bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous hybrid peripheral re-vascularization: early results
Authors: Yurekli Ismail , Gokalp Orhan , Gunes Tevfik , Yilik Levent , Gurbuz Ali
Published: September 2013

Endovascular and open surgical interventions may be combined in treatment of peripheral arterial disease. In this study, we presented our simultaneous hybrid peripheral interventions under the light of current literature data. Eleven patients who were operated for occlusive peripheral arterial disease without aneurysms between June 2008 and November 2010 at our hybrid operating room were investigated retrospectively. Generally, endovascular intervention was performed initially, and then followed by surgery. After hybrid interventions, control angiograms were held during the same session. None of the patients experienced either stent or graft occlusion during early postoperative period. Primary patency rate was found to be 100% for the postoperative first six months. Ankle-brachial indices (ABI) increased significantly during postoperative period and clinical symptoms were relieved in all patients (mean preoperative ABI: 0.43 ± 0.08, mean postoperative sixth month ABI: 0.87 ± 0.08). Peripheral hybrid interventions may be performed both in separate sessions and also simultaneously by experienced teams if an angiography device is available within the operating room.
Carotid endarterectomy in the elderly: risk factors, intraoperative carotid hemodynamics and short-term complications: a UK tertiary center retrospective analysis
Authors: Sadideen H , Thomson D R , Lewis R R , Padayachee T S , Taylor P R
Published: September 2013

This retrospective analysis aims to demonstrate the safety of carotid endarterectomy (CE) in patients >75 years with particular attention paid to intraoperative hemodynamics. Four hundred and ninety-six consecutive patients with >70% symptomatic and asymptomatic stenosis who underwent CE were prospectively assessed and divided into those <75 years ( n = 408; mean 64 years) and those >75 years ( n = 88; mean 78 years). Associated risk factors, hemodynamic parameters, surgical techniques and 30-day perioperative complications were compared. Carotid artery stump pressures of <25 mmHg (13 versus 29%) and middle cerebral artery velocities of <20 cm/sec (46 versus 29%) were more common in those >75 years ( P = 0.0001 and P <0.005, respectively). However, there was no difference in the frequency of intraluminal shunt (34% in both groups) or synthetic patch usage (primary patching: 12.5%, older group versus 11%, younger group; secondary patching: 34% in both groups), and no difference in the combined 30-day stroke and death rates (3.4%, >75 years versus 1.1%, <75 years; P = 0.425). CE in this cohort of patients >75 years was not associated with increased morbidity or mortality. Altered intraoperative hemodynamics were not associated with increased use of shunting or patching. This analysis supports CE as a safe procedure in the elderly.
Comparison of β-aminopropionitrile-induced aortic dissection model in rats by different administration and dosage
Authors: Li Jia-si , Li Hai-yan , Wang Liang , Zhang Lei , Jing Zai-ping
Published: September 2013

This study compared three β-aminopropionitrile (BAPN) treatment rats to find the optimal BAPN model for thoracic aortic dissection and aneurysm in one study. Sixty rats were divided into five groups: control, injected control, 0.25% and 0.4% BAPN treatment (orally), and 667 mg/kg/day BAPN injection subcutaneously. Incidence of aortic dissection and aneurysm, aortic weight and diameter were measured directly. Thickness of media and area of aorta were measured by hematoxylin and eosin and Victoria blue staining. The mortality, incidence of aortic dissection and the rupture rate of dissected aneurysm in 0.25% group was much higher than in the other two BAPN treatment groups. The diameter of thoracic aorta in 0.25% and the whole aorta in 0.4% group significantly increased. Media thickness and area of thoracic aorta were increased by 91% and 54% in 0.25% group, and by 17% and 12% in the BAPN injection group. Thickness and area were increased by 49% and 35% on thoracic aorta, and 29% and 46% on abdominal aorta in 0.4% group. In conclusion, 0.25%, 0.4% and BAPN injection groups might be appropriate for aortic dissection and pharmaceutical study, thoracic-abdominal aortic aneurysm or dilation and biomechanical research, respectively.
Successful endovascular management of giant splenic artery aneurysms
Authors: Ho M F , Chan Y C , Cheng S W
Published: September 2013

Giant pseudoaneurysms of the splenic artery, with a diameter of 5 cm or more, are rare surgical emergencies, and conventional open surgery usually involves splenectomy. The aim of this study is to report two cases from our institution and to review the world's literature on successful endovascular treatment of patients with giant splenic artery pseudoaneurysms. A retrospective review of a prospectively entered departmental computerized database was performed for the two patients from our institution. Articles were searched electronically from PubMed and Medline, using the terms ‘giant splenic artery’, ‘endovascular’ and ‘embolization’; and relevant cases were reviewed from the world's literature. We hereby report two patients with giant splenic artery pseudoaneurysms who were treated successfully with endovascular procedures. In addition to the two patients from our institution, there were five patients with giant splenic artery pseudoaneurysms in the published literature who underwent successful endovascular management. The first patient of our series had the largest pseudoaneursym size of 7.2 × 8.1 cm, which is the largest documented pseudoaneursym in the current literature. We report two cases of giant splenic artery pseudoaneurysm with one being the largest pseudoaneurysm treated with endovascular technique in the current literature. Endovascular coil embolization of main trunk of splenic artery is less invasive than open surgical treatment for giant splenic artery pseudoaneurysm, and circumvents the problem of difficult exposure, especially in those patients with significant co-morbidity.
Aorto-iliac aneurysm infected by Brucella: distinctive presentation patterns of a rare entity
Authors: Kakkos S K , Papadoulas S , Lampropoulos G , Marangos M , Kalogeropoulou C , Tsolakis I A
Published: September 2013

There is currently a lack of information on presentation patterns and the appropriate investigation and treatment of aortic brucellosis. Herein a case affecting the iliac component of an aorto-iliac aneurysm, managed successfully with in situ graft repair, is reported. A review of the literature identified 25 cases, with the infrarenal abdominal aorta (65%) followed by the ascending thoracic aorta (23%) being mostly affected; only our case involved the iliacs. Aortic brucellosis affected mostly older men, caused pain more often than fever (in 73% and 57%, respectively), and involved frequently the spine or the aortic valve ( n = 14, 56%). Preoperative diagnosis was made more often in the presence of fever (67% versus 18% in afebrile patients, P = 0.021). In situ aneurysm repair in the form of open (54%) or endovascular (8%) grafting was mostly performed. Mortality was 12% and graft infection was 13% at two years. In conclusion, aortic brucellosis has unique presentation patterns, usually affecting an abnormal or aneurysmal aorta and/or due to a contiguous spinal or aortic valve infection. Acute symptomatology with pain and/or fever occurs very often and should raise suspicion for aortic infection. Despite the seriousness of aortic involvement, mortality and reinfection rates are within acceptable levels.
Constructing a leader’s identity through a leadership development programme
Authors: Moorosi Pontso
Published: September 2013

This article explores the notion of leadership identity construction as it happens through a leadership development programme. Influenced by a conception that leadership development is essentially about facilitating an identity transition, it uses an intersectional approach to explore school leaders’ identity construction as it was shaped and influenced by experiences on the leadership development programme. The article draws data from a mixed-methods study that evaluated the impact of the leadership training programme offered to practising school leaders in South Africa. In order to examine the process of leadership identity construction, the article draws from data where identity work was visible. It argues that categories of identity – gender, race and social class – interacted simultaneously with the contexts and backgrounds of participants to shape and influence the outcome of the leadership development programme. This complex intersection enabled unexpected outcomes where women appeared to benefit more from the programme despite their less privileged entry status. The article calls for more work that asks direct questions on leaders’ construction of identity in order to inform leadership development programmes more meaningfully.
Pedagogical leadership in the 21st century
Authors: Male Trevor , Palaiologou Ioanna
Published: September 2013

Literature examining effective leadership in education describe a number of models such as Transformational, Learner-Centred, Distributed and Situational. A similar example is ‘pedagogical leadership’, a phrase that frequently appears in literature and one referring to forms of practice that shape and form teaching and learning to be integrated in leadership. In this paper, however, we will argue that the term pedagogy is an ambiguous one when it is attached to the concept of leadership and requires further explanation, particularly in the 21st century. Our conclusions are informed by findings from research undertaken by us with headteachers and leaders of early years settings in England during 2012. One of the key findings is that we should shift from using models of leadership and instead to view leadership as a praxis that is not merely concerned with the dichotomy of teaching, learning and outcomes, but is also concerned with an integrated conceptualisation of the relations between teaching, the learning ecology of the community and the social set of axes in which the educational organisation is set. This understanding of pedagogical leadership is thus concerned with the links between desired educational outcomes and the set of social realities that surround the educational setting.
Exploring ethical dilemmas for principals arising from role conflict with school counsellors
Authors: Kimber Megan , Campbell Marilyn
Published: September 2013

Acting in the best interests of students is central to the moral and ethical work of schools. Yet tensions can arise between principals and school counsellors as they work from at times opposing professional paradigms. In this article we report on principals’ and counsellors’ responses to scenarios covering confidentiality and the law, student/teacher relationships, student welfare and psychological testing of students. This discussion takes place against an examination of ethics, ethical dilemmas and professional codes of ethics. While there were a number of commonalities among principals and school counsellors that arose from their common belief in education as a moral venture, there were also some key differences among them. These differences centred on the principals’ focus on the school as a whole and counsellors’ focus on the welfare of the individual student. A series of recommendations is offered to assist principals to navigate ethical dilemmas such as those considered in this article.
Emotion in leadership
Authors: Yamamoto Julie K. , Gardiner Mary E. , Tenuto Penny L.
Published: September 2013

This article contributes to an emergent literature of empirical studies on how emotion impacts leadership. The purpose of the study was to examine how secondary school administrators derived meaning from critical incidents of significant emotional events retrospectively, and how the understanding impacted leadership. A conceptual framework of emotion as a critical element of leadership, and emotion as an element of authentic leadership, was used for sensitivity in examining and analyzing the data from a multi-case study with nine practicing USA secondary school administrators. Four themes relating to emotion in leadership were found, and a model was conceptualized. The article concludes with recommendations for further research.
Resolving equipment failure causes by root cause analysis and theory of inventive problem solving
Authors: Viveros Pablo , Zio Enrico , Nikulin Christopher , Stegmaier Raúl , Bravo Gloria
Published: September 2013

Failure causes of production systems need to be readily identified, for effective recovery solutions. Root cause analysis can be used for this, integrated by a method for identifying coherent and sustainable solutions. In this article, root cause analysis for failure cause identification is coupled with a method of problem solving to guide the search for effective solutions, called theory of inventive problem solving. The integration of these methodologies is implemented and demonstrated on a real case concerning the solution to the potential failure of the equipment used in the torque test performed on truck engines used in high-tonnage mining operation. The incorporation of a key performance indicator analysis allows evaluating realistically the results obtained and determining the success of the solution.
A methodology for the investigation of the reliability and safety of unique technical systems
Authors: Berman Aleksandr F , Nikolaychuk Olga A , Yurin Aleksandr Y , Pavlov Aleksandr I
Published: September 2013

A methodology for the modelling and investigation of the safety of complex technical systems is proposed. Complex technical systems are considered to be unique technogenic objects that are designed in one or two instances, implementing extreme technologies, and are subjected to the influence of mechanical, physical and chemical factors. The generalised cause–effect complex and the scenario of violation of the reliability and safety for such systems are formulated. Dynamic models related to the formation of the system states are delineated – from an initial defectiveness of the construction to the damages, destruction, failure, pre-emergency, emergency and possible technogenic catastrophe. A concept of an intelligent program system, which is intended for the computer-aided investigation of reliability and safety, is described. The example for the application of the proposed methodology describes the safety violation of a pipeline under an ammonia synthesis column. The results obtained provide for the efficient and qualitative investigation of revealing hazards and for the delineation of techniques and aids to ensure reliability and safety.
On the profust reliabilities of consecutive k-out-of-n systems
Authors: Demir Atalay Sevcan , Mert Ali , Gultekin Ozge E
Published: September 2013

System reliability concept is a very popular topic among scientific research areas. Systems may be classified based on their structures such as linear and circular, based on their evaluation characteristics such as fuzzy and nonfuzzy states and based on working principles such as F and G systems. Linear and circular system distinction is originated from ordering difference of components. System and/or component states can be evaluated as fuzzy and nonfuzzy. If system and component states are both evaluated as nonfuzzy, then the reliability of such a system is considered as conventional reliability. On the contrary, if system or component states are evaluated as fuzzy, then reliability of such a system is considered as fuzzy reliability. While the working principle is defined with respect to the number of failed components for an F system, it is defined with respect to the number of working components for a G system. A consecutive k-out-of- n:F system composes of a sequence of n ordered components such that the system is failed if and only if at least k consecutive components in the system are failed. Similarly, consecutive k-out-of- n:G system composes of a sequence of n ordered components such that the system works if and only if at least k consecutive components in the system work. In this study, we research the profust (states of components are evaluated as nonfuzzy and state of system is evaluated as fuzzy) reliabilities of consecutive k-out-of- n:F and G systems considering both linear and circular sequence of n components. The reliabilities of these systems are evaluated for independent and identically distributed components. Easy-to-use formulas for the reliabilities of these systems are obtained using the distribution of some run statistics. In order to use these formulas, the working probability of a component at any time is sufficient. Some numerical results and figures are also presented to acquire some information about the reliabilities of related systems and to compare performance differences between conventional and profust reliabilities of systems considered in this study.
Comparing topological and reliability-based vulnerability analysis of Iran power transmission network
Authors: Alipour Zohre , Monfared Mohammad Ali Saniee , Zio Enrico
Published: September 2013

Power grids are one of the most important and critical infrastructures which societies rely upon for well-being. Their topological (structural) characteristics related to vulnerability can be analyzed from the viewpoint of complex network theory. In this article, we incorporate into this viewpoint some relevant reliability properties and apply the analysis framework to study the high-voltage power grid in Iran. To identify weak points in the structure, we look at four different centrality measures, namely, degree, betweenness, information and closeness, and analyze their correlation properties. This allows providing a more comprehensive picture of the vulnerability characteristics of the power grid structure. By our analysis, we show that reliability-based characteristics are different from purely topological ones as they are mostly uncorrelated. We also use a voting aggregation method, the Borda Count method, to perform an overall ranking of the most vulnerable nodes, considering both intentional attacks and random failures.
Remembering arrivals of refugees by boat in a Canadian context
Authors: Mannik Lynda
Published: September 2013

On 12 July 1987, 174 people traveled from Rotterdam to Charlesville, Nova Scotia, on the Amelie in search of asylum. In Canadian national newspapers, their arrival was immediately turned into a crisis of securitization, which is common practice for such events. Conversely, local reports portrayed this event as a critical moment when regional Canadian identity was performed through commonly understood and commonly practiced all-inclusive hospitality. This article will look at how collective memories were produced and circulated on various levels in press reports, with a focus on the way local memories and local press reports supported international views of ideal Canadian humanitarianism and hospitality.
Time-based calibrations of pressure sensors improve the estimation of force signals containing impulsive events
Authors: Cazzola Dario , Trewartha Grant , Preatoni Ezio
Published: September 2013

Piezoresistive pressure sensors are widely used in biomechanics applications involving both static and dynamic loading conditions. The overall accuracy of these sensors has been reported previously in the literature, and multiple linear or polynomial custom calibrations have been proposed to enhance sensors’ performance mainly in low dynamics conditions. The aim of this technical note was to propose a ‘point-to-point’ time-based method to improve Tekscan F-Scan sensor calibration procedures in reconstructing a force signal with variable dynamic content and duration, using an application-specific loading pattern, characterised by an initial impact followed by a slow dynamic phase. The performance of the proposed calibration procedure was compared with four methods divided into time-based calibrations (‘point-to-point’, ‘log time–based’ and Tekscan ‘step’) and linear calibrations (‘drop-ball’ and Tekscan ‘single-point’). The ‘point-to-point’ calibration was the only method providing accurate force estimation over the entire duration, showing an inaccuracy of about 10% both in impact and slow dynamic phases. Tekscan default calibrations (‘step’ and ‘single-point’) underestimated the criterion force by ~60% over the impact phase but performed better in the slow dynamic phase (~20% of inaccuracy). ‘Log time–based’ and ‘drop-ball’ performed well during the impact phase (~11%) but overestimated the slow dynamic phase by ~170%. For this reason, we recommend ‘point-to-point’ calibration for estimation of forces which are characterised by an initial impulsive event and a subsequent slow-changing load. These findings highlight the importance of selecting the most appropriate calibration with respect to signal dynamics, in terms of loading range, loading pattern and impact duration.
Teacher Interrupted
Authors: Mulholland Rosie , McKinlay Andy , Sproule John
Published: September 2013

A sample of 399 secondary school teachers (156 males, 243 females, 18 schools) responded to a survey questionnaire containing one measure of stress and two measures of strain. The Stressors in Teaching Scale (SITS), developed specifically to place work stress within the Scottish “teaching” context (Mulholland, 2005), gauged work stress. The General Health Questionnaire-30 (GHQ-30; Goldberg, 1972) and Glasgow Symptom Checklist (GSC; Mahmood, 1999) presented a unique opportunity to compare teachers’ perception of strain with a “general” and “clinical” population. Positive correlations were observed between work stress and strain. Perceptions of work stress and strain differed significantly according to teaching role. Quantitative job demands (e.g., “workload”) was the main predictor of strain, and middle managers, who held leadership and classroom teaching responsibilities, reported this feature of work and “changing demands” specifically, as significantly more stressful than senior managers. Middle managers’ experiences of work were reflective of a “pile-up” of stressors, indicative of quantitative and qualitative overload. Crucially, 22% of middle managers recorded strain scores (GHQ-30 case) indicative of psychiatric morbidity, and approximately 67% had experienced feelings of “personal ineffectiveness” and “depression” (GSC), normally associated with a “clinical” population. The unique interaction of “stressors” associated with teacher role, job demands, and job resources highlighted a range of risk factors (e.g., “workload,” “teaching-learning interface,” “professional ethos,” “change,” and “role”) that have the potential to affect health in the long term.
Island Lives
Authors: Heinz Matthew , MacFarlane Devon
Published: September 2013

In 2010-2011, the Vancouver Island Transgender Needs Assessment, a community-based, applied research project, sought to identify the health and social needs of trans people on Vancouver Island, British Columbia, Canada. An advisory board consisting of trans-identified community members and trans-service providers guided this descriptive analysis. A total of 54 individuals identifying as transgender participated in a survey modeled after the TransPULSE Ontario instrument. Of the participants, 43% identified on the transmasculine spectrum, 39% on the transfeminine spectrum, and 18% as transgender/genderqueer only. Participants were surveyed in regard to education, employment, and income; housing; health care needs and services; suicidality; violence; life satisfaction and attitudes toward self; posttransition experiences; and community belonging. They reported health care, social support, and public education/acceptance as top needs. The article concludes with a specific needs profile and a community-generated set of recommendations stressing the need for an island-based information and resourcing center.
Training of Library Assistants in Academic Library
Authors: Bamidele Itunu A. , Omeluzor Saturday U. , Imam Abayomi , Amadi Hannah U.
Published: September 2013

The purpose of this research is to identify the need to train and retrain library assistants in academic libraries. The researchers however used Babcock University Library to ascertain the impacts of training of library assistants. A descriptive design was adopted for this study. A total enumeration sampling method was used. The instrument used for data collection was a structured questionnaire. The population was made up of 30 respondents who were library assistants at the Babcock University Library, Nigeria. A total number of 30 questionnaires were administered. All the questionnaires were retrieved and were found useful giving a return rate of 100% used for this study. The result shows that library assistants were not given training in the area of system management and web searching. In addition, 27 (90%) of the respondents agreed that training will enhance their job performance while 30 (100%) of the respondents agreed that training will improve their skills to support library users in searching for information electronically. Based on the findings the researchers recommend that library assistants should be trained on electronic information technology usage as this will impact the overall service delivery in meeting the goals of the academic library.
A Comparison of State Assessment Scores Between Music and Nonmusic Students
Authors: Thornton Linda
Published: September 2013

For several years, an emphasis on standardized testing in certain subjects has often resulted in competition for student time and scheduling choices that may not favor music classes. However, a great deal of literature exists to indicate that music students achieve more success than nonmusic students on a variety of academic measures. The purpose of this study was to conduct a statewide comparison of test scores for students involved in voluntary music classes or ensembles and students not involved in such activities. Scores from almost 7,000 students in the three grades tested by the state (5, 8, 11) were generated from a variety of districts throughout the state. Significantly higher scores were found for students involved in music compared with students not involved in music. It would seem music students did not have a disadvantage on the state test, despite the time they spent on musical activities.
The Relation of Culture and Musical Play
Authors: Soccio Alison
Published: September 2013

Children express the cultures they bring into the classrooms through musical play. When children are left to their own devices they dance, create songs, and play instruments. Campbell emphasizes how children are immersed in musical activity throughout the entirety of their day; they use music for self-expression, to interact with others, and to entertain themselves. This literature review explores the relationship that exists between culture and musical play within the child, the family, and the school. These varying cultures have an impact on a child’s music education; a bridge must exist between each and this is often accomplished through play, a time during which children are left to freely explore their world on their own. As music educators, we must take the time to listen to and observe this musical play in our classrooms if we wish to encourage children to bring what they have learned from their family culture to their school culture.
Boys’ Perceptions of Singing
Authors: Warzecha Megan
Published: September 2013

Boys seem to progress through phases in which they like to sing in early elementary school, they think that singing is for girls and, thus, unacceptable in late elementary school, and then, gradually, singing again becomes acceptable later in life. Studies speak to the difficulty that choir directors have in recruiting boys. Research shows that this may be because of the perception of singing as being feminine gendered. Many studies investigate this perception in older males, but few have investigated it in younger boys. This literature review explores the various reasons why males of all ages describe a negative perception of singing, focusing on younger boys. Suggestions for possible solutions are offered for practicing teachers in the field of vocal music.
Perceptions of Early-career School Music Teachers Regarding Their Preservice Preparation
Authors: Legette Roy M.
Published: September 2013

The purpose of the present study was to examine the perceptions of early-career music teachers regarding their preservice music education program, with respect to its success in developing competencies needed to be effective in school music classrooms. An online survey was completed by 101 school music teachers designed to elicit responses related to the following questions: (a) What are early-career music teachers’ perceptions of their preparation for teaching in school music classrooms? (b) What aspects of their work do early-career music teachers find most challenging and rewarding? (c) What aspects of their preservice training do early-career music teachers perceive as most important for successful teaching in the early years of their careers? Most teachers expressed a need for more hands-on experiences, more discussion of pedagogical problems in a variety of settings, and classroom management. Implications for teaching and research are discussed.
The Effects of Limited, Restricted Music Practice on Overnight Memory Enhancement
Authors: Allen Sarah E. , Duke Robert A.
Published: September 2013

During evening practice sessions, 32 nonpianist musicians learned a short melody on piano, and then either learned a second short piano melody, learned a difficult unfamiliar piece on their principal instruments, practiced familiar material on their principal instruments, or engaged in no other music-related motor behavior prior to sleep; practice on the target melody was limited in terms of time and number of repetitions. All participants returned the next morning and were tested on their performance of the target piano melody. Previous research has revealed overnight enhancement of skills as a result of sleep. In the current study, however, our participants showed significant decrements in performance between evening training and morning test, though the extent of the decrements varied. We speculate that the lack of overnight improvements may have resulted from our regulating participants’ practice of the target melody during the training sessions and that strict, limited practice protocols may interfere with consolidation-based memory enhancement.
Blood spotlight on leukocytes and obesity
Authors: Carvalheira Jose Barreto Campello , Qiu Yifu , Chawla Ajay
Published: September 2013

The rise of obesity and its attendant pathological sequelae, including type 2 diabetes and coronary artery disease, constitute an ongoing public health catastrophe in both the developed and, more recently, the developing world. Although the underlying pathophysiology is complex, chronic low-grade inflammation has emerged as a central driver of both primary metabolic dysfunction and subsequent tissue failure. Importantly, this inflammation has been shown to arise as a consequence of both the disruption of homeostatic tissue resident leukocytes and the recruitment of antagonistic effector cells from the circulation. In this review, we discuss the roles of visceral adipose tissue’s salient leukocyte lineages in the transition to obesity and highlight key points at which this emerging immune axis may be manipulated for therapeutic effect.
Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions
Authors: Ohama Takashi , Wang Lifu , Griner Erin M , Brautigan David L
Published: September 2013

Background

Epithelial tissues depend on intercellular homodimerization of E-cadherin and loss of E-cadherin is central to the epithelial to mesenchymal transition seen in multiple human diseases. Signaling pathways regulate E-cadherin function and cellular distribution via phosphorylation of the cytoplasmic region by kinases such as casein kinases but the protein phosphatases involved have not been identified.

Results

This study shows protein Ser/Thr phosphatase-6 catalytic subunit (PP6c) is expressed in epithelial tissue and its mRNA and protein are robustly up-regulated in epithelial cell lines at high vs. low density. PP6c accumulates at adherens junctions, not tight junctions, co-immunoprecipitates with E-cadherin-catenin complexes without a canonical SAPS subunit, and associates directly with the E-cadherin cytoplasmic tail. Inducible shRNA knockdown of PP6c dispersed E-cadherin from the cell surface and this response was reversed by chemical inhibition of casein kinase-1 and prevented by alanine substitution of Ser846 in murine E-cadherin.

Conclusions

PP6c associates with E-cadherin in adherens junctions and is required to oppose casein kinase-1 to maintain cell surface localization of E-cadherin. There is feedback signaling to enhance PP6c transcription and boost protein levels in high density epithelial cells.
The prognostic value of Her4 receptor isoform expression in triple-negative and Her2 positive breast cancer patients
Authors: Machleidt Anna , Buchholz Stefan , Diermeier-Daucher Simone , Zeman Florian , Ortmann Olaf , Brockhoff Gero
Published: September 2013

Background

Not only four but rather seven differenthumanepidermal growth factor receptorrelated (Her) receptor tyrosine kinases (RTKs) have been described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified. A differential expression of Her4 isoforms does not, however, play any role in either the molecular diagnostics or treatment decision for breast cancer patients. The prognostic and predictive impact of Her4 expression in breast cancer is basically unclear.

Methods

We quantified the Her4 variants JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, and JM-b/CYT2 by isoform-specific polymerase chain reaction (qPCR) in (i) triple-negative, (ii) Her2 positive breast cancer tissues and (iii) in benign breast tissues.

Results

In all three tissue collectives we never found the JM-b/CYT1 or the JM-b/CYT2 isoform expressed. In contrast, the two JM-a/CYT1 and JM-a/CYT2 isoforms were always simultaneously expressed but at different ratios. We identified a positive prognostic impact on overall survival (OS) in triple-negative and event-free survival (EFS) in Her2 positive patients. This finding is independent of the absolute JM-a/CYT1 to JM-a/CYT2 expression ratio. In Her2 positive patients, Her4 expression only has a favorable effect in estrogen-receptor (ER)-positive but not in ER-negative individuals.

Conclusion

In summary, JM-a/CYT1 and JM-a/CYT2 but not JM-b isoforms of the Her4 receptor are simultaneously expressed in both triple-negative and Her2 positive breast cancer tissues. Although different expression ratios of the two JM-a isoforms did not reveal any additional information, Her4 expression basically indicates a prolonged EFS and OFS. An extended expression analysis that takes all Her receptor homologs, including the Her4 isoforms, into account might render more precisely the molecular diagnostics required for the development of optimized targeted therapies.
Gastric outlet obstruction at Bugando Medical Centre in Northwestern Tanzania: a prospective review of 184 cases
Authors: Jaka Hyasinta , Mchembe Mabula D , Rambau Peter F , Chalya Phillipo L
Published: September 2013

Background

Gastric outlet obstruction poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. There is a paucity of published data on this subject in our setting. This study was undertaken to highlight the etiological spectrum and treatment outcome of gastric outlet obstruction in our setting and to identify prognostic factors for morbidity and mortality.

Methods

This was a descriptive prospective study which was conducted at Bugando Medical Centre between March 2009 and February 2013. All patients with a clinical diagnosis of gastric outlet obstruction were, after informed consent for the study, consecutively enrolled into the study. Statistical data analysis was done using SPSS computer software version 17.0.

Results

A total of 184 patients were studied. More than two-third of patients were males. Patients with malignant gastric outlet obstruction were older than those of benign type. This difference was statistically significant (p < 0.001). Gastric cancer was the commonest malignant cause of gastric outlet obstruction where as peptic ulcer disease was the commonest benign cause. In children, the commonest cause of gastric outlet obstruction was congenital pyloric stenosis (13.0%). Non-bilious vomiting (100%) and weight loss (93.5%) were the most frequent symptoms. Eighteen (9.8%) patients were HIV positive with the median CD 4+ count of 282 cells/μl. A total of 168 (91.3%) patients underwent surgery. Of these, gastro-jejunostomy (61.9%) was the most common surgical procedure performed. The complication rate was 32.1 % mainly surgical site infections (38.2%). The median hospital stay and mortality rate were 14 days and 18.5% respectively. The presence of postoperative complication was the main predictor of hospital stay (p = 0.002), whereas the age > 60 years, co-existing medical illness, malignant cause, HIV positivity, low CD 4 count (<200 cells/μl), high ASA class and presence of surgical site infection significantly predicted mortality ( p< 0.001). The follow up of patients was generally poor as more than 60% of patients were lost to follow up.

Conclusion

Gastric outlet obstruction in our setting is more prevalent in males and the cause is mostly malignant. The majority of patients present late with poor general condition. Early recognition of the diagnosis, aggressive resuscitation and early institution of surgical management is of paramount importance if morbidity and mortality associated with gastric outlet obstruction are to be avoided.
Decreased fructose-1,6-bisphosphatase-2 expression promotes glycolysis and growth in gastric cancer cells
Authors: Li He , Wang Juan , Xu Huiyu , Xing Rui , Pan Yuanming , Li Wenmei , Cui Jiantao , Zhang Hongbing , Lu Youyong
Published: September 2013

Background

Increasing evidence suggests that cancer is a metabolic disease. Here, we investigated the potential role of fructose-1,6-bisphosphatase-2 (FBP2), the enzyme that catalyses the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate in glucose metabolism, in gastric cancer (GC) development.

Results

Our data indicated that FBP2 was downregulated in GC tissues (86.2%, 100/116), and absent or low FBP2 expression in GC tissues was correlated with poor survival of GC patients (P = 0.019). Conversely, ectopic expression of FBP2 in GC cells activated AMP-activated protein kinase (AMPK) signalling, inhibited the Akt-mTOR pathway, suppressed glucose metabolism, enhanced apoptosis, and reduced cell proliferation. Bisulphite genomic sequencing (BGS) in gastric cancer cell lines revealed that the FBP2 promoter region was densely methylated, and treatment of GC cells with the demethylation reagent, 5-aza-2-deoxycytidine (5-Aza), led to an increase in FBP2 expression. Importantly, forced expression of FBP2 abrogated tumour formation of these GC cells in nude mice.

Conclusion

Our results indicate that FBP2 does negatively regulate cell growth, and reduced expression of FBP2 may contribute to carcinogenesis for GC. These findings suggest that restoration of FBP2 expression can be a promising strategy for the target therapy of GC.
Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice
Authors: Zhang Zhen-Zhou , Shang Qian-Hui , Jin Hai-Yan , Song Bei , Oudit Gavin Y , Lu Lin , Zhou Tong , Xu Ying-Le , Gao Ping-Jin , Zhu Ding-Liang , Penninger Josef M , Zhong Jiu-Chang
Published: September 2013

Background

Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase which metabolizes angiotensin II (Ang II) to generate Ang-(1–7), has been shown to prevent cardiac hypertrophy and injury but the mechanism remains elusive. Irbesartan has the dual actions of angiotensin receptor blockade and peroxisome proliferator-activated receptor-γ (PPARγ) activation. We hypothesized that irbesartan would exert its protective effects on ACE2 deficiency-mediated myocardial fibrosis and cardiac injury via the PPARγ signaling.

Methods

10-week-old ACE2 knockout (ACE2KO; Ace2-/y) mice received daily with irbesartan (50 mg/kg) or saline for 2 weeks. The wild-type mice (Ace2+/y) were used to the normal controls. We examined changes in myocardial ultrastructure, fibrosis-related genes and pathological signaling by real-time PCR gene array, Western blotting, Masson trichrome staining and transmission electron microscope analyses, respectively.

Results

Compared with the Ace2+/y mice, cardiac expression of PPARα and PPARγ were reduced in Ace2-/y mice and the myocardial collagen volume fraction (CVF) and expression of fibrosis-related genes were increased, including transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), collagen I and collagen III. Moreover, ACE2 deficiency triggered cardiac hypertrophy, increased myocardial fibrosis and adverse ultrastructure injury in ACE2KO hearts with higher levels of atrial natriuretic factor (ANF) and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), without affecting cardiac systolic function. Intriguingly, treatment with irbesartan significantly reversed ACE2 deficiency-mediated pathological hypertrophy and myocardial fibrosis in Ace2-/y mice linked with enhancement of plasma Ang-(1–7) level and downregulation of AT1 receptor in heart. Consistent with attenuation of myocardial fibrosis and ultrastructure injury, the myocardial CVF and levels of ANF, TGFβ1, CTGF, collagen I, collagen III and phosphorylated ERK1/2 were lower, and expression of PPARγ was higher in ACE2KO mice in response to irbesartan treatment, without affecting cardiac expression of PPARα, PPARδ, β-myosin heavy chain, TGFβ2 and fibronectin.

Conclusions

We conclude that irbesartan prevents ACE2 deficiency-mediated pathological hypertrophy and myocardial fibrosis in ACE2 mutant mice via activation of the PPARγ signaling and suppression of the TGFβ−CTGF−ERK signaling, resulting in attenuation of myocardial injury. Drugs targeting ACE2 and PPARγ represent potential candidates to prevent and treat myocardial injury and related cardiac disorders.
Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease
Authors: Weiss Dustin J , Casale George P , Koutakis Panagiotis , Nella Aikaterini A , Swanson Stanley A , Zhu Zhen , Miserlis Dimitrios , Johanning Jason M , Pipinos Iraklis I
Published: September 2013

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in arteries supplying the legs, affects an estimated 27 million people in Europe and North America. Increased production of reactive oxygen species by dysfunctional mitochondria in leg muscles of PAD patients is viewed as a key mechanism of initiation and progression of the disease. Previous studies demonstrated increased oxidative damage in homogenates of biopsy specimens from PAD gastrocnemius compared to controls, but did not address myofiber-specific damage. In this study, we investigated oxidative damage to myofibers as a possible cause of the myopathy of PAD. To achieve this, we developed and validated fluorescence microscopy procedures for quantitative analysis of carbonyl groups and 4-hydroxy-2-nonenal (HNE) adducts in myofibers of biopsy specimens from human gastrocnemius. PAD and control specimens were evaluated for differences in 1) myofiber content of these two forms of oxidative damage and 2) myofiber cross-sectional area. Furthermore, oxidative damage to PAD myofibers was tested for associations with clinical stage of disease, degree of ischemia in the affected leg, and myofiber cross-sectional area. Carbonyl groups and HNE adducts were increased 30% (p < 0.0001) and 40% (p < 0.0001), respectively, in the myofibers of PAD (N = 34) compared to control (N = 21) patients. Mean cross-sectional area of PAD myofibers was reduced 29.3% compared to controls (p < 0.0003). Both forms of oxidative damage increased with clinical stage of disease, blood flow limitation in the ischemic leg, and reduced myofiber cross-sectional area. The data establish oxidative damage to myofibers as a possible cause of PAD myopathy.
Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors
Authors: Bali Kiran Kumar , Venkataramani Varun , Satagopam Venkata P , Gupta Pooja , Schneider Reinhard , Kuner Rohini
Published: September 2013

Background

Cancer-associated pain is a major cause of poor quality of life in cancer patients and is frequently resistant to conventional therapy. Recent studies indicate that some hematopoietic growth factors, namely granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF), are abundantly released in the tumor microenvironment and play a key role in regulating tumor-nerve interactions and tumor-associated pain by activating receptors on dorsal root ganglion (DRG) neurons. Moreover, these hematopoietic factors have been highly implicated in postsurgical pain, inflammatory pain and osteoarthritic pain. However, the molecular mechanisms via which G-/GMCSF bring about nociceptive sensitization and elicit pain are not known.

Results

In order to elucidate G-/GMCSF mediated transcriptional changes in the sensory neurons, we performed a comprehensive, genome-wide analysis of changes in the transcriptome of DRG neurons brought about by exposure to GMCSF or GCSF. We present complete information on regulated genes and validated profiling analyses and report novel regulatory networks and interaction maps revealed by detailed bioinformatics analyses. Amongst these, we validate calpain 2, matrix metalloproteinase 9 (MMP9) and a RhoGTPase Rac1 as well as Tumor necrosis factor alpha (TNFα) as transcriptional targets of G-/GMCSF and demonstrate the importance of MMP9 and Rac1 in GMCSF-induced nociceptor sensitization.

Conclusion

With integrative approach of bioinformatics, in vivo pharmacology and behavioral analyses, our results not only indicate that transcriptional control by G-/GMCSF signaling regulates a variety of established pain modulators, but also uncover a large number of novel targets, paving the way for translational analyses in the context of pain disorders.