bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment
Authors: Ledesma-Soto Yadira , Blanco-Favela Francisco , Fuentes-Pananá Ezequiel M , Tesoro-Cruz Emiliano , Hernández-González Rafael , Arriaga-Pizano Lourdes , Legorreta-Haquet María V , Montoya-Diaz Eduardo , Chávez-Sánchez Luis , Castro-Mussot María E , Chávez-Rueda Adriana K
Published: March 2012

Background

Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus.

Results

Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor.

Conclusions

We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.
Transgenic expression of lactoferrin imparts enhanced resistance to head blight of wheat caused by Fusarium graminearum
Authors: Han Jigang , Lakshman Dilip K , Galvez Leny C , Mitra Sharmila , Baenziger Peter Stephen , Mitra Amitava
Published: March 2012

Background

The development of plant gene transfer systems has allowed for the introgression of alien genes into plant genomes for novel disease control strategies, thus providing a mechanism for broadening the genetic resources available to plant breeders. Using the tools of plant genetic engineering, a broad-spectrum antimicrobial gene was tested for resistance against head blight caused by Fusarium graminearum Schwabe, a devastating disease of wheat (Triticum
aestivum L.) and barley (Hordeum vulgare L.) that reduces both grain yield and quality.

Results

A construct containing a bovine lactoferrin cDNA was used to transform wheat using an Agrobacterium-mediated DNA transfer system to express this antimicrobial protein in transgenic wheat. Transformants were analyzed by Northern and Western blots to determine lactoferrin gene expression levels and were inoculated with the head blight disease fungus F. graminearum. Transgenic wheat showed a significant reduction of disease incidence caused by F. graminearum compared to control wheat plants. The level of resistance in the highly susceptible wheat cultivar Bobwhite was significantly higher in transgenic plants compared to control Bobwhite and two untransformed commercial wheat cultivars, susceptible Wheaton and tolerant ND 2710. Quantification of the expressed lactoferrin protein by ELISA in transgenic wheat indicated a positive correlation between the lactoferrin gene expression levels and the levels of disease resistance.

Conclusions

Introgression of the lactoferrin gene into elite commercial wheat, barley and other susceptible cereals may enhance resistance to F. graminearum.
Laxative effects of partially defatted flaxseed meal on normal and experimental constipated mice
Authors: Xu Jiqu , Zhou Xiaoqi , Chen Chang , Deng Qianchun , Huang Qingde , Yang Jin'e , Yang Nianhong , Huang Fenghong
Published: March 2012

Background

Constipation is a very common health problem in the world. Intake of sufficient amount of dietary fibers is a cornerstone in the prevention and treatment of constipation. As a traditional medicine, flaxseed has been used to treat constipation for centuries, but the controlled trials are rare. The purpose of the present study was to assess that whether partially defatted flaxseed meal (PDFM) has the potential role to facilitate fecal output in normal and experimental constipated mice.

Methods

After supplemented with 2.5%, 5% and 10% (w/w) PDFM (L-, M- and H -PDFM) for 14 days, the constipation models of mice were induced by atropine-diphenoxylate. The small intestinal transit rates, start time of defecation, amount of defecation and wet weight of feces were researched in normal and constipation model mice.

Results

M- and H-PDFM significantly increase small intestinal transit rates in constipation model mice. All dose of PDFM markedly shortened the start time of defecation and M- and H-PDFM significantly increase stool frequency and weight in both normal and constipation model mice.

Conclusions

PDFM may be a useful laxative to facilitate fecal output in normal and constipation conditions.
A survey tool for measuring evidence-based decision making capacity in public health agencies
Authors: Jacobs Julie A , Clayton Paula F , Dove Cassandra , Funchess Tanya , Jones Ellen , Perveen Ghazala , Skidmore Brandon , Sutton Victor , Worthington Sarah , Baker Elizabeth A , Deshpande Anjali D , Brownson Ross C
Published: March 2012

Background

While increasing attention is placed on using evidence-based decision making (EBDM) to improve public health, there is little research assessing the current EBDM capacity of the public health workforce. Public health agencies serve a wide range of populations with varying levels of resources. Our survey tool allows an individual agency to collect data that reflects its unique workforce.

Methods

Health department leaders and academic researchers collaboratively developed and conducted cross-sectional surveys in Kansas and Mississippi (USA) to assess EBDM capacity. Surveys were delivered to state- and local-level practitioners and community partners working in chronic disease control and prevention. The core component of the surveys was adopted from a previously tested instrument and measured gaps (importance versus availability) in competencies for EBDM in chronic disease. Other survey questions addressed expectations and incentives for using EBDM, self-efficacy in three EBDM skills, and estimates of EBDM within the agency.

Results

In both states, participants identified communication with policymakers, use of economic evaluation, and translation of research to practice as top competency gaps. Self-efficacy in developing evidence-based chronic disease control programs was lower than in finding or using data. Public health practitioners estimated that approximately two-thirds of programs in their agency were evidence-based. Mississippi participants indicated that health department leaders' expectations for the use of EBDM was approximately twice that of co-workers' expectations and that the use of EBDM could be increased with training and leadership prioritization.

Conclusions

The assessment of EBDM capacity in Kansas and Mississippi built upon previous nationwide findings to identify top gaps in core competencies for EBDM in chronic disease and to estimate a percentage of programs in U.S. health departments that are evidence-based. The survey can serve as a valuable tool for other health departments and non-governmental organizations to assess EBDM capacity within their own workforce and to assist in the identification of approaches that will enhance the uptake of EBDM processes in public health programming and policymaking. Localized survey findings can provide direction for focusing workforce training programs and can indicate the types of incentives and policies that could affect the culture of EBDM in the workplace.
MutS homologue hMSH5: role in cisplatin-induced DNA damage response
Authors: Tompkins Joshua D , Wu Xiling , Her Chengtao
Published: March 2012

Background

Cisplatin (cis-diamminedichloroplatinum (II), CDDP) and its analogues constitute an important class of anticancer drugs in the treatment of various malignancies; however, its effectiveness is frequently affected by mutations in genes involved in the repair and signaling of cisplatin-induced DNA damage. These observations necessitate a need for a better understanding of the molecular events governing cellular sensitivity to cisplatin.

Results

Here, we show that hMSH5 mediates sensitization to cisplatin-induced DNA damage in human cells. Our study indicates that hMSH5 undergoes cisplatin-elicited protein induction and tyrosine phosphorylation. Silencing of hMSH5 by RNAi or expression of hMSH5 phosphorylation-resistant mutant hMSH5Y742F elevates cisplatin-induced G2 arrest and renders cells susceptible to cisplatin toxicity at clinically relevant doses. In addition, our data show that cisplatin promotes hMSH5 chromatin association and hMSH5 deficiency increases cisplatin-triggered γ-H2AX foci. Consistent with a possible role for hMSH5 in recombinational repair of cisplatin-triggered double-strand breaks (DSBs), the formation of cisplatin-induced hMSH5 nuclear foci is hRad51-dependent.

Conclusion

Collectively, our current study has suggested a role for hMSH5 in the processing of cisplatin-induced DSBs, and silencing of hMSH5 may provide a new means to improve the therapeutic efficacy of cisplatin.
Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α
Authors: Scuderi Caterina , Valenza Marta , Stecca Claudia , Esposito Giuseppe , Carratù Maria Rosaria , Steardo Luca
Published: March 2012

Background

In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα).

Findings

In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ1-42 and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons.

Conclusions

In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.
Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand
Authors: Avihingsanon Anchalee , Matthews Gail V , Lewin Sharon R , Marks Pip , Sasadeusz Jose , Cooper David A , Bowden Scott , Locarnini Stephen , Dore Greg J , Ruxrungtham Kiat
Published: March 2012

Background

Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited.

Methods

The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand.

Results

Early HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053).

Conclusion

EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process.

Clinical Trial number

NCT00192595.
Ex-vivo porcine organs with a circulation pump are effective for teaching hemostatic skills
Authors: Izawa Yoshimitsu , Hishikawa Shuji , Muronoi Tomohiro , Yamashita Keisuke , Suzukawa Masayuki , Lefor Alan T
Published: March 2012

Surgical residents have insufficient opportunites to learn basic hemostatic skills from clinical experience alone. We designed an ex-vivo training system using porcine organs and a circulation pump to teach hemostatic skills. Residents were surveyed before and after the training and showed significant improvement in their self-confidence (1.83 ± 1.05 vs 3.33 ± 0.87, P < 0.01) on a 5 point Likert scale. This training may be effective to educate residents in basic hemostatic skills.
The successful introduction of an adapted form of the mini extra corporeal circulation used for cardiac surgery in an obese patient
Authors: Sartini Patrizio , Winfield Anna , Bizzarri Federico
Published: March 2012

Obese patients undergoing cardiac surgery have been shown to have a high risk of developing postoperative complications, specifically: increased length of hospital stay, readmission to intensive care unit, acute renal failure, deep sternal wound infections and new onset of atrial fibrillation.

A custom-made circuit was created to allow the use of Mini Extra Corporeal Circulation (MECC) but permitting the switch to a closed siphon drainage system in the case of difficulties.

To limit artificial surface contact a small oxygenating device (Admiral, Eurosets) was employed in spite of the patients size. This adapted circuit permits a feasible and safer approach to using MECC. This report suggests that smaller oxygenators could be integrated into clinical practice in an adult MECC configuration, even for more obese patients, limiting artificial surface contact.
Seroprevalence of Toxoplasma gondii infection in dairy cattle in southern China
Authors: Zhou Dong-Hui , Zhao Fu-Rong , Lu Ping , Xia Hui-Yan , Xu Min-Jun , Yuan Li-Guo , Yan Chao , Huang Si-Yang , Li Shou-Jun , Zhu Xing-Quan
Published: March 2012

Background

As an obligate intracellular parasite, Toxoplasma gondii can infect humans and almost all warm-blooded animals. The consumption of raw or undercooked beef and milk is considered a risk for T. gondii infection in humans. However, little is known of T. gondii infection in dairy cattle in metropolitan Guangzhou, southern China. This study was performed to determine the seroprevalence of T. gondii in dairy cattle in Guangzhou, southern China.

Findings

Serum samples were collected from 350 dairy cattle on five farms in Guangzhou, China from 2009 to 2010, and all of the 350 serum samples were examined for specific antibodies to T. gondii by indirect hemagglutination antibody test (IHA). The overall seroprevalence of T. gondii in dairy cattle was 5.7% (20/350). Among these examined dairy cattle, dairy cattle which were < 6 year old or ≥ 5 year old had the highest seroprevalence of 12.5% followed by those dairy cattle which were < 5 year old or ≥ 4 year old (8%); dairy cattle with 3 pregnancies had the highest seroprevalence (11.5%), among the examined dairy cattle, although these differences were not statistically significant.

Conclusions

The results of the present survey indicate that T. gondii infection is prevalent in dairy cattle of all age ranges in Guangzhou, southern China, which may be a risk factor for human infection with T. gondii in this region.

Dong-Hui Zhou and Fu-Rong Zhao contributed equally.
Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis
Authors: Li Jie , Fadare Oluwole , Xiang Li , Kong Beihua , Zheng Wenxin
Published: March 2012

Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.
FAST: towards safe and effective subcutaneous immunotherapy of persistent life‐threatening food allergies
Authors: Zuidmeer‐Jongejan Laurian , Fernandez‐Rivas Montserrat , Poulsen Lars K , Neubauer Angela , Asturias Juan , Blom Lars , Boye Joyce , Bindslev‐Jensen Carsten , Clausen Michael , Ferrara Rosa , Garosi Paula , Huber Hans , Jensen Bettina M , Koppelman Stef , Kowalski Marek L , Lewandowska‐Polak Anna , Linhart Birgit , Maillere Bernard , Mari Adriano , Martinez Alberto , Mills Clare EN , Nicoletti Claudio , Opstelten Dirk‐Jan , Papadopoulos Nikos G , Portoles Antonio , Rigby Neil , Scala Enrico , Schnoor Heidi J , Sigurdardottir Sigurveig T , Stavroulakis George , Stolz Frank , Swoboda Ines , Valenta Rudolf , van den Hout Rob , Versteeg Serge A , Witten Marianne , van Ree Ronald
Published: March 2012

The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen‐specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side‐effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site‐directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre‐clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum‐absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double‐blind placebo‐controlled (DBPC) clinical trials, with the DBPC food challenge as primary read‐out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.
The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression
Authors: Frölich Daniela , Blaβfeld Daniela , Reiter Karin , Giesecke Claudia , Daridon Capucine , Mei Henrik E , Burmester Gerd R , Goldenberg David M , Salama Abdulagabar , Dörner Thomas
Published: March 2012

Introduction

Targeting CD74 as the invariant chain of major histocompatibility complexes (MHC) became possible by the availability of a specific humanized monoclonal antibody, milatuzumab, which is under investigation in patients with hematological neoplasms. CD74 has been reported to regulate chemo-attractant migration of macrophages and dendritic cells, while the role of CD74 on peripheral naïve and memory B cells also expressing CD74 remains unknown. Therefore, the current study addressed the influence of milatuzumab on B-cell proliferation, chemo-attractant migration, and adhesion molecule expression.

Methods

Surface expression of CD74 on CD27- naïve and CD27+ memory B cells as well as other peripheral blood mononuclear cells (PBMCs) obtained from normals, including the co-expression of CD44, CXCR4, and the adhesion molecules CD62L, β7-integrin, β1-integrin and CD9 were studied after binding of milatuzumab using multicolor flow cytometry. The influence of the antibody on B-cell proliferation and migration was analyzed in vitro in detail.

Results

In addition to monocytes, milatuzumab also specifically bound to human peripheral B cells, with a higher intensity on CD27+ memory versus CD27- naïve B cells. The antibody reduced B-cell proliferation significantly but moderately, induced enhanced spontaneous and CXCL12-dependent migration together with changes in the expression of adhesion molecules, CD44, β7-integrin and CD62L, mainly of CD27- naïve B cells. This was independent of macrophage migration-inhibitory factor as a ligand of CD74/CD44 complexes.

Conclusions

Milatuzumab leads to modestly reduced proliferation, alterations in migration, and adhesion molecule expression preferentially of CD27- naïve B cells. It thus may be a candidate antibody for the autoimmune disease therapy by modifying B cell functions.
Economic analyses of venous thromboembolism prevention strategies in hospitalized patients: a systematic review
Authors: Thirugnanam Subarna , Pinto Ruxandra , Cook Deborah J , Geerts William H , Fowler Robert A
Published: March 2012

Introduction

Despite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship.

Methods

We searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy.

Results

From 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored.

Conclusion

Low-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous thromboembolism prevention in hospitalized patients. Approximately two thirds of evaluations were supported by the manufacturer of the new agent; such drugs were likely to be reported as economically favorable.
The discovery of the Maria deposit, Mexico
Authors: Visser Syd J. , Lajoie Jules J.
Published: March 2012

The Maria deposit is about 10 km northwest of the town of Cananea, Sonora, Mexico, and about 160 km south of Tucson, USA. Cananea, a historic mining district dating from the 19th century, hosts one of the largest porphyry copper deposits in the world (>30 billion pounds Cu) (Titley, 1982, and Pierce et al., 1995). Mineralization is in an area of about 40 × 4 km and follows a northwest-striking belt of Laramide quartz feldspar porphyry stocks that includes significant historic production from related skarn deposits in carbonate rocks. Porphyry-related ores in the district occur in three types: supergene-enriched standard porphyry-style mineralization with grade in the order of 0.7% Cu, a number of large porphyry copper-related higher-grade (1–2% Cu) standard hydrothermal breccia pipes, and the unusual high grade (∼7% Cu) large La Colorada brecciated massive sulfide/silicate pegmatite ore body.
Passive seismic tomography for three-dimensional time-lapse imaging of mining-induced rock mass changes
Authors: Westman Erik , Luxbacher K. , Schafrik S.
Published: March 2012

Progression of an immature block cave in proximity to a mature sublevel cave was monitored over an 18-month period using double-difference tomography. This method utilizes existing microseismic data to generate time-lapse images of seismic wave velocity changes within the rock mass. The velocity changes are caused by damage zones forming or local high-stress concentrations. In this study, images were generated on monthly intervals. An average of 2000 microseismic events recorded by 25 stations were used to generate each image. Results showed a development of the initial undercut followed by the growing cave and interaction with the adjacent sublevel cave. The goal of the research is to provide a tool that can augment both numerical modeling results and underground geotechnical measurements to allow the mine operator to produce in the safest and most efficient manner possible.
Distinguishing adolescents who think about self-harm from those who engage in self-harm
Authors: O'Connor Rory C. , Rasmussen Susan , Hawton Keith
Published: March 2012

Background

Adolescent self-harm is a major public health concern, yet little is known about the factors that distinguish adolescents who think about self-harm but do not act on these thoughts from those who act on such thoughts.

Aims

Within a new theoretical model, the integrated motivational–volitional model, we investigated factors associated with adolescents having thoughts of self-harm (ideators)v.those associated with self-harm enaction (enactors).

Method

Observational study of school pupils employing an anonymous self-report survey to compare three groups of adolescents: self-harm enactors (n= 628)v.self-harm ideators (n= 675)v.those without any self-harm history (n= 4219).

Results

Enactors differed from ideators on all of the volitional factors. Relative to ideators, enactors were more likely to have a family member/close friend who had self-harmed, more likely to think that their peers engaged in self-harm and they were more impulsive than the ideators. Enactors also reported more life stress than ideators. Conversely, the two self-harm groups did not differ on any of the variables associated with the development of self-harm thoughts.

Conclusions

As more adolescents think about self-harm than engage in it, a better understanding of the factors that govern behavioural enaction is crucial in the effective assessment of the risk of self-harm.
Myocardial infarction and generalised anxiety disorder: 10-year follow-up
Authors: Roest Annelieke M. , Zuidersma Marij , de Jonge Peter
Published: March 2012

Background

Few studies have addressed the relationship between generalised anxiety disorder and cardiovascular prognosis using a diagnostic interview.

Aims

To assess the association between generalised anxiety disorder and adverse outcomes in patients with myocardial infarction.

Method

Patients with acute myocardial infarction (n = 438) were recruited between 1997 and 2000 and were followed up until 2007. Current generalised anxiety disorder and post-myocardial infarction depression were assessed with the Composite International Diagnostic Interview. The end-point consisted of all-cause mortality and cardiovascular-related readmissions.

Results

During the follow-up period, 198 patients had an adverse event. Generalised anxiety disorder was associated with an increased rate of adverse events after adjustment for age and gender (hazard ratio: 1.94; 95% confidence interval: 1.14–3.30; P = 0.01). Additional adjustment for measures of cardiac disease severity and depression did not change the results.

Conclusions

Generalised anxiety disorder was associated with an almost twofold increased risk of adverse outcomes independent demographic and clinical variables and depression.
Pax6 Is Crucial for β-Cell Function, Insulin Biosynthesis, and Glucose-Induced Insulin Secretion
Authors: Gosmain Yvan , Katz Liora S. , Masson Mounia Heddad , Cheyssac Claire , Poisson Caroline , Philippe Jacques
Published: March 2012

The Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and a drastic decrease of insulin-positive cell number. Our aim was to better define the β-cell Pax6 transcriptional network and thus provide further information concerning the role of Pax6 in β-cell function. We developed a Pax6-deficient model in rat primary β-cells with specific small interfering RNA leading to a 75% knockdown of Pax6 expression. Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. Furthermore, we demonstrated that Pax6 directly binds and activates specific elements on the promoter region of these genes. We also demonstrated that Pax6 knockdown led to decreases in insulin cell content, in insulin processing, and a specific defect of glucose-induced insulin secretion as well as a significant reduction of GLP-1 action in primary β-cells. Our results strongly suggest that Pax6 is crucial for β-cells through transcriptional control of key genes coding for proteins that are involved in insulin biosynthesis and secretion as well as glucose and incretin actions on β-cells. We provide further evidence that Pax6 represents a key element of mature β-cell function.
Clinical outcomes after percutaneous biliary interventions in patients with malignant biliary obstruction caused by metastatic gastric cancer
Authors: Gwon Dong II , Ko Gi-Young , Sung Kyu-Bo , Yoon Hyun-Ki , Kim Kyung-Ah , Kim Young Jun , Kim Tae Hwan , Lee Woong Hee
Published: March 2012

Background

No report has appeared on the histologic characteristics as influencing factors associated with clinical outcomes and survival of patients who underwent percutaneous biliary interventions to treat malignant biliary obstruction caused by metastatic gastric cancer.

Purpose

To investigate the clinical outcomes after percutaneous biliary interventions in patients with malignant biliary obstruction caused by metastatic gastric cancer and to identify prognostic factors associated with clinical outcomes.

Material and Methods

We retrospectively assessed 117 patients who underwent percutaneous transhepatic biliary drainage (PTBD) between January 2005 and December 2009, for treatment of malignant biliary obstructions caused by metastatic gastric cancer. Of these 117 patients, 54 subsequently underwent metallic stent placement.

Results

The technical success rates of PTBD and metallic stent placement were 100% and 100%, respectively. Self-limiting hemobilia after PTBD occurred in eight (7%) patients, and self-limiting hemobilia ( n = 4) and acute pancreatitis ( n = 3) after stent placement occurred in seven (13%) patients. Successful drainage was achieved in 105 (90%) of the 117 patients who underwent PTBD and in 49 (91%) of 54 patients who underwent metallic stent placement. Multiple Cox's regression analysis showed that the histology of primary gastric cancer ( P = 0.011), serum bilirubin after PTBD ( P = 0.002) and stenting ( P = 0.017), and chemotherapy after PTBD ( P < 0.001) and stenting ( P = 0.033) were independent predictors of survival.

Conclusion

PTBD and subsequent metallic stent placement were safe and effective methods for palliative treatment in patients with malignant biliary obstruction caused by metastatic gastric cancer. Patients with a differentiated histology of primary gastric cancer and serum bilirubin level ≤2 mg/dl after PTBD are probably the best candidates for treatment with a combination of metallic stent placement and chemotherapy.
Should Rheumatologists be Managing Fibromyalgia?
Authors: Larkin J
Published: March 2012

Fibromyalgia has always struggled to be taken seriously. The vague mixture of aches, pains, stiffness and fatigue with no clear clinical or investigational findings has led many to doubt its very existence. Evidence is accumulating, however, of demonstrable abnormalities of pain processing and psychosocial factors in fibromyalgia subjects. These may ‘prove’ its existence, but do they suggest it is rheumatological?
Perianal Actinomycosis: A Case Study of this Rare Infection Associated with Nicorandil Usage
Authors: Ablett D J , Wylie J R , Berlansky M S
Published: March 2012

Perianal actinomycosis infection is a very rare occurrence and is challenging to diagnose. Nicorandil is a potassium channel agonist, which is used in the treatment of ischaemic heart disease. Its usage is associated with perianal ulceration and delayed surgical wound healing. We report a case of actinomycosis complicating a chronic perianal ulcer, which was associated with long-term nicorandil usage. It raised the suspicion of malignancy and required over six months of antimicrobial treatment to achieve satisfactory healing. Perianal actinomycosis results in chronic infection which spreads across tissue planes and can resemble an ulcerated malignancy. Nicorandil usage can result in perianal ulceration and produces conditions which are conducive to actinomycosis infection. In such cases, nicorandil therapy should be discontinued, if possible, and long-term systemic antibiotics form the mainstay of treatment.
Primary Necrotizing Fasciitis of the Breast: A Case Report and Review of the Literature
Authors: Ablett D J , Bakker-Dyos J , Rainey J B
Published: March 2012

Primary necrotizing fasciitis of the breast is extremely rare. We describe a case of a 51-year-old diabetic smoker who presented with primary necrotizing fasciitis of the breast, with signs of severe systemic sepsis. She required intravenous antibiotics, radical emergency surgery, intensive care treatment and inotropic support. After daily wound inspections and changes of dressings, the wound was amenable to delayed primary closure on day 6. We describe this case in detail and review the literature on this extremely rare, but potentially fatal, infection.
Alcohol and Drug Misuse, Risk of Re-admission to a General Hospital and Psychiatric Contact
Authors: Goldbeck R , Asif M , Sanderson M , Farquharson C
Published: March 2012

Patients with physical problems related to the use of alcohol or drugs often present to general hospitals in an unplanned, emergency fashion. In 2005, the Kerr report concluded that fundamental changes were needed in our approach, shifting the emphasis from a reactive to a more proactive, prevention-based model in the treatment of acute medical conditions. We studied patients who had at least one alcoholor drug-related emergency admission, whose most recent admission was to Aberdeen Royal Infirmary and who, using the Scottish Patients at Risk of Re-admission and Admission (SPARRA) All Ages Tool, were thought to be at high risk of further emergency admission. We examined data sets derived from the National Health Service National Services Scotland Information Services Division, a Liaison Psychiatry database, data from the local psychiatric Patient Information Management System and data collected by the hospital alcohol liaison nurse to examine this group of patients further and consider the scope for any future intervention. Patients who have an alcoholor drug-related emergency admission to the general hospital are at increased risk of re-admission. A substantial proportion of these patients has come into contact with the psychiatric services, often attracting a substance misuse and/or personality disorder diagnosis. A significant proportion also presents in the context of self-harm. In conclusion, this group of frequent hospital attenders may be difficult to engage but may benefit from more proactive intervention, a more joined-up management approach and the development of an enhanced general hospital alcohol liaison service.
CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome
Authors: Query Charles C. , Konarska Maria M.
Published: March 2012

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3′ splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast.
Exact Solution of Large-Scale Hub Location Problems with Multiple Capacity Levels
Authors: Contreras Ivan , Cordeau Jean-François , Laporte Gilbert
Published: March 2012

This paper presents an extension of the classical capacitated hub location problem with multiple assignments in which the amount of capacity installed at the hubs is part of the decision process. An exact algorithm based on a Benders decomposition of a strong path-based formulation is proposed to solve large-scale instances of two variants of the problem: the splittable and nonsplittable commodities cases. The standard decomposition algorithm is enhanced through the inclusion of features such as the generation of strong optimality cuts and the integration of reduction tests. Given that in the nonsplittable case the resulting subproblem is an integer program, we develop an efficient enumeration algorithm. Extensive computational experiments are performed to evaluate the efficiency and robustness of the proposed algorithms. Computational results obtained on benchmark instances with up to 300 nodes and five capacity levels confirm their efficiency.
Out of sight, out of mind: the exploitation of migrant workers in 21st-century Britain
Authors: Wilkinson Mick
Published: March 2012

Over the past decade, a team at the University of Hull has undertaken four separate but linked research projects investigating the working and living conditions of migrant workers in the United Kingdom (UK).1 Those studies drew on the experiences of a broad range of service providers – national and local, statutory and voluntary – all of whom had regular interaction with vulnerable workers or their advocates, together with the testimonies of several hundred migrant workers who had themselves experienced or witnessed employment (and related accommodation) exploitation in gangmaster UK. The findings, summarised here, are an indictment of British government indifference to the exploitation of the migrant workforce.
Reliance on migrant labour: inevitability or policy choice?
Authors: Anderson Bridget , Ruhs Martin
Published: March 2012

This article discusses employer demand for migrant labour. We argue that the UK's growing reliance on migrant workers cannot simply be explained by lax immigration controls or migrants’ superior ‘work ethic’. It arises from the complex interactions between institutions, public policies and social relations. A wide range of public policies have contributed to a growing demand for migrant workers in the UK
Understanding Universal Credit
Authors: Royston Sam
Published: March 2012

Universal Credit is due to be introduced for new claimants from October 2013. In what is arguably the biggest overhaul of the welfare system in the United Kingdom (UK) since the Beveridge reforms of the 1940s, Income Support, Income based Jobseeker's Allowance, income based Employment and Support Allowance, Housing Benefit and Working and Child Tax Credits are all to be abolished and replaced with a single payment. Universal Credit presents the potential for a much simpler system with improved work incentives for many. However, perhaps inevitably with such a fundamental overhaul, the proposals for the credit as they stand also have a number of problems. This article identifies a number of these issues, and presents policy recommendations to help ensure the development of a reformed welfare system that works for all.
CouchSurfing as a spatial practice: Accessing and producing xenotopos
Authors: Zuev Dennis
Published: March 2012

The aim of this study is to analyse the production of space in the CouchSurfing hospitality network in Russia. The article proposes the notion of xenotopos, which literally means 'the place of strangers', in order to capture the relational dynamics of host and guest interactions and
their co-present experience of space, time and life rhythms. The article examines the interaction between the spatial knowledge of the host and of the guest in order to see how the sharing of this knowledge affects the spatial trajectory of the guest. The article also considers the potential
applicability of the concept of rhythm in the analysis of CouchSurfing as a spatial practice. The findings suggest that CouchSurfing allows users to open up new spaces of hospitality situated away from conventional tourist circuits by accessing local knowledge and grasping local life rhythms,
both of which become essential intangible aspects of the CouchSurfing experience.
Technologies of hospitality: How planned encounters develop between strangers
Authors: Bialski Paula
Published: March 2012

New technologies in use today like CouchSurfing.com are allowing people to create planned encounters, en masse, between other strangers. These 'technologies of hospitality' are producing new rules of engagement, and new relationships that blur the boundaries between friend, acquaintance,
stranger and enemy – boundaries that are yet to be defined. This article will show that while mobility inevitably causes strangers to collide and interact, certain technologies of hospitality in use today create conditions for strangers to meet one another and engage in acts of hospitality
– moments of intimacy, closeness or mutual understanding. This article outlines the process by which two strangers become close using one such technology: CouchSurfing.org. While such encounters foster trust, mutual learning and 'personal growth', closeness is not always altruistic and
technologies of hospitality also allow people involved to exert their status and power during interaction, creating moments of tension, awkwardness or distrust. Using multi-method ethnography, this article provides an in-depth account of these technologies of hospitality, focusing on the relationships
being created as well as the problems that arise for the way in which we define friendship and closeness today.
CouchSurfing and authenticity: Notes towards an understanding of an emerging phenomenon
Authors: Steylaerts Vicky , Dubhghaill Sean O’
Published: March 2012

The work presented here first outlines and then theorizes the emergence of CouchSurfing as a trend, as well as an allegedly more authentic form of travel. This article attempts to trace a line from globalization to authenticity, navigating the delicate binaries evident in current tourism
research in an effort to fuse the macro-level theorizing to the individuated reflections by CouchSurfers on the phenomenon itself. We discuss homogenization, positive and negative experiences, and how participants individuate their CouchSurfing experience, so that it is uniquely theirs. Examining
circumstances and experiences from the perspective of CouchSurfers themselves, an endeavour undertaken too sparingly, we consider the presence of a latent paradox, concerning the degree to which an individual can individuate his or her CouchSurfing experience, within the host/guest dichotomy.
Global concept, local practice: Taiwanese experience of CouchSurfing
Authors: Chen De-Jung
Published: March 2012

Hospitality exchange tourism is a new type of niche tourism, which is highly dependent on the Internet. Through participating in global hospitality exchange networks, such as CouchSurfing, tourists can meet local people who are willing to offer free accommodation, and hosts can also
meet people around the world by hosting them. CouchSurfing works as a system of reciprocity, in which hospitality as well as cultures is exchanged between hosts and surfers. Through hospitality sharing and cross-cultural interactions, a global community with diverse cultures is envisaged in
CouchSurfing. Although CouchSurfing is global in its scope, it is locally practiced in different ways by different cultures. The meaning of CouchSurfing is negotiated by surfers and hosts who both participate in it, and the reciprocal system of CouchSurfing seems to be more complicated when
different cultures are involved. Based on Taiwanese experiences of CouchSurfing, this study introduces a non-western perspective on CouchSurfing and has a dialogue with prior research about CouchSurfing that has tended to focus on western experiences. Qualitative methods, including participatory
observation and qualitative interviews, are adopted in this study to explore how CouchSurfing is practiced in non-western society.