bluuebunny/crossref_metadata_2025 huggingface dataset:
Politically Connected Firms and Earnings Informativeness in the Controlling versus Minority Shareholders Context:European Evidence
Authors: Bona‐Sánchez Carolina , Pérez‐Alemán Jerónimo , Santana‐Martín Domingo Javier
Published: March 2014

Manuscript Type

Empirical

Research Question/Issue

Focusing on an environment where ownership concentration is prevalent and where the presence of politically connected directors on the board is the natural form of political connection, we analyze the effect of political connections on earnings informativeness. We also examine a question that has not been considered in previous research, namely, the impact of the level of divergence between the dominant owner's voting and cash flow rights on earnings informativeness for politically connected firms.

Research Findings/Insights

We find that the presence of politicians on the board negatively affects earnings informativeness. We also find a positive impact of the divergence between the dominant owner's voting and cash flow rights on the informativeness of accounting earnings in politically connected firms.

Theoretical/Academic Implications

We show that the relationship between political ties and earnings informativeness is explained by an information effect, whereby politicians and shareholders are interested in providing as little information to the market as possible in order to protect political ties from public scrutiny and prevent the leakage of competitive advantages to competitors. Additionally, we show that the positive effect of divergence between the dominant owner's voting and cash flow rights on earnings informativeness in firms that belong to a pyramid is explained both by an alignment effect, whereby political connections promote transparency, as well as by a stewardship effect, whereby the ultimate owner of the pyramid, acting as a steward, places politicians on the board to increase the firm's reputation and reports earnings in good faith.

Practitioner/Policy Implications

The results of our study may be useful to regulators interested in increasing transparency in order to promote a more efficient allocation of resources. In particular, the results suggest that in countries where recent reforms aim to improve investor protection and market confidence, regulators should encourage the disclosure of firm political ties. The results of our study may also be useful to investors, financial analysts and auditors, as they highlight the importance of considering specific features of the corporate governance system when assessing the credibility of accounting information.
Preoperative Cylex assay predicts rejection risk in patients with kidney transplant
Authors: Myslik Frank , House Andrew A. , Yanko Daniel , Warren Jeff , Caumartin Yves , Rehman Faisal , Jevnikar Anthony M. , Stitt Larry , Luke Patrick P.
Published: March 2014

Introduction and Objectives

The ImmuKnow assay measures cell‐mediated immunity by quantifying ATP release from CD4+ T‐cells in peripheral blood. Herein, we hypothesized that this assay could predict complications associated with over‐/under‐immunosuppression in patients with kidney transplant (KT).

Methods

Sixty‐seven patients undergoing KT were recruited prospectively and had ATP levels measured preoperatively, and at specified intervals over two months. Clinicians were blinded to ATP levels. Clinical events including rejection and infection/cancer were documented with a median follow‐up of 21 months. Parameters including absolute ATP levels and changes in ATP patterns (slopes, delta) were analyzed. Association between ATP parameters and clinical outcomes was compared using the likelihood‐ratio test and Kaplan–Meier curves.

Results

Absolute ATP values postoperatively had poor predictive value with regard to rejection or infection/malignancy. As well, changes in ATP values were poorly associated with complications. Importantly, patients with pre‐transplant ATP values <300 ng/mL had significantly less rejection episodes vs. those with ATP values >300 ng/mL (p < 0.0001).

Conclusions

For the first time, we have evidence that a preoperative ImmuKnow level can stratify patients with KT into low/high risk groups for rejection. Future studies used to assess the utility of this assay to design individualized immunosuppressive regimens are required.
The big night out: What happens on the most recent heavy drinking occasion among young Victorian risky drinkers?
Authors: Dietze Paul M. , Livingston Michael , Callinan Sarah , Room Robin
Published: March 2014

Introduction and Aims

In spite of the major focus on risky, single‐occasion drinking by young people in Australia, little is known about the specific circumstances of risky drinking occasions. This study examines drinking behaviours and drinking contexts for the most recent risky, single‐occasion drinking episode in a representative sample of young risky drinkers in Victoria, Australia.

Design and Methods

A representative sample of 802 young risky drinkers was recruited across metropolitan Melbourne and surveyed about their drinking and related behaviours. Specific questions focused on participants' most recent high‐risk (>10 Australian standard drinks for males, >7 Australian standard drinks for females) drinking occasion in terms of self‐reported amount drunk, alcohol expenditure (including buying rounds) and drinking partners for up to 10 different drinking settings.

Results

Participants reported drinking a mean of 13 Australian standard drinks on their last episode of risky, single‐occasion drinking; for half of the participants, this occurred less than 20 days prior to being surveyed. The majority (62%) of risky single occasion drinking sessions commenced at private homes in the company of close friends (81%). Around 40% of the sample reported going to one (42%) or two (37%) drinking locations, and only 5% reported going to more than three drinking locations.

Discussion and Conclusions

Contrary to public portrayals, a significant amount of risky drinking by young people occurs in private settings. These contexts are rarely mentioned except in relation to underage drinking. Further work is needed to understand how these drinking behaviours and contexts link to harm. [Dietze PM, Livingston M, Callinan S, Room R. The big night out: what happens on the most recent heavy drinking occasion among young Victorian risky drinkers? Drug Alcohol Rev 2014;33:346–353]
Research in practice: The impact of interferon‐α therapy on immune tolerance
Authors: Raker Verena , Steinbrink Kerstin
Published: March 2014

Interferon‐α (IFN‐α) is the only drug approved for adjuvant therapy of malignant melanoma and is also used in the treatment of hematological and solid tumors. Along with its proven clinical efficacy, IFN‐α produces several side effects, particularly with regard to autoimmune disorders. Curious about symptoms of autoimmunity during IFN‐α therapy, we asked whether IFN‐α directly impacts on immune tolerance. We found that IFN‐α does alter the function of tolerogenic dendritic cells (DC) as well as of induced and naturally occurring T‐regulatory cells (nTregs). IFN‐α blocks the tolerogenic phenotype of DC by inducing maturation and thus preventing the induction of inducible Tregs by DC. It also has direct effects on nTregs. IFN‐α reduces cAMP in Tregs via ERK/phosphodiesterase‐mediated pathways. Since cAMP is essentially involved in suppression by nTregs, the IFN‐α‐dependent reduction of cAMP levels abolishes the suppressive capacity of nTregs. Therefore, Tregs are incapable of suppressing the activity of effector T cells and natural killer cells, resulting in tumor rejection. Thus, IFN‐α overcomes immunological tolerance processes, leading to an improved immunostimulation and efficient tumor rejection, but also increases the risk of autoimmunity.
Azacitidine and low‐dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts – a retrospective single‐center experience
Authors: Radujkovic Aleksandar , Dietrich Sascha , Bochtler Tilmann , Krämer Alwin , Schöning Tilman , Ho Anthony D. , Dreger Peter , Luft Thomas
Published: March 2014

We retrospectively analyzed and compared the efficacy and toxicity of azacitidine (AZA) and low‐dose cytarabine (LD‐Ara‐C) in 65 palliative patients with acute myeloid leukemia (AML) showing high bone marrow blast counts (≥30%) before start of treatment. Twenty‐seven and 38 patients received AZA and LD‐Ara‐C, respectively. The median patient age was 71 yr. Patient and disease characteristics did not differ between the treatment groups, except for BM blast counts, and peripheral leukocyte and blast counts which were significantly higher in the LD‐Ara‐C group. AZA and LD‐Ara‐C were first‐line treatment in 12 (44%) and 17 patients (45%), respectively. Response and hematologic improvement rates were low and similar in both treatment groups. In both treatment groups, most common non‐hematologic toxicities included febrile neutropenia, pneumonia, and bleedings without significant differences regarding frequencies. Estimated 1‐yr survival rates were 15% (95% CI 8–22) and 13% (95% CI 7–19) in the AZA and LD‐Ara‐C groups, respectively, without statistically significant difference. In multivariate analysis (n = 65), previous treatment (HR 2.27, 95% CI 1.00–5.22, P = 0.05) and adverse cytogenetics (HR 2.50, 95% CI 1.20–5.22, P = 0.02) were independent predictors of poor survival. In our center and within the limitations of a retrospective study, both treatment regimens showed similar but limited efficacy in palliative patients with AML and high BM blast counts.
The bone marrow hematopoietic microenvironment is impaired in iron‐overloaded mice
Authors: Okabe Hiroshi , Suzuki Takahiro , Uehara Eisuke , Ueda Masuzu , Nagai Tadashi , Ozawa Keiya
Published: March 2014

Objectives

Increasing numbers of reports have described hematopoietic improvement after iron chelation therapy in iron‐overloaded patients. These observations indicate that excess iron could affect hematopoiesis unfavorably. To investigate how excess iron affects hematopoiesis in vivo, we generated iron‐overloaded mice and examined hematopoietic parameters in these mice.

Methods

We generated iron‐overloaded mice by injecting 200 mg of iron dextran into C57BL/6J mice, and immature hematopoietic cells in the bone marrow were evaluated by flow cytometric analyses, colony‐forming assays, and bone marrow transplantation analyses. We also examined changes in molecular profiles of the hematopoietic microenvironment.

Results and Conclusions

Iron‐overloaded (IO) mice did not show significant defects in the hematopoietic data of the peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution, which indicates that excess iron impacts the hematopoietic microenvironment negatively. Microarray and quantitative RT‐PCR analyses on the bone marrow stromal cells demonstrated remarkably reduced expression of CXCL12, VCAM‐1, Kit‐ligand, and IGF‐1 in the iron‐overloaded mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and increased oxidative stress was observed in the IO bone marrow and liver. Consequently, our findings indicate that excess iron can damage bone marrow stromal cells and other vital organs, disrupting hematopoiesis presumably by increased oxidative stress.
The role of the substantia nigra in posture control
Authors: Barter Joseph W. , Castro Stephen , Sukharnikova Tatyana , Rossi Mark A. , Yin Henry H.
Published: March 2014

Disorders implicating the basal ganglia are often characterized by postural deficits, but little is known about the role of the basal ganglia in posture control. Using wireless multi‐electrode recording, we measured single unit activity from GABAergic and dopaminergic neurons in the substantia nigra as unrestrained mice stood on an elevated platform while introducing continuous postural disturbances in the roll plane. We found two major types of neurons – those activated by tilt to the left side of the body and suppressed by tilt to the right side, and others activated by tilt to the right side and suppressed by tilt to the left side. Contrary to the prevailing view that the basal ganglia output from the substantia nigra pars reticulata either inhibits or disinhibits downstream structures in an all or none fashion, we showed that it continuously sends anti‐phase signals to their downstream targets. We also demonstrated for the first time that nigrostriatal dopaminergic transmission is modulated by postural disturbances.
Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats
Authors: Cordeiro Karina Kohn , Cordeiro Joacir Graciolli , Furlanetti Luciano Lopes , Garcia Salazar Joanna Alejandra , Tenório Sérgio Bernardo , Winkler Christian , Döbrössy Máté Daniel , Nikkhah Guido
Published: March 2014

Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue‐restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6‐hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB‐lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6‐fold compared with the control grafted‐only group. Moreover, performance on the drug‐induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI‐lesioned group to a significantly greater extent than the grafted‐only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.
Low free testosterone is associated with loss of appendicular muscle mass in Japanese community‐dwelling women
Authors: Yuki Atsumu , Ando Fujiko , Otsuka Rei , Shimokata Hiroshi
Published: March 2014

Aim

Sarcopenia accelerates frailty syndrome, and adversely affects activities of daily living and quality of life. The aim of the present study was to assess longitudinal relationships between baseline androgen and muscle mass changes in Japanese women.

Methods

Data were collected from 539 community‐dwelling, Japanese women aged 40–79 years at baseline who participated in both baseline and follow‐up examinations of a longitudinal study of aging (mean duration 8.3 years). Appendicular skeletal muscle mass was measured with dual‐energy X‐ray absorptiometry at baseline and follow‐up examinations. The cut‐off point for sarcopenia was a skeletal muscle index (appendicular skeletal muscle mass/height2) <5.46 kg/m2. Participants with sarcopenia at baseline were excluded. Thus, 430 women were included. Total testosterone, free testosterone and dehydroepiandrosterone‐sulphate were measured by radioimmunoassay at baseline. The androgens were categorized into three groups by serum levels. Multiple logistic regression models were fit to determine the associations between androgens and sarcopenia while controlling for baseline age, body mass index, leisure‐time physical activity, nutritional intakes (total energy, total protein, vitamin D), serum C‐reactive protein levels, medical histories (heart disease, osteoporosis, rheumatoid arthritis), menopause and smoking habit.

Results

The fully adjusted odds ratio of sarcopenia for the low‐free testosterone group (<0.7 pg/mL) compared with the high‐free testosterone group (≥1.2 pg/mL) was 3.59 (95% confidence interval 1.25–10.34). Sarcopenia was not significantly related to total testosterone or dehydroepiandrosterone‐sulphate.

Conclusion

A low‐free testosterone level appears to be a significant predictor of the risk for loss of appendicular muscle in Japanese women. Geriatr Gerontol Int 2015; 15 326–333.
Mental Disorder, Criminality and the Literary Imagination
Authors: Prins Herschel
Published: March 2014

This contribution attempts to explore the use of a variety of literary sources as aids or ‘prompts’ to understanding those offenders and offender‐patients whose mental states often raise considerable anxieties in those charged with their management. The word ‘prompt’ is borrowed from the work of my friend, the late doctor Murray Cox, and his co‐worker Alice Theilgaard in their seminal work Shakespeare as Prompter (1994). The author of the present article hopes that its content will enable readers to focus more clearly on why we sometimes fail our offenders and offender‐patients; in particular, through the mechanism of denial. The use of dramatic presentation when proffered with a unique blend of force and sensitivity can permit us to view puzzlement and horror from a safe distance and, at the same time, encourage us to increase our empathic understanding and professional practice. Most of the examples cited are brief allusions but, because her history is so compellingly applicable to our concerns in the present contribution, the ‘case’ of Lady Macbeth is considered in more detail. Finally, I would note some very wise words by Cox and Theilgaard (1994) in a caveat note to the reader: ‘Should the focus on therapy ever become occluded by preoccupation with poetic association, clinical skills would be diminished, distraction ensue and therapeutic contact deteriorate’ (not numbered). In the material that follows readers should bear such a cautionary note in mind.
ICSH guidelines for the verification and performance of automated cell counters for body fluids
Authors: Bourner G. , De la Salle B. , George T. , Tabe Y. , Baum H. , Culp N. , Keng T. B. ,   the International Committee for Standardization in Hematology (ICSH)
Published: March 2014

One of the many challenges facing laboratories is the verification of their automated Complete Blood Count cell counters for the enumeration of body fluids. These analyzers offer improved accuracy, precision, and efficiency in performing the enumeration of cells compared with manual methods. A patterns of practice survey was distributed to laboratories that participate in proficiency testing in Ontario, Canada, the United States, the United Kingdom, and Japan to determine the number of laboratories that are testing body fluids on automated analyzers and the performance specifications that were performed. Based on the results of this questionnaire, an International Working Group for the Verification and Performance of Automated Cell Counters for Body Fluids was formed by the International Council for Standardization in Hematology (ICSH) to prepare a set of guidelines to help laboratories plan and execute the verification of their automated cell counters to provide accurate and reliable results for automated body fluid counts. These guidelines were discussed at the ICSH General Assemblies and reviewed by an international panel of experts to achieve further consensus.
Migration Policy and Development in Chile
Authors: Doña Reveco Cristián , Mullan Brendan
Published: March 2014

Current and prospective migration law and policy in Chile does not adequately incorporate the causes, content, and consequences of international migration to and from Chile. We describe and examine migration in‐flows, out‐flows, migration‐related policies, and how those policies drive, and are driven by, notions of development in Chile. We explore contradictions in Chilean nascent migration policy currently under legislative review. We argue that it is imperative that migration, migration policy, and their relationship to development be discussed inclusively and transparently and be explicitly incorporated into the Chilean government's nascent migration and development legal policies and frameworks.
Evaluation of peroxisome proliferator‐activated receptor agonists on interleukin‐5‐induced eosinophil differentiation
Authors: Smith Steven G. , Hill Mike , Oliveria John‐Paul , Watson Brittany M. , Baatjes Adrian J. , Dua Benny , Howie Karen , Campbell Heather , Watson Rick M. , Sehmi Roma , Gauvreau Gail M.
Published: March 2014

Peroxisome proliferator‐activated receptor (PPAR) agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists has been shown to inhibit airway eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including attenuated generation of chemoattractants (e.g. eotaxin) and decreased eosinophil migrational responses. In addition, studies report that PPAR agonists can inhibit the differentiation of several cell types. To date, no studies have examined the effects of PPAR agonists on interleukin‐5 (IL‐5) ‐induced eosinophil differentiation from haemopoietic progenitor cells. Non‐adherent mononuclear cells or CD34+ cells isolated from the peripheral blood of allergic subjects were grown for 2 weeks in Methocult® cultures with IL‐5 (10 ng/ml) and IL‐3 (25 ng/ml) in the presence of 1–1000 nm PPARα agonist (GW9578), PPARβ/δ agonist (GW501516), PPARγ agonist (rosiglitazone) or diluent. The number of eosinophil/basophil colony‐forming units (Eo/B CFU) was quantified by light microscopy. The signalling mechanism involved was assessed by phosphoflow. Blood‐extracted CD34+ cells cultured with IL‐5 or IL‐5 + IL‐3 formed Eo/B CFU, which were significantly inhibited by rosiglitazone (100 nm, P < 0·01) but not GW9578 or GW501516. In addition, rosglitazone significantly inhibited IL‐5‐induced phosphorylation of extracellular signal‐regulated kinase 1/2. We observed an inhibitory effect of rosiglitazone on eosinophil differentiation in vitro, mediated by attenuation of the extracellular signal‐regulated kinase 1/2 signalling pathway. These findings indicate that the PPARγ agonist can attenuate tissue eosinophilia by interfering with local differentiative responses.
Does Job Satisfaction Vary with Sexual Orientation?
Authors: Leppel Karen
Published: March 2014

The results of this study, which uses data from the 2007–2008 Canadian Community Health Survey, suggest that job satisfaction may vary with sexual orientation. Probit regression analysis indicated that compared to heterosexuals, gay men and lesbians tended to be less satisfied with their jobs. Bisexuals appear to be more satisfied. Additional research is needed to corroborate the findings and the reasons for the differences.
Supercenters, Unionized Labor, and Performance in Food Retail
Authors: Volpe Richard
Published: March 2014

This study examines the impact of unionized labor on supermarket performance, as measured by profit and sales, accounting for the competitive presence of supercenters. The results confirm prior research that shows that supercenters have negative effects on supermarket performance. Unionized supermarkets generally outperform nonunionized supermarkets. However this effect disappears when accounting for supercenters, largely because unionized stores are less likely to compete with supercenters. I find no evidence for a significant union effect on supermarket performance. The deleterious effects of supercenters are stronger for unionized stores. Unionized supermarkets utilize less full‐time labor and more labor‐saving technology than do nonunionized ones.
Time‐varying Integration in European Government Bond Markets
Authors: Abad Pilar , Chuliá Helena , Gómez‐Puig Marta
Published: March 2014

Bond market integration clearly changes in response to economic and financial conditions, since the level of risk aversion changes and investors require time‐varying compensation for accepting a risky payoff from financial assets. In this paper we examine the dynamic behaviour of European Government bond market integration using an asset pricing model based on that of Bekaert and Harvey (). Our sample period begins in 2004, after a period of calm and tranquillity, and ends in 2009, with a significant widening of sovereign bond spreads. Our results show evidence of time‐varying level of integration for all European countries and suggest that, from the beginning of the financial market tensions in August 2007, markets moved towards higher segmentation, and the differentiation of country risk factors increased substantially across countries. However, the impact of the financial and economic crisis has been much more harmful for EMU members’ sovereign bond markets, since it has prompted an important backward step in their integration process.
Pyrethroid insecticide exposure and reproductive hormone levels in healthy Japanese male subjects
Authors: Yoshinaga J. , Imai K. , Shiraishi H. , Nozawa S. , Yoshiike M. , Mieno M. N. , Andersson A.‐M. , Iwamoto T.
Published: March 2014

The associations between serum levels of reproductive hormones (follicle‐stimulating hormone, luteinizing hormone, testosterone, sex hormone‐binding globulin, inhibin B and calculated free testosterone) and urinary metabolite concentration of pyrethroid insecticides [3‐phenoxybenzoic acid (3‐PBA)] were explored in 322 male university students in suburban Tokyo. The subjects constituted part of a large cross‐sectional survey on the reference value of semen quality of Japanese men. Urinary 3‐PBA was detectable in 91% of the subjects demonstrating ubiquitous exposure among the general population. However, there were no associations between urinary 3‐PBA and serum hormone levels. This result was inconsistent with those reported in China and the USA for subjects who had similar levels of urinary 3‐PBA to the present subjects. One of the possible reasons of the inconsistency might be different composition of pyrethroid insecticides to which the subjects were exposed; 3‐PBA is a common metabolite of a number of pyrethroids and thus lacks specificity to compounds that may have different potentials of reproductive toxicity. Another reason might be related to the fact that our subjects were university students who were not aware of their own fertility, whereas the previous study subjects were infertility patients. However, the multiple regression models could explain only a limited fraction of total variance in serum levels of hormones. Identification of other contributors is warranted.
FOXM1 mediates resistance to docetaxel in gastric cancer via up‐regulating Stathmin
Authors: Li Xiaoxiao , Yao Ruyong , Yue Lu , Qiu Wensheng , Qi Weiwei , Liu Shihai , Yao Yasai , Liang Jun
Published: March 2014

Docetaxel is commonly used as an effective chemotherapeutic drug for gastric cancer patients recently. With the increasing emergence of docetaxel resistance nowadays, identification of suitable biomarkers for predicting chemosensitivity to docetaxel may be a key role for improving therapeutic effects for gastric cancer patients. In this study, we investigated the correlation between the expression of transcription factor forkhead box protein M1 (FOXM1) and chemotherapy response to docetaxel in gastric cancer, the possible mechanism for which was further explored. As a result, FOXM1 overexpression was shown to mediate resistance to docetaxel in gastric cancers. It altered microtubule dynamics to protect tumour cells from docetaxel‐induced apoptosis. Mechanistic investigations revealed that tubulin‐destabilizing protein Stathmin, which mediated docetaxel resistance in FOXM1‐silenced gastric cancer cells, is a direct down‐stream target of FOXM1, whereas another microtubule dynamics protein mitotic centromere–associated kinesin (MCAK), shown to be related to docetaxel resistance in gastric cancer cells, is not associated with FOXM1 expression significantly. These results were further provided by immunohistochemical analysis, indicating that FOXM1 and Stathmin expression levels were correlated in 103 post‐operational gastric cancer specimens. Moreover, when we attenuated FOXM1 expression with FOXM1 inhibitor thiostrepton, docetaxel resistance in gastric cancers was found to be reversed, simultaneously with the down‐regulation of FOXM1 and Stathmin. Therefore, FOXM1 can be a useful marker for predicting and monitoring docetaxel response. Through the inhibition of FOXM1, docetaxel resistance can be reversed, and thus FOXM1 could be a new therapeutic target in docetaxel‐resistant gastric cancer.
Lack of β2‐adrenoceptors aggravates heart failure‐induced skeletal muscle myopathy in mice
Authors: Voltarelli Vanessa A. , Bechara Luiz R.G. , Bacurau Aline V.N. , Mattos Katt C. , Dourado Paulo M.M. , Bueno Carlos R. , Casarini Dulce E. , Negrao Carlos E. , Brum Patricia C.
Published: March 2014

Skeletal myopathy is a hallmark of heart failure (HF) and has been associated with a poor prognosis. HF and other chronic degenerative diseases share a common feature of a stressed system: sympathetic hyperactivity. Although beneficial acutely, chronic sympathetic hyperactivity is one of the main triggers of skeletal myopathy in HF. Considering that β2‐adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle, we presently evaluated the contribution of β2‐adrenoceptors for the morphofunctional alterations in skeletal muscle and also for exercise intolerance induced by HF. Male WT and β2‐adrenoceptor knockout mice on a FVB genetic background (β2KO) were submitted to myocardial infarction (MI) or SHAM surgery. Ninety days after MI both WT and β2KO mice presented to cardiac dysfunction and remodelling accompanied by significantly increased norepinephrine and epinephrine plasma levels, exercise intolerance, changes towards more glycolytic fibres and vascular rarefaction in plantaris muscle. However, β2KO MI mice displayed more pronounced exercise intolerance and skeletal myopathy when compared to WT MI mice. Skeletal muscle atrophy of infarcted β2KO mice was paralleled by reduced levels of phosphorylated Akt at Ser 473 while increased levels of proteins related with the ubiquitin‐–proteasome system, and increased 26S proteasome activity. Taken together, our results suggest that lack of β2‐adrenoceptors worsen and/or anticipate the skeletal myopathy observed in HF.
Inhibitory effects of hydrogen sulphide on pulmonary fibrosis in smoking rats via attenuation of oxidative stress and inflammation
Authors: Zhou Xiang , An Guoyin , Chen Jianchang
Published: March 2014

Accumulating evidence has demonstrated that hydrogen sulphide (H2S) is involved in the pathogenesis of various respiratory diseases. In the present study, we established a rat model of passive smoking and investigated whether or not H2S has protective effects against pulmonary fibrosis induced by chronic cigarette smoke exposure. Rat lung tissues were stained with haematoxylin‐eosin and Masson's trichrome. The expression of type I collagen was detected by immunohistochemistry. Oxidative stress was evaluated by detecting serum levels of malondialdehyde, superoxide dismutase and glutathione peroxidase and measuring reactive oxygen species generation in lung tissue. Inflammation was assessed by measuring serum levels of inflammatory cytokines, including high‐sensitivity C‐reactive protein, tumour necrosis factor‐α, interleukin (IL)‐1β and IL‐6. The protein expression of Nrf2, NF‐κB and phosphorylated mitogen‐activated protein kinases (MAPKs) in the pulmonary tissue was determined by Western blotting. Our findings indicated that administration of NaHS (a donor of H2S) could protect against pulmonary fibrosis in the smoking rats. H2S was found to induce the nuclear accumulation of Nrf2 in lung tissue and consequently up‐regulate the expression of antioxidant genes HO‐1 and Trx‐1 in the smoking rats. Moreover, H2S could also reduce cigarette smoking‐induced inflammation by inhibiting the phosphorylation of ERK 1/2, JNK and p38 MAPKs and negatively regulating NF‐κB activation. In conclusion, our study suggests that H2S has protective effects against pulmonary fibrosis in the smoking rats by attenuating oxidative stress and inflammation.
Advances in the cellular immunological pathogenesis of type 1 diabetes
Authors: Li Min , Song Lu‐Jun , Qin Xin‐Yu
Published: March 2014

Type 1 diabetes is an autoimmune disease caused by the immune‐mediated destruction of insulin‐producing pancreatic β cells. In recent years, the incidence of type 1 diabetes continues to increase. It is supposed that genetic, environmental and immune factors participate in the damage of pancreatic β cells. Both the immune regulation and the immune response are involved in the pathogenesis of type 1 diabetes, in which cellular immunity plays a significant role. For the infiltration of CD4+ and CD8+ T lymphocyte, B lymphocytes, natural killer cells, dendritic cells and other immune cells take part in the damage of pancreatic β cells, which ultimately lead to type 1 diabetes. This review outlines the cellular immunological mechanism of type 1 diabetes, with a particular emphasis to T lymphocyte and natural killer cells, and provides the effective immune therapy in T1D, which is approached at three stages. However, future studies will be directed at searching for an effective, safe and long‐lasting strategy to enhance the regulation of a diabetogenic immune system with limited toxicity and without global immunosuppression.
Gene profile in the spleen under massive partial hepatectomy using complementary DNA microarray and pathway analysis
Authors: Arakawa Yusuke , Shimada Mitsuo , Utsunomiya Tohru , Imura Satoru , Morine Yuji , Ikemoto Tetsuya , Mori Hiroki , Kanamoto Mami , Iwahashi Shuichi , Saito Yu , Takasu Chie
Published: March 2014

Background and Aim

In general, the spleen is one of the abdominal organs connected by the portal system, and a splenectomy improves hepatic functions in the settings of partial hepatectomy (Hx) for portal hypertensive cases or living donor liver transplantation with excessive portal vein flow. Those precise mechanisms remain still unclear; therefore, we investigated the DNA expression profile in the spleen after 90% Hx in rats using complementary DNA microarray and pathway analysis.

Methods

 Messenger RNAs (mRNAs) were prepared from three rat spleens at each time point (0, 3, and 6 h after 90% Hx). Using the gene chip, mRNA was hybridized to Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix®) and pathway analysis was done with Ingenuity Pathway Analysis (IPA®).

Results

We determined the 3‐h or 6‐h/0‐h ratio to assess the influence of Hx, and cut‐off values were set at more than 2.0‐fold or less than 1/2 (0.5)‐fold. Chemokine activity‐related genes including Cxcl1 (GRO1) and Cxcl2 (MIP‐2) related pathway were upregulated in the spleen. Also, immediate early response genes including early growth response‐1 (EGR1), FBJ murine osteosarcoma (FOS) and activating transcription factor 3 (ATF3) related pathway were upregulated in the spleen.

Conclusions

We concluded that in the spleen the expression of numerous inflammatory‐related genes would occur after 90% Hx. The spleen could take a harmful role and provide a negative impact during post Hx phase due to the induction of chemokine and transcription factors including GRO1 and EGR1.
Addition of mesalazine for subclinical post‐surgical endoscopic recurrence of Crohn's disease despite preventive thiopurine therapy: A case–control study
Authors: Zabana Yamile , Mañosa Míriam , Cabré Eduard , Bernal Isabel , Marín Laura , Lorenzo‐Zúñiga Vicente , Moreno Vicente , Boix Jaume , Domènech Eugeni
Published: March 2014

Background and Aim

Thiopurines prevent Crohn's disease (CD) endoscopic recurrence (ER) at least in 50% of patients 1 year after surgery. This study aimed to evaluate the value of adding mesalazine in patients with subclinical ER despite preventive thiopurine therapy.

Methods

Crohn's disease patients with ileocecal resection treated with thiopurines for postsurgical recurrence prevention in whom mesalazine was added (cases) to treat ER without clinical recurrence (CR) were identified and compared with those in whom no treatment was added to thiopurines (controls). All patients were followed up for at least 1 year from the index endoscopy. Development of CR as well as evolution of mucosal lesions was evaluated.

Results

Thirty‐seven patients were included (19 cases and 18 controls). Initial Rutgeerts' score was i2 in 16 patients (9 cases and 7 controls), and i3 in 21 patients (10 cases and 11 controls). After a median clinical follow‐up of 59 months (interquartile range 22–100) from the index endoscopy, six cases (32%) and two controls (11%) developed CR (P = 0.2). After a median time to last endoscopic follow‐up of 23 months (interquartile range 17–71), 18 patients (49%) showed improvement in Rutgeerts' score, 11 patients (30%) demonstrated progression of mucosal lesions, and 8 (22%) had no changes, with no differences between study groups.

Conclusions

The addition of mesalazine seems to be of no benefit in patients with subclinical endoscopic recurrence while on thiopurine prevention. Moderate endoscopic postsurgical recurrence while on thiopurines may even revert with no additional therapy in some patients.
Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction
Authors: Nakai Yousuke , Isayama Hiroyuki , Kawakubo Kazumichi , Kogure Hirofumi , Hamada Tsuyoshi , Togawa Osamu , Ito Yukiko , Matsubara Saburo , Arizumi Toshihiko , Yagioka Hiroshi , Takahara Naminatsu , Uchino Rie , Mizuno Suguru , Miyabayashi Koji , Yamamoto Keisuke , Sasaki Takashi , Yamamoto Natsuyo , Hirano Kenji , Tada Minoru , Koike Kazuhiko
Published: March 2014

Background and Aim

Tumor involvement to the orifice of cystic duct (OCD) is a risk factor for cholecystitis after self‐expandable metallic stent (SEMS) placement, but its prevention is still difficult. We conducted this multicenter analysis to clarify a type of SEMS or a method to place SEMS which would decrease the incidence of cholecystitis after SEMS placement.

Methods

The incidence of cholecystitis was studied in consecutive patients receiving SEMS for distal malignant biliary obstruction in five tertiary care centers. Multiple logistic regression analysis was performed to evaluate risk factors for cholecystitis.

Results

A total of 376 patients who received SEMS placement for distal malignant biliary obstruction were analyzed. Tumor involvement to OCD was diagnosed in 25.3%. Overall incidence of cholecystitis was 6.9%. Cholecystitis was observed in 8.0% of 300 patients with covered SEMS, 16.8% of 95 patients with tumor involvement to OCD, 10.8% of 234 patients with SEMS of high axial force (AF), and 12.0% of 158 patients with SEMS length ≤ 60 mm. In the multivariate analysis, tumor involvement to OCD (odds ratio [OR] 5.40, P < 0.001), SEMSs with high AF (OR 5.33, P = 0.002), and SEMS length ≤ 60 mm (OR 3.19, P = 0.010) are risk factors. Among patients with tumor involvement to OCD, the incidence of cholecystitis in SEMS with high and low AF was 25.0% and 5.0%, respectively.

Conclusion

This study with an expanded cohort reconfirmed tumor involvement to OCD as a risk factor for cholecystitis after SEMS placement. SEMS with low AF might decrease cholecystitis.
He Said What? Guided Cognitive Reframing About the Co‐Resident Father/Stepfather–Adolescent Relationship
Authors: Cookston Jeffrey T. , Olide Andres , Parke Ross D. , Fabricius William V. , Saenz Delia S. , Braver Sanford L.
Published: March 2014

We studied young adolescents' seeking out support to understand conflict with their co‐resident fathers/stepfathers, and the cognitive and affective implications of such support‐seeking, phenomena we call guided cognitive reframing. Our sample included 392 adolescents (Mage = 12.5, 52.3% female) who were either ofMexican orEuropean ancestry and lived with their biological mothers and either a stepfather or a biological father. More frequent reframing was associated with more adaptive cognitive explanations for father/stepfather behavior. Cognitions explained the link between seeking out and feelings about the father/stepfather and self. Feelings about the self were more strongly linked to depressive symptoms than cognitions. We discuss the implications for future research on social support, coping, guided cognitive reframing, and father–child relationships.
The dynamic lives of macrophage and dendritic cell subsets in atherosclerosis
Authors: Taghavie‐Moghadam Parésa L. , Butcher Matthew J. , Galkina Elena V.
Published: March 2014

Atherosclerosis, the major pathological process through which arterial plaques are formed, is a dynamic chronic inflammatory disease of large‐ and medium‐sized arteries in which the vasculature, lipid metabolism, and the immune system all play integral roles. Both the innate and adaptive immune systems are involved in the development and progression of atherosclerosis but myeloid cells represent the major component of the burgeoning atherosclerotic plaque. Various myeloid cells, including monocytes, macrophages (MΦs), and dendritic cells (DCs) can be found within the healthy and atherosclerotic arterial wall, where they can contribute to or regulate inflammation. However, the precise behaviors and functions of these cells in situ are still active areas of investigation that continue to yield exciting and surprising new data. Here, we review recent progress in understanding of the complex biology of MΦs and DCs, focusing particularly on the dynamic regulation of these subsets in the arterial wall and novel, emerging functions of these cells during atherogenesis.
QT and P‐wave dispersions in rheumatic heart disease: Prospective long‐term follow up
Authors: Alp Hayrullah , Baysal Tamer , Altın Hakan , Karataş Zehra , Karaarslan Sevim
Published: March 2014

Background

Simple electrocardiogram (ECG) markers have been used to evaluate conduction times. Acute rheumatic fever (ARF) is an autoimmune disease that affects these conduction times. The aim of this prospective long‐term follow‐up study was to evaluate QT, QTc and P‐wave dispersions in children with ARF and chronic rheumatic heart disease (CRHD).

Methods

Sixty‐four patients with ARF, 33 patients with CRHD and 41 healthy, age‐ and sex‐matched control subjects were included in the study. The ARF patients were divided into two subgroups: carditis and arthritis. Echocardiographic and ECG measurements at the onset of diagnosis and final evaluation were included.

Results

QT, QTc and P‐wave dispersions were significantly greater in both the ARF carditis and CRHD groups than the ARF arthritis and control subjects during the initial and final analysis (for all, P < 0.001). There was no significant statistical difference in QT, QTc and P‐wave dispersion between the initial and final analysis in each groups. Severity of mitral regurgitation and left atrial enlargement were found to be positively correlated with P‐wave dispersion (r = 0.438, P < 0.001; r = 0.127, P < 0.001, respectively). QT, QTc and P‐wave dispersion greater than 52, 60 and 57 ms, respectively, had higher sensitivity and specificity for predicting ARF carditis.

Conclusion

These ECG measurements can be used in the diagnosis of ARF carditis as minor criteria with modified Jones criteria. In contrast, this increase in the dispersions is permanent in patients with ARF carditis.
Sex‐specific reproductive components and pollination ecology in the subdioecious shrubFuchsia microphylla
Authors: Cuevas E. , Jiménez R. , Lopezaraiza‐Mikel M.
Published: March 2014

In subdioecious populations, functional female, male and hermaphrodite individuals coexist. Subdioecy may be a transitional state towards dioecy or a breakdown of dioecy, although lability in sex expression may maintain subdioecy as a stable condition. To better understand the ecological aspects involved in sex ratio dynamics and breeding system evolution, we studied the pollination and female fitness components of female and hermaphrodite individuals of the subdioecious shrubFuchsia microphylla. In two natural populations at the Trans‐Mexican Volcanic Belt we estimated female frequency and several reproductive components of female and hermaphrodite plants under natural pollination and experimental pollination treatments. Average female frequency was 42%, and on average, 42.5% of hermaphrodites produced fruits. Female plants showed a 17‐fold female fertility advantage over hermaphrodites through increased fruit production, as the number of seeds and germination rates did not differ between morphs. Hermaphrodite flowers were larger, with similar nectar production and concentration to female flowers, and pollinators did not show consistent morph preferences. Some hermaphrodites produced fruits autonomously, and female flowers excluded from pollinators produced fruits putatively by apomixis. Fruit production in hermaphrodites, but not in females, was related to height, suggesting increased investment of hermaphrodites in the female function at higher resource status. For sex ratios to be at equilibrium, the female fertility advantage should be reduced about eightfold. However, it may be that hermaphrodites are maintained by producing fruits at no cost to the male function at higher resource status, as the gender plasticity hypothesis proposes.
Classroom Climate and Political Learning: Findings from a Swedish Panel Study and Comparative Data
Authors: Persson Mikael
Published: March 2014

Numerous studies have shown that an open classroom climate for discussion increases students' civic knowledge. However, most previous studies draw on cross‐sectional data and have not been able to show that the effect is causal. This article presents results from a Swedish panel survey following students during the first year in the gymnasium (upper secondary level). Using this study, we are better equipped to evaluate the link between an open classroom climate and political knowledge. Results suggest that the effect is causal. A 10% increase in open classroom climate is associated with about 5 percentage points higher knowledge. The beneficial effect of an open classroom climate is an important insight that should be seriously considered not only by researchers but also by educational policy makers, school managements, and teachers.
“We Must Be the Change We Want to See in the World”: Integrating Norms and Identities through Social Interaction
Authors: Smith Laura G. E. , Thomas Emma F. , McGarty Craig
Published: March 2014

In this article, we propose a social psychological mechanism for the formation of new social change movements. Here, we argue that social change follows the emergence of shared injunctive social norms that define new collective identities, and we systematically spell out the nature of the processes through which this comes about. We propose that these norms and identities are created and negotiated through validating communication about a normative conflict; resulting in an identity‐norm nexus (INN), whereby people become the change they want to see in the world. We suggest that injunctive norms are routinely negotiated, validated, and integrated with shared identity in order to create the potential to effect change in the world. Norms and identities need not be integrated or connected in this way, but the power of social actors to form new social movements to bring about sociopolitical change will tend to be severely limited unless they can bring about the integration of identity and action.