA ZHI , ENGELBERG JOSEPH , GAO PENGJIE
Published: September 2011

We propose a new and direct measure of investor attention using search frequency in Google (Search Volume Index (SVI)). In a sample of Russell 3000 stocks from 2004 to 2008, we find that SVI (1) is correlated with but different from existing proxies of investor attention; (2) captures investor attention in a more timely fashion and (3) likely measures the attention of retail investors. An increase in SVI predicts higher stock prices in the next 2 weeks and an eventual price reversal within the year. It also contributes to the large first‐day return and long‐run underperformance of IPO stocks.
Free Cash Flow, Issuance Costs, and Stock Prices
Authors: DÉCAMPS JEAN‐PAUL , MARIOTTI THOMAS , ROCHET JEAN‐CHARLES , VILLENEUVE STÉPHANE
Published: September 2011

We develop a dynamic model of a firm facing agency costs of free cash flow and external financing costs, and derive an explicit solution for the firm's optimal balance sheet dynamics. Financial frictions affect issuance and dividend policies, the value of cash holdings, and the dynamics of stock prices. The model predicts that the marginal value of cash varies negatively with the stock price, and positively with the volatility of the stock price. This yields novel insights on the asymmetric volatility phenomenon, on risk management policies, and on how business cycles and agency costs affect the volatility of stock returns.
A Unified Theory of Tobin's q, Corporate Investment, Financing, and Risk Management
Authors: BOLTON PATRICK , CHEN HUI , WANG NENG
Published: September 2011

We propose a model of dynamic investment, financing, and risk management for financially constrained firms. The model highlights the central importance of the endogenous marginal value of liquidity (cash and credit line) for corporate decisions. Our three main results are: (1) investment depends on the ratio of marginal q to the marginal value of liquidity, and the relation between investment and marginal q changes with the marginal source of funding; (2) optimal external financing and payout are characterized by an endogenous double‐barrier policy for the firm's cash‐capital ratio; and (3) liquidity management and derivatives hedging are complementary risk management tools.
The Real and Financial Implications of Corporate Hedging
Authors: CAMPELLO MURILLO , LIN CHEN , MA YUE , ZOU HONG
Published: September 2011

We study the implications of hedging for corporate financing and investment. We do so using an extensive, hand‐collected data set on corporate hedging activities. Hedging can lower the odds of negative realizations, thereby reducing the expected costs of financial distress. In theory, this should ease a firm's access to credit. Using a tax‐based instrumental variable approach, we show that hedgers pay lower interest spreads and are less likely to have capital expenditure restrictions in their loan agreements. These favorable financing terms, in turn, allow hedgers to invest more. Our tests characterize two exact channels—cost of borrowing and investment restrictions—through which hedging affects corporate outcomes. The analysis shows that hedging has a first‐order effect on firm financing and investment, and provides new insights into how hedging affects corporate value. More broadly, our study contributes novel evidence on the real consequences of financial contracting.
Production and Certification of a Unique Set of Isotope and Delta Reference Materials for Boron Isotope Determination in Geochemical, Environmental and Industrial Materials
Authors: Vogl Jochen , Rosner Martin
Published: September 2011

Isotopic reference materials are essential to enable reliable and comparable isotope data. In the case of boron only a very limited number of such materials is available, thus preventing adequate quality control of measurement results and validation of analytical procedures. To address this situation a unique set of two boron isotope reference materials (ERM‐AE102a and ‐AE104a) and three offset δ11B reference materials (ERM‐AE120, ‐AE121 and ‐AE122) were produced and certified. The present article describes the production and certification procedure in detail. The isotopic composition of all the materials was adjusted by mixing boron parent solutions enriched in 10B or 11B with a boron parent solution having a natural isotopic composition under full gravimetric control. All parent solutions were analysed for their boron concentration as well as their boron isotopic composition by thermal ionisation mass spectrometry (TIMS) using isotope dilution as the calibration technique. For all five reference materials the isotopic composition obtained on the basis of the gravimetric data agreed very well with the isotopic composition obtained from different TIMS techniques. Stability and homogeneity studies that were performed showed no significant influence on the isotopic composition or on the related uncertainties. The three reference materials ERM‐AE120, ERM‐AE121 and ERM‐AE122 are the first reference materials with natural δ11B values not equal to 0‰. The certified δ11B values are −20.2‰ for ERM‐AE120, 19.9‰ for ERM‐AE121 and 39.7‰ for ERM‐AE122, each with an expanded uncertainty (k = 2) of 0.6‰. These materials were produced to cover about three‐quarters of the known natural boron isotope variation. The 10B enriched isotope reference materials ERM‐AE102a and ERM‐AE104a were produced for industrial applications utilising 10B for neutron shielding purposes. The certified 10B isotope abundances are 0.29995 for ERM‐AE102a and 0.31488 for ERM‐AE104a with expanded uncertainties (k = 2) of 0.00027 and 0.00028, respectively. Together with the formerly certified ERM‐AE101 and ERM‐AE103 a unique set of four isotope reference materials and three offset δ11B reference materials for boron isotope determination are now available from European Reference Materials.
The effect of non‐steroidal anti‐inflammatory drugs on the endothelial function of patients with osteoarthritis in short term
Authors: SOLMAZ Dilek , SARI Ismail , CAN Gercek , AKAR Servet , CEYLAN Isin , SECIL Mustafa , AKKOC Nurullah
Published: September 2011

Objective:  Our primary aim was to test whether non‐steroid anti‐inflammatory drug (NSAID) use may account for endothelial dysfunction (ED) in the acute period. Additionally, we also aimed to compare the effect of diclofenac and naproxen on endothelial function.

Methods:  Forty patients with osteoarthritis (OA) were included in the study. Subjects currently receiving NSAIDs were asked to discontinue their anti‐inflammatory medications (for at least 5 days) before the study. After the wash‐out period, all subjects underwent vascular ultrasound measurements. Following baseline vascular imaging, patients were randomly assigned in a 1 : 1 ratio to receive either diclofenac (75 mg twice daily, n = 20), or naproxen (500 mg twice daily, n = 20) for 7 days. Endothelial function was evaluated by using the flow‐mediated dilatation (FMD) method, at baseline, and after 1 week of NSAID treatment.

Results:  There were 40 OA patients (4 male, 36 female). The median age of the patients was 60 ± 14 years. There were equal numbers of subjects in each treatment group. Age, sex distribution, body mass index, serum lipids, erythrocyte sedimentation rate, C‐reactive protein and fasting glucose levels were similar between the diclofenac and naproxen groups (P > 0.05). The brachial artery diameter (BAD), endothelium‐dependent vasodilatation (FMD%) and nitroglycerin‐induced endothelium‐independent vasodilatation (NTG%) values were not different between pretreatment and on the seventh day in the NSAID treatment groups (P > 0.05). Subgroup analysis also showed similar values of BAD, FMD%, and NTG% between naproxen and diclofenac groups (P > 0.05).

Conclusion:  Our results suggest that nonselective cyclo‐oxygenase antagonists naproxen and diclofenac have no effect on endothelial function during short‐term use.
Model Remodeling-Osteocytes Take Center Stage
Authors: Cheng Mickie
Published: September 2011

Unexpectedly, bone matrix–embedded osteocytes, not osteoblasts, maintain the uncertain balance between bone formation and resorption that goes awry in osteoporosis.
Surface Layers of Clostridium difficile Endospores
Authors: Permpoonpattana Patima , Tolls Elisabeth H. , Nadem Ramez , Tan Sisareuth , Brisson Alain , Cutting Simon M.
Published: September 2011

Clostridium difficile
is an important human pathogen and one where the primary cause of disease is due to the transmission of spores. We have investigated the proteins found in the outer coat layers of
C. difficile
spores of pathogenic strain 630 (CD630). Five coat proteins, CotA, CotB, CotCB, CotD, and CotE, were shown to be expressed on the outer coat layers of the spore. We demonstrate that purified spores carry catalase, peroxiredoxin, and chitinase activity and that this activity correlates with the predicted functions of three spore coat proteins identified here, CotCB, CotD, and CotE. CotCB and CotD are putative manganese catalases, and CotE is a novel bifunctional protein with peroxiredoxin activity at its amino terminus and chitinase activity at its carboxy terminus. These enzymes could play an important role in coat assembly by polymerizing protein monomers in the coat. CotE, in addition to a role in macromolecular degradation, could play an important role in inflammation, and this may be of direct relevance to the development of the gastrointestinal symptoms that accompany
C. difficile
infection. Although specific enzyme activity has not yet been assigned to the proteins identified here, this work provides the first detailed study of the
C. difficile
spore coat.
Just-in-Time Control of Spo0A Synthesis in Bacillus subtilis by Multiple Regulatory Mechanisms
Authors: Chastanet Arnaud , Losick Richard
Published: September 2011

The response regulator Spo0A governs multiple developmental processes in
Bacillus subtilis
, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of
spo0A
is governed by a promoter switching mechanism, involving a vegetative, σ
A
-recognized promoter, P
v
, and a sporulation σ
H
-recognized promoter, P
s
, that is under phosphorylated Spo0A (Spo0A∼P) control. The
spo0A
regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O
1
, O
2
, O
3
, and O
4
in reverse order of their proximity to the coding sequence. Here we report that O
1
is responsible for repressing P
v
during the transition to stationary phase, that O
2
is responsible for repressing P
s
during growth, that O
3
is responsible for activating P
s
at the start of sporulation, and that O
4
is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P
v
is impeded due to RNA secondary structure whereas mRNAs originating from P
s
are fully competent for protein synthesis. We propose that the opposing actions of O
2
and O
3
and the enhanced translatability of mRNAs originating from P
s
create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.
Competence in Streptococcus pneumoniae Is Regulated by the Rate of Ribosomal Decoding Errors
Authors: Stevens Kathleen E. , Chang Diana , Zwack Erin E. , Sebert Michael E.
Published: September 2011

Competence for genetic transformation in
Streptococcus pneumoniae
develops in response to accumulation of a secreted peptide pheromone and was one of the initial examples of bacterial quorum sensing. Activation of this signaling system induces not only expression of the proteins required for transformation but also the production of cellular chaperones and proteases. We have shown here that activity of this pathway is sensitively responsive to changes in the accuracy of protein synthesis that are triggered by either mutations in ribosomal proteins or exposure to antibiotics. Increasing the error rate during ribosomal decoding promoted competence, while reducing the error rate below the baseline level repressed the development of both spontaneous and antibiotic-induced competence. This pattern of regulation was promoted by the bacterial HtrA serine protease. Analysis of strains with the
htrA
(S234A) catalytic site mutation showed that the proteolytic activity of HtrA selectively repressed competence when translational fidelity was high but not when accuracy was low. These findings redefine the pneumococcal competence pathway as a response to errors during protein synthesis. This response has the capacity to address the immediate challenge of misfolded proteins through production of chaperones and proteases and may also be able to address, through genetic exchange, upstream coding errors that cause intrinsic protein folding defects. The competence pathway may thereby represent a strategy for dealing with lesions that impair proper protein coding and for maintaining the coding integrity of the genome.

IMPORTANCE
The signaling pathway that governs competence in the human respiratory tract pathogen
Streptococcus pneumoniae
regulates both genetic transformation and the production of cellular chaperones and proteases. The current study shows that this pathway is sensitively controlled in response to changes in the accuracy of protein synthesis. Increasing the error rate during ribosomal decoding induced competence, while decreasing the error rate repressed competence. This pattern of regulation was promoted by the HtrA protease, which selectively repressed competence when translational fidelity was high but not when accuracy was low. Our findings demonstrate that this organism is able to monitor the accuracy of information used for protein biosynthesis and suggest that errors trigger a response addressing both the immediate challenge of misfolded proteins and, through genetic exchange, upstream coding errors that may underlie protein folding defects. This pathway may represent an evolutionary strategy for maintaining the coding integrity of the genome.
A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae
Authors: Ohneck Elizabeth A. , Zalucki Yaramah M. , Johnson Paul J. T. , Dhulipala Vijaya , Golparian Daniel , Unemo Magnus , Jerse Ann E. , Shafer William M.
Published: September 2011

The MtrC-MtrD-MtrE multidrug efflux pump of
Neisseria gonorrhoeae
confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the
mtrCDE
operon is differentially regulated by both a repressor, MtrR, and an activator, MtrA. The
mtrR
gene lies 250 bp upstream of and is transcribed divergently from the
mtrCDE
operon. Previous research has shown that mutations in the
mtrR
coding region and in the
mtrR
-
mtrCDE
intergenic region increase levels of gonococcal antibiotic resistance and
in vivo
fitness. Recently, a C-to-T transition mutation 120 bp upstream of the
mtrC
start codon, termed
mtr
120
, was identified in strain MS11 and shown to be sufficient to confer high levels of antimicrobial resistance when introduced into strain FA19. Here we report that this mutation results in a consensus −10 element and that its presence generates a novel promoter for
mtrCDE
transcription. This newly generated promoter was found to be stronger than the wild-type promoter and does not appear to be subject to MtrR repression or MtrA activation. Although rare, the
mtr
120
mutation was identified in an additional clinical isolate during sequence analysis of antibiotic-resistant strains cultured from patients with gonococcal infections. We propose that
cis
-acting mutations can develop in gonococci that significantly alter the regulation of the
mtrCDE
operon and result in increased resistance to antimicrobials.

IMPORTANCE
Gonorrhea is the second most prevalent sexually transmitted bacterial infection and a worldwide public health concern. As there is currently no vaccine against
Neisseria gonorrhoeae
, appropriate diagnostics and subsequent antibiotic therapy remain the primary means of infection control. However, the effectiveness of antibiotic treatment is constantly challenged by the emergence of resistant strains, mandating a thorough understanding of resistance mechanisms to aid in the development of new antimicrobial therapies and genetic methods for antimicrobial resistance testing. This study was undertaken to characterize a novel mechanism of antibiotic resistance regulation in
N. gonorrhoeae
. Here we show that a single base pair mutation generates a second, stronger promoter for
mtrCDE
transcription that acts independently of the known efflux system regulators and results in high-level antimicrobial resistance.
Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis
Authors: Ierardi Enzo , Giorgio Floriana , Zotti Mariangela , Rosania Rosa , Principi Mariabeatrice , Marangi Stefania , Della Valle Nicola , De Francesco Vincenzo , Di Leo Alfredo , Ingrosso Marcello , Panella Carmine
Published: September 2011

Background

It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders.

Aim of the study

A ‘post-hoc’ retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing.

Material and methods

Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2–3 to 0. ANOVA plus Student–Newman–Keuls was used for statistical analysis.

Results

The authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls.

Conclusions

Balanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.
Cerebral proliferative angiopathy
Authors: Marks Michael P , Steinberg Gary K
Published: September 2011

Cerebral proliferative angiopathy is a rare lesion marked by diffuse intravascular shunting, which should be differentiated from brain arteriovenous malformations. A patient is presented with cerebral proliferative angiopathy and documented progressive development of hypervascular shunting involving extensive portions of the left hemisphere. The patient had angiographic and laboratory evidence of angiogenesis and a progressive neurologic deterioration which corresponded to the development of her lesion. This is the first case which documents the progressive proliferative changes seen with this abnormality.
CT perfusion-guided patient selection for endovascular treatment of acute ischemic stroke is safe and effective
Authors: Turk Aquilla , Magarik Jordan Asher , Chaudry Imran , Turner Raymond D , Nicholas Joyce , Holmstedt Christine A , Chalela Julio , Hays Angela , Lazaridis Christos , Jauch Edward , Chimowitz Marc , Turan Tanya , Adams Robert
Published: September 2011

Background

Traditional treatment in acute ischemic stroke is based on time criteria when administering intravenous and intra-arterial therapies. However, recent evidence suggests that image-based criteria may be useful for selecting patients for intra-arterial interventions. The use of CT perfusion (CTP)-based criteria, regardless of time from symptom onset, in patient selection for intra-arterial treatment of ischemic stroke was assessed.

Methods

Patients with ischemic stroke who presented to the emergency department at the Medical University of South Carolina with a National Institute of Health Stroke Scale score of ≥ 8, regardless of time from symptom onset, were assessed retrospectively. CTP maps were qualitatively assessed for the presence of penumbra and infarction. Selected patients underwent mechanical aspiration of their occlusion using the Penumbra system. Functional outcome was then recorded using the modified Rankin scale (mRS) at 90 days or the closest follow-up to 90 days.

Results

53 patients were included in the study. The median time from symptom onset to groin vascular access was 6.3 h. Eight patients (15%) had bleeding complications including subarachnoid hemorrhage, parenchymal hemorrhage and intraventricular hemorrhage. After CTP-based selection, the patients were divided into two groups for analysis: ≤6 h and >6 h from symptom onset to endovascular procedure. No difference was found in functional outcome between the two groups (38.5% and 40.7% achieved 90-day mRS ≤2, respectively (p=1.0) and 57.7% and 51.9% achieved 90-day mRS ≤3, respectively (p=0.785)). There was no difference in the rate of intracranial hemorrhage between the two groups (11.5 vs 18.5, p=0.704).

Conclusion

This study demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CTP selection rather than time-guided selection. These findings suggest that endovascular reperfusion in ischemic stroke may be effective and safe, and may allow patient selection not solely based on time from symptom onset.
Proteasome functional insufficiency in cardiac pathogenesis
Authors: Wang Xuejun , Li Jie , Zheng Hanqiao , Su Huabo , Powell Saul R.
Published: September 2011

The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past several years, remarkable progress in understanding the mechanisms that regulate UPS-mediated protein degradation has been achieved. A transgenic mouse model of benign enhancement of cardiac proteasome proteolytic function has been created. This has led to the first demonstration of the necessity of proteasome functional insufficiency in the genesis of important pathological processes. Cardiomyocyte-restricted enhancement of proteasome proteolytic function by overexpression of proteasome activator 28α protects against cardiac proteinopathy and myocardial ischemia-reperfusion injury. Additionally, exciting advances have recently been achieved in the search for a pharmacological agent to activate the proteasome. These breakthroughs are expected to serve as an impetus to further investigation into the involvement of UPS dysfunction in molecular pathogenesis and to the development of new therapeutic strategies for combating heart disease. An interplay between the UPS and macroautophagy is increasingly suggested in noncardiac systems but is not well understood in the cardiac system. Further investigations into the interplay are expected to provide a more comprehensive picture of cardiac protein quality control and degradation.
Heterotrimeric Gi/Goproteins modulate endothelial TLR signaling independent of the MyD88-dependent pathway
Authors: Dauphinee Shauna M. , Voelcker Verena , Tebaykina Zinaida , Wong Fred , Karsan Aly
Published: September 2011

The innate immune recognition of bacterial lipopolysaccharide (LPS) is mediated by Toll-like receptor 4 (TLR4) and results in activation of proinflammatory signaling including NF-κB and MAPK pathways. Heterotrimeric G proteins have been previously implicated in LPS signaling in macrophages and monocytes. In the present study, we show that pertussis toxin sensitive heterotrimeric G proteins (Gαi/o) are involved in the activation of MAPK and Akt downstream of TLR2, TLR3, and TLR4 in endothelial cells. Gαi/oare also required for full activation of interferon signaling downstream of TLR3 and TLR4 but are not required for the activation of NF-κB. We find that Gαi/o-mediated activation of the MAPK is independent of the canonical MyD88, interleukin-1 receptor-associated kinase, and tumor necrosis factor receptor-associated factor 6 signaling cascade in LPS-stimulated cells. Taken together, the data presented here suggest that heterotrimeric G proteins are widely involved in TLR pathways along a signaling cascade that is distinct from MyD88-TRAF6.
Silvicultural Attempts to Induce Browse Resistance in Conifer Seedlings
Authors: Kimball Bruce A. , Pfund Fred , Gourley Mark , Griffin Doreen L. , Russell John H.
Published: September 2011

A multiyear study was conducted to determine if soil amendment combined with topical application of elemental sulfur could be employed to reduce deer browse damage to four conifer species. Fertilizer and sulfur were applied to conifer seedlings at seven sites near Corvallis, OR. Growth and browse damage data were collected for all seedlings over a period of 17 months. Additionally, foliar concentrations of monoterpenes and simple carbohydrates were assessed in western redcedar (Thuja plicata) seedlings over a period of three years. Fertilization and sulfur treatments had a moderate impact on growth and no influence on browse damage or the chemical responses. Over the course of the study, browse damage diminished while foliar monoterpene concentrations increased in redcedar. It appears that silvicultural manipulation via sulfur application and/or soil amendment cannot accelerate or alter the ontogenetical changes that may naturally defend seedlings against mammalian herbivores. In a brief trial with captive deer, redcedar browse resistance was influenced by seedling maturation, but not monoterpene content. Other maturation effects may yield significant browse protection to young seedlings.
Horizontal Acoustic Barriers for Protection from Seismic Waves
Authors: Kuznetsov Sergey V. , Nafasov Aybek E.
Published: September 2011

The basic idea of a seismic barrier is to protect an area occupied by a building or a group of buildings from seismic waves. Depending on nature of seismic waves that are most probable in a specific region, different kinds of seismic barriers can be suggested. Herein, we consider a kind of a seismic barrier that represents a relatively thin surface layer that prevents surface seismic waves from propagating. The ideas for these barriers are based on one Chadwick′s result concerning nonpropagation condition for Rayleigh waves in a clamped half‐space, and Love′s theorem that describes condition of nonexistence for Love waves. The numerical simulations reveal that to be effective the length of the horizontal barriers should be comparable to the typical wavelength.
Existence and Uniqueness of Positive Solution for a Boundary Value Problem of Fractional Order
Authors: Caballero J. , Harjani J. , Sadarangani K.
Published: September 2011

We are concerned with the existence and uniqueness of positive solutions for the following nonlinear fractional boundary value problem: , 0 ≤ t ≤ 1, 3 < α ≤ 4, u(0) = u′(0) = u″(0) = u″(1) = 0, where denotes the standard Riemann‐Liouville fractional derivative. Our analysis relies on a fixed point theorem in partially ordered sets. Some examples are also given to illustrate the results.
Vulvar Pyogenic Granuloma in a Postmenopausal Woman: Case Report and Review of the Literature
Authors: Arikan Deniz Cemgil , Kiran Gurkan , Sayar Hamide , Kostu Bulent , Coskun Ayhan , Kiran Hakan
Published: September 2011

Introduction. Although pyogenic granulomas (PG) are common and benign vascular proliferations of the skin and mucous membranes, they are relatively rare on the vulva.Case Presentation. A 57-year-old G7P7 postmenopausal woman presented with a 3-year history of a foul smell and bleeding lesions in the genital region. A gynecologic examination revealed multiple large papillomatous, pedunculated, and lobulated lesions that were cherry-red and infective in appearance. There was a 2-cm lesion at the upper intersection of the labia majora, a 2-cm lesion on the right labium majus, and a 4-cm lesion on the clitoris. The patient complained of itching, and the lesions were asymptomatic, except for occasional bleeding. All lesions were excised and sent for histopathological examination, which revealed an ulcerated polypoidal structure with extensive proliferation of vascular channels lined by a single layer of endothelium. The histopathological features were consistent with PG.Conclusion. The present case is the first case of multiple pyogenic granulomas on the vulva in a postmenopausal woman.
Protection of Flax/PLLA Biocomposites from Seawater Ageing by External Layers of PLLA
Authors: Le Duigou A. , Deux J. M. , Davies P. , Baley C.
Published: September 2011

Biocomposites are sensitive to water, and previous work on flax reinforced PLLA showed a large drop in mechanical properties after immersion (Le Duigou et al. 2009). Unreinforced PLLA was much less sensitive. This paper presents a strategy to reduce the influence of wet ageing by adding extra layers of PLLA on the biocomposite surface. Weight gain measurements show that a PLLA coating 350 m thick reduces weight gain by half, and biocomposite stiffness and strength after ageing are improved by 100% compared to uncoated composite behaviour. Thermal analysis and microscopic examination are used to show damage mechanisms with and without protection. Property changes are shown to be quasilinearly related to weight gain.
XMRV Discovery and Prostate Cancer-Related Research
Authors: Kang David E. , Lee Michael C. , Das Gupta Jaydip , Klein Eric A. , Silverman Robert H.
Published: September 2011

Xenotropic murine leukemia virus-related virus (XMRV) was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), and immunosuppressed with respiratory tract infections) or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.
On the Characterization of a Class of Difference Equations
Authors: Altun Muhammed
Published: September 2011

We focus on the behavior of solutions of the difference equation xn = b1xn−1 + b2xn−2 + ⋯+bnx0 + yn, n = 1, 2, …, where (bk) is a fixed sequence of complex numbers, and (yk) is a fixed sequence in a complex Banach
space. We give the general solution of this difference equation. To examine the asymptotic behavior
of solutions, we compute the spectra of operators which correspond to such type of difference equations. These operators are represented by upper triangular or lower triangular infinite banded Toeplitz
matrices.
CML Developing Three Years after Therapy Completion in a Child with Ph(−) Pre-B-ALL
Authors: Hosseini S. , Bahoush G. H. , Vousogh P. , Ansari Sh. , Arjmandi Kh. , Sabzechian M.
Published: September 2011

We report a girl with a history of Ph(−) pre-B-ALL and three years of disease-free survival admitting to our hospital for regular end of treatment checkup with an increased white blood cell count which in follow-up studies and molecular detection of BCR-ABL (p210) fusions gene had been diagnosed as a Ph(+) typical CML. The upcoming question in this case scenario is whether developed CML is a secondary leukemia due to previous ALL chemotherapy or just a relapse case of primary leukemia.
A Rare Case of Secondary Bacterial Peritonitis fromClostridium perfringensin an Adult Patient with Noncirrhotic Ascites and a Krukenberg Tumor: Report of a Case
Authors: Kelley Scott R. , Kerlakian George M.
Published: September 2011

Secondary bacterial peritonitis, in comparison to spontaneous, presents with a surgically treatable intraabdominal source for infection such as a gastrointestinal perforation or abscess and is nearly always polymicrobial. We present a rare case of secondary bacterial peritonitis fromClostridium perfringensin an adult patient with noncirrhotic ascites and a Krukenberg tumor.
Kenaf Bast Fibers—Part II: Inorganic Nanoparticle Impregnation for Polymer Composites
Authors: Shi Jinshu , Shi Sheldon Q. , Barnes H. Michael , Horstemeyer Mark F. , Wang Ge
Published: September 2011

The objective of this study was to investigate an inorganic nanoparticle impregnation (INI) technique to improve the compatibility between kenaf bast fibers and polyolefin matrices. The Scanning Electron Microscopy (SEM) was used to examine the surface morphology of the INI-treated fibers showing that the CaCO3nanoparticle crystals grew onto the fiber surface. Energy-dispersive X-ray spectroscopy (EDS) was used to verify the CaCO3nanoparticle deposits on the fiber surface. The tension tests of the individual fiber were conducted, and the results showed that the tensile strength of the fibers increased significantly (more than 20%) after the INI treatments. Polymer composites were fabricated using the INI-treated fiber as reinforcement and polypropylene (PP) as the matrix. The results showed that the INI treatments improved the compatibility between kenaf fibers and PP matrix. The tensile modulus and tensile strength of the composites reinforced with INI-treated fibers increased by 25.9% and 10.4%, respectively, compared to those reinforced with untreated kenaf fibers.
Heavy Metal Poisoning and Cardiovascular Disease
Authors: Alissa Eman M. , Ferns Gordon A.
Published: September 2011

Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed.