bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Relative Roles of Pharmacogenetics and Ontogeny in Pediatric Drug Development and Regulatory Science
Authors: Leeder J. Steven , Kearns Gregory L. , Spielberg Stephen P. , van den Anker John
Published: February 2010

Understanding the dose‐exposure‐response relationship across the pediatric age spectrum from preterm and term newborns to infants, children, adolescents, and adults is a major challenge for clinicians, pharmaceutical companies, and regulatory agencies. Over the past 3 decades, clinical investigations of many drugs commonly used in pediatric therapeutics have provided valuable insights into age‐associated differences in drug disposition and action. However, our understanding of the contribution of genetic variation to variability in drug disposition and response in children generally has lagged behind that of adults. This article proposes a systematic approach that can be used to assess the relative contributions of ontogeny and genetic variation for a given compound. Application of the strategy is illustrated using the current regulatory dilemma posed by the safety and effectiveness of over‐the‐counter cough and cold remedies as an example. The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design.
Comparing Intra-Familial and Extra-Familial Child Sexual Abusers With Professionals Who Have Sexually Abused Children With Whom They Work
Authors: Sullivan Joe , Beech Anthony R. , Craig Leam A. , Gannon Theresa A.
Published: February 2010

The aim of this study is to establish whether professionals who have sexually molested children with whom they work present as a homogeneous group identifiable by their personal histories, offending patterns, and profiles as distinct from other child molesters (intra-familial and extra-familial offenders). Participants were matched on age and IQ. It was found that child molesters who were professionals (similar to extra-familial offenders generally) were likely to have sexually abused male, or both male and female, children and had abused more than 20 child victims. Professionals were also significantly more likely to have offended against post-pubescent children than were extra-familial or intra-familial offenders. In terms of psychological profiles, professionals, like extra-familial offenders, were found to have a significantly higher level of reported sexual pre-occupation and emotional over-identification with children compared with intra-familial offenders and a significantly lower level of distorted sexual attitudes about their victims compared with extra-familial offenders. These results are discussed in the context of assessment that might be used to assess risk in those working with children in a professional capacity.
Derivation of Transfer Function of an IPMC Actuator Based on Pseudo-Rigid Body Model
Authors: Bandopadhya Dibakar
Published: February 2010

In this article an effort has been made to derive the transfer function of an ionic polymer metal composite (IPMC) actuator. The transfer function obtained is based on the experimental deflection data and following the pseudo-rigid modeling technique. Initially an experiment is conducted with an IPMC actuator to measure its bending characteristics with input voltages. Subsequently expression for bending moment with radius of curvature is established. IPMC has been modeled then following the pseudo-rigid body modeling technique as fix-pin support type of cantilever mode with end-moment loading and its derivation is explained in detail. Based on the experimentally obtained bending moment, IPMC has been modeled to obtain the distributed force, spring constants, characteristic radius factor, and pseudo-rigid body angles. Energy based dynamic model of the IPMC actuator has been formulated following the Lagrangian principle based on the tip position in 2D. Transfer function is then obtained with respect to pseudo-rigid body angle and input voltage. Simulations have been performed to demonstrate the system response.
Security Sector Governance in South Asia
Authors: Banerjee Dipankar
Published: February 2010

The security sector encompasses those institutions and organisations in the government structure that are responsible for the security of the State and its citizens from external or internal threats. Minimally, these include military and paramilitary forces, the intelligence services, national and local police services, border, customs and coast guards. In order to reduce the risk of conflict, ensure sustainable peace, provide security for citizens and create the right environment for sustainable development, the existence of a capable, responsible and accountable security sector is critical. Effective security sector governance (SSG) involves the optimum management of security institutions within accepted norms of transparency, accountability and observance of humanitarian laws. Transparency and accountability are particularly challenging issues in South Asia. Mistakes made in the past can be avoided if today’s democratic governments were to address security issues constructively, by understanding one another’s security sectors and sharing knowledge of governance procedures and lessons learnt.
The Security Sector in Afghanistan
Authors: Murray Tonita
Published: February 2010

The article presents an overview of the post-Taliban status of the security sector in Afghanistan, particularly the Afghan National Army and police, the courts and judiciary, prisons and security intelligence elements of the security sector. It is argued that uneven distribution of international funding means uneven reform and that if one part of the security sector is neglected in favour of another, all security reform is affected because the institutions are inter-connected. International reform and Western security models are useful but ultimately limited. They can bring about ‘hardware’ changes but the ‘software’ changes of culture, values and behaviour can be made only from within. Situating Afghanistan in the historical, cultural and religious context of South Asia and drawing its reform models from this region might be ultimately more effective for the future of Afghan security sector reform than what the present reform phase allows.
Security Sector Reforms in Nepal
Authors: Pandey Nishchal N.
Published: February 2010

Nepal’s security sector is in a state of transition: from an old structural hierarchy in the security, judicial and administrative sectors to a security apparatus that is more democratic, transparent and accountable to the people. While security sector reforms (SSR) are crucial for the political stability of the country, SSR can be successfully implemented only when integrated into the larger government planning framework. To this end, any SSR programme will have to address important issues such as the reform of the Nepal Army (NA), which is perhaps the most important actor in Nepal’s security landscape; integration of former Maoist rebels into the NA; and strengthening the Nepal Police and Armed Police Force (APF). Additionally, successful SSR implementation will require the drawing up of a national security policy for Nepal and the adoption of a holistic approach to safeguarding its security interests.
Resistance to Reform; Submission to Status Quo
Authors: Cave Rosy , Manoharan N.
Published: February 2010

Security sector reform (SSR) in conflict-ridden countries like Sri Lanka is a challenging task. Currently, the inclination towards the reform process is scant. Apart from absence of political will, there is an immense deficit of institutional and human resources needed to carry out the requisite reforms. However, presence of some positive elements like keenness of international actors in motivating reforms and the inherent democratic nature of the country are encouraging. The article concludes that reforms in the security sector require a serious re-look at establishing a favourable security environment in the long run. To expect peace to stabilise a society without reforming the security sector is wishful thinking.
Profiling the Lashkar-e-Taiba
Authors: Zaidi Syed Manzar Abbas
Published: February 2010

This article profiles the Lashkar-e-Taiba, the Pakistani Jihadist organisation held responsible for the December 2008 terror attacks in Mumbai, India. The article elucidates the ideology, strategic objectives, evolution, organisational structure and methods of indoctrination and training of the organisation. These need to be comprehended in the context of the LeT’s terrorist capability. Evidence is given from Jihadist discourse from the Mujallul ud Dawa, the official publication of the LeT.
Contours of Deepening Financial Globalization in the Emerging Market Economies
Authors: Das Dilip K.
Published: February 2010

This article focuses on the financial globalization of the emerging market economies (EMEs) and the important differences across countries and country groups in this regard, particularly in the relative importance of different types of capital inflows and the pace of financial globalization. That the extent of financial globalization in the EMEs is both qualitatively and quantitatively different from the other country groups can be established with the help of the de jure and de facto measures. The author provides details of global private capital flows to the EMEs since the early 1970s. The following time period has been divided into various sub-periods. The characteristic features and trends for each period have been identified and analyzed.
Ireland’s low corporation tax: the case for tax coordination in the Union
Authors: Sweeney Paul
Published: February 2010

Ireland has been an innovator in using taxation as a tool for industrial policy, by attracting foreign direct investment (FDI) with low taxes on corporate profits. This article outlines the background to how this policy evolved and the advantage it was to building up Ireland’s industrial base during the 1990s as well as how it contributed to building the ‘Celtic Tiger’ economy from 1994 to 2000. It argues that, since EU enlargement in 2004, the advantages of using low corporate tax rates to attract FDI have diminished, even though ‘official’ and ‘corporate’ Ireland continue to promote this policy and to obstruct any EU-level moves to coordinate corporate tax. The room for manoeuvre is closing and it is argued that Ireland needs to develop alternative strategies and to engage seriously with its EU partners in finding agreement on a common corporate tax base.
The case against corporation tax harmonisation and tax-base consolidation: a view from Ireland
Authors: Barry Frank
Published: February 2010

Direct taxation remains within the competence of EU Member States. Some analysts argue, however, that differing corporation tax regimes lead to a ‘race to the bottom’, suggesting that tax harmonisation would be beneficial for the EU as a whole. This article evaluates the strength of this argument and considers the question of whether tax-base consolidation would be likely to lead inexorably to the harmonisation of tax rates.
The ‘pleasure citizen’
Authors: Riley Sarah , More Yvette , Griffin Christine
Published: February 2010

In this article, we explore the potential for leisure as a site for new forms of political participation. Using electronic dance music culture (EDMC) as an example, we locate our analysis within theories of neo-liberalism and neo-tribalism, both of which suggest that political participation may be occurring at an informal level through consumption. Interview and focus group data on participation in EDMC in the southwest of England were analyzed, producing the themes of ‘community, sociality and belonging’, ‘hedonism’, ‘multiplicity and flux’ and ‘Sovereignty’. These themes provided evidence for EDMC as a site for neo-tribal social and political participation, in which people created local and informal spaces of au-tonomy characterized by a celebration of community, sociality and hedonism. However, participants also drew on neo-liberal discourses of individualism, rights and responsibilities to make sense of their participation in EDMC, producing a move from economic and consumer citizen subjects to the ‘pleasure’ citizen.
Buy Nothing Day in Japan
Authors: Vinken Henk , Diepstraten Isabelle
Published: February 2010

Buy Nothing Day (BND) in Japan is a case for connecting notions on individual-ization of life courses and emerging forms of civic engagement. Based on interviews with BND Japan participants, we will see who participates and why. Moreover, we will explore how this participation interacts with the Japanese context. The highly educated participants of BND are well aware of the notions of seeking and shaping their own path in life, including civic life, and especially of doing so in a loose network of like-minded others. They are uncomfortable to define themselves in a one-dimensional way. There are three categories of motives to participate in BND Japan. The participants appreciate loosely structured, lifestyle-oriented and spontaneous activism. Also, they reflect Japanese cultural and structural conditions by, especially, separating their lives, identities and activism from the ‘world above’, the polity in Japan. It is complicated in Japan to present an ‘authentic self’ in one’s lifestyle that is stable and noticeable across roles, situations or contexts if one does not want to risk exclusion.
Peace out to revolution! Activism among African American youth
Authors: Ginwright Shawn A.
Published: February 2010

The purpose of this article is to explore new forms of activism among African American youth in the post-civil rights America. Dramatic educational, economic, political and cultural transformations in urban America, coupled with decades of unmitigated violence, have shaped both the constraints and opportunities for activism among black youth and the communities in which they live. The central argument throughout this article is that intensified oppression in urban communities (job loss, unmitigated violence and substance abuse) has threatened the type of community spaces that foster revolutionary hope and radical imaginations for African American youth. Restoring hope requires a radical healing, which is a dramatic departure from radical identity politics of the 1960s and 1970s. Radical healing involves building the capacity of young people to create this type of communities in which they want to live. This article argues for an alternative framework to understand black political and civic life among youth.
Visuo-proprioceptive training reduces risk of falls in patients with multiple sclerosis
Authors: Prosperini Luca , Leonardi Laura , De Carli Paolo , Mannocchi Maria Letizia , Pozzilli Carlo
Published: February 2010

Lack of balance and falls are common and disabling symptoms of multiple sclerosis. The aim of this study was to investigate the effectiveness of a novel visuo-proprioceptive feedback training in ameliorating balance and reducing the risk of falls. Patients with multiple sclerosis with unrestricted walking ability and healthy age/sex-matched controls were recruited. After a baseline clinical evaluation, including a postural assessment in double- (stabilometric test) and single-leg stance (monopodalic test) by a computerized postural recorder device, patients were submitted to a run-in period lasting 6 weeks without any rehabilitative intervention. Two further clinical and postural evaluations before and after a 6-week period of training were performed. The training protocol provided static and dynamic exercises both in double- and single-leg stance, with and without a translating Freeman-like board. Visual feedback was shown on the computer screen during the exercises.

We recruited 40 consecutive patients and 12 controls. Patients had significantly poorer postural performances than controls. Twenty-eight patients completed the study follow-up. No significant changes in risk of falls emerged after the run-in period. A significant reduction in the median percentage of risk of falls in single-leg stance (open eyes: 39.3 versus 15.7; closed eyes: 67.3 versus 52.6; p < 0.001, respectively) were observed after rehabilitation. Moreover, an improvement in walking speed (median time: 7.4 s versus 6.3; p = 0.001) was detected in the absence of Expanded Disability Status Scale changes. We conclude that visuo-proprioceptive training improves balance and reduces falls in multiple sclerosis.
Pedagogy, values and career fulfilment: evaluation of a science CPD programme
Authors: Doyle Seán
Published: February 2010

This article explores the potential of a residential Continuing Professional Development (CPD) model to promote sustained constructive dialogue between science educators, both on knowledge and pedagogy, and impact on teaching practice in a wide geographical area. It is based on a science education initiative shared by the local authorities in Scotland. These wider outcomes tend not to be planned for or evaluated (Guskey, 2000; Muijs et al., 2004; Wilson and Berne, 1999) in many CPD projects. This article examines these impacts and the model designed to deliver them through `training the trainer' approaches and enhanced career progression. Although the residential training of trainers model may seem relatively expensive, this article argues that it may be more cost-effective due to its greater impact on teaching than other CPD models. It encourages collaboration, dialogue and ongoing evaluation, and creates opportunities for teachers and researchers to build longer term collaborative networks in an attempt to explore actual, and not merely predicted, impacts of training on pedagogy and professional development (Wilson and Berne, 1999).
Is subject knowledge the be all and end all? Investigating professional development for science teachers
Authors: Woolhouse Clare , Cochrane Matt
Published: February 2010

This article reports on the initial findings of research carried out with a cohort of science teachers engaged in a professional development course at a northwest England university. The aim was to investigate how professional development was perceived by participants and explore the experiences of those who undertook the course. Results suggest that initially a utilitarian discourse which framed professional development as needing to fulfil identified needs, and an alignment of the benefits of undertaking professional development with training for quantifiable career advancement, took precedence over personal growth. However, as the course developed, the teachers began to recognize their integration into a professional learning community, and also saw the course as an opportunity for self-development. We suggest that a utilitarian paradigm can sit alongside a purpose which seeks to develop teachers' self-reflection and personal growth as a route to enrichment of pupil experience rather than focused on producing quantifiable progress in examination results.
Enabling students to participate in school improvement through a Students as Researchers programme
Authors: Roberts Amanda , Nash Judith
Published: February 2010

This article explores students' potential to make a difference to their school through a Students as Researchers programme. It begins by discussing the impetus for the current increase in student voice initiatives in schools. It continues the debate around issues of student empowerment and students' identity as change agents through an analysis of the development of a Students as Researchers (SAR) programme designed to support school improvement. The article investigates the possibilities for impact offered by a stepped approach to the student research process, early planning for impact and a strong student/teacher partnership. Issues are illuminated though reference to the authors' work with Students as Researchers groups in several UK schools. The article concludes with an exploration of ways of enhancing the impact of students' work on the development of their schools.
All-Day Recordings to Investigate Vocabulary Development: A Case Study of a Trilingual Toddler
Authors: Kimbrough Oller D.
Published: February 2010

Major innovations are becoming available for research in language development and disorders. Among these innovations, recent tools allow naturalistic recording in children’s homes and automated analysis to facilitate representative sampling. This study employed all-day recordings during the 2nd year of life in a child exposed to three languages, using a fully wearable battery-powered recorder, with automated analysis to locate appropriate time periods for coding. This method made representative sampling possible and afforded the opportunity for a case study indicating that language spoken directly to the child had dramatically more effect on vocabulary learning than audible language not spoken to the child, as indicated by chi-square analyses of the child’s verbal output and input in each of the languages. The work provides perspective on the role of learning words by overhearing in childhood and suggests the value of representative naturalistic sampling as a means of research on vocabulary acquisition.
Pre- and Postoccupancy Evaluation of New Dementia Care Cottages
Authors: Smith Ronald , Mathews R. Mark , Gresham Meredith
Published: February 2010

Concerns about negative outcomes associated with relocating residents are common. Fifty-five residents of a traditional high-care nursing home moved to new, purpose-built, dementia-specific cottages; 35 additional residents moved into the cottages within the first 8 months of operation. Direct-care staff participated in workshops on engaging residents in life-skill activities. Resident behavior was observed using a time sampling and a de-identified behavior mapping procedure. Results showed increases in resident engagement following the move and further increases after staff training. Staff engagement in resident interactive tasks similarly increased both after the move and again after staff training. The newly built cottages scored higher across all domains of 3 different types of environmental assessment, and family satisfaction ratings also improved. These results suggest that relocation need not negatively affect residents with dementia and that this environment provides an attractive model of care for dementia facilities.
Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways
Authors: Kheng Leong Ooi  , Tengku Sifzizul Tengku Muhammad  , Chui Hun Lim  , Shaida Fariza Sulaiman
Published: February 2010

The chloroform extract of Physalis minima produced a significant growth inhibition against human T-47D breast carcinoma cells as compared with other extracts with an EC50 value of 3.8 µg/mL. An analysis of cell death mechanisms indicated that the extract elicited an apoptotic cell death. mRNA expression analysis revealed the coregulation of apoptotic genes, that is, c-myc , p53, and caspase-3. The c-myc was significantly induced by the chloroform extract at the earlier phase of treatment, followed by p53 and caspase-3. Biochemical assay and ultrastructural observation displayed typical apoptotic features in the treated cells, including DNA fragmentation, blebbing and convolution of cell membrane, clumping and margination of chromatin, and production of membrane-bound apoptotic bodies. The presence of different stages of apoptotic cell death and phosphatidylserine externalization were further reconfirmed by annexin V and propidium iodide staining. Thus, the results from this study strongly suggest that the chloroform extract of P minima induced apoptotic cell death via p53-, caspase-3 -, and c-myc-dependent pathways.
Tocotrienols Inhibited Growth and Induced Apoptosis in Human HeLa Cells Through the Cell Cycle Signaling Pathway
Authors: Wu Shu-Jing , Ng Lean-Teik
Published: February 2010

Tocotrienols of palm oil have been shown to possess potent neuroprotective, antioxidative, anticancer, and cholesterol-lowering activities. In this study, the authors examined the antiproliferative effects of α-, γ- and δ-tocotrienols (αT3, γT3, and δT3), and α-tocopherol (αT) in human cervical carcinoma (HeLa) cells. Their mechanism(s) of action on cell cycle signaling pathway were also investigated. Results showed that the antiproliferative effect of αT3 (IC50: 3.19 ± 0.05 µM) and γT3 (IC 50: 2.85 ± 0.07 µM) was more potent than δT3 (IC 50: >100 µM) and αT (IC50: 69.46 ± 3.01 µM). Both αT3 and γT3 also demonstrated a dose-dependent and time-dependent induction of cell death.They caused cell cycle arrest at G2/M phase and triggered apoptosis as displayed by the externalization of annexin V—targeted phosphatidylserine and accumulation of sub-G1 peak. At a concentration of 3 µM, αT3 downregulated the expression of cyclin D3, p16, and CDK6, while having no effect on cyclin D1, p15, p21, p27, and CDK4 expression. However, γT3 showed no effect on these proteins. The induction of HeLa cell apoptosis by αT3 and γT3 appeared to be associated with the expression of IL-6, but not the other cytokines (IFN-γ, IL-2, and IL-10).Taken together, the results suggest that αT3 and γT3 are more effective than δT3 and αT in inhibiting HeLa cell proliferation, and their mode of action could be through the upregulation of IL-6, and the downregulation of cyclin D3, p16, and CDK6 expression in the cell cycle signaling pathway.
Relative Biological Effectiveness and Cell-Killing Efficacy of Continuous Low-Dose-Rate 125I Seeds on Prostate Carcinoma Cells In Vitro
Authors: Anyan Liao  , Junjie Wang  , Jidong Wang  , Hongqing Zhuang  , Yong Zhao
Published: February 2010

The aim of this study was to determine the effects of 125I seeds on prostate carcinoma (PC3) cells. The relative biological effectiveness of 125I seeds on PC3 cells with respect to 60Co γ rays was 1.4. Both 4 Gy of 60Co γ ray and 125I seed irradiation increased the percentage of cells in G2 phase, but there was no significant difference between these 2 types of radiation. Significantly, 125I seeds induced higher apoptotic rates of PC3 cells compared with 60Co γ ray irradiation. Furthermore, Bcl-2 expression, but not caspase-3 activity, in PC3 cells was downregulated after irradiation with 125I seed or 60Co γ rays.
Wake-Up Test Decrease Shunts Insertion During Carotid Endarterectomy Under General Anesthesia
Authors: Vetrugno Luigi , Di Luca Elena , Drigo Daniela , Fregonese Valtiero , Gonano Nevio , Giordano Francesco
Published: February 2010

Objective: The use of locoregional anesthesia versus general anesthesia (GE) in carotid endarterectomy (CEA) has been a debatable issue in clinical studies for the past several years. In our study, GE with wake-up tests (WUTs) during carotid cross-clamping was used instead of stump pressure (SP) to directly assess the neurological status of the patient to determine whether shunting was needed. Our study assessed the percentage of patients under light sedation and mechanically ventilated needing shunting based on WUT compared to a systolic stump pressure (SPs) cutoff value of ≤40 mm Hg. Design: Retrospective, observational study. Setting: University hospital clinic. Participants: Three hundred fifty-one patients (American Society of Anesthesiologists physical class II-III) with carotid artery stenosis scheduled for CEA under GE. Interventions: The WUT was used to assess the neurological status in patients undergoing CEA, which involved the gradual reduction of depth of anesthesia until the patient was capable of responding to a verbal stimulus and provide full collaboration while only receiving remifentanil. A positive WUT indicated that patient was not able to carry out the order. Measurements and Main Results: Of 343 patients, 20 (5.8%) were shunted due to a positive WUT after cross-clamping in comparison to 45 patients (12.8%) based on the SPs ≤40 mm Hg criteria. Conclusion: Wake-up test can be used to directly assess the neurological status in patients undergoing CEA to determine whether shunting is required. Our results showed that less patients required shunting based on WUT compared to the SP criteria.
From Edutainment to Serious Games: A Change in the Use of Game Characteristics
Authors: Charsky Dennis
Published: February 2010

Serious games use instructional and video game elements for nonentertainment purposes. Serious games attempt to create instructionally sound and relevant learning experiences for a wide variety of audiences and industries. The author contends that for serious games to be effective, instructional designers and video game designers need to understand how the game characteristics, competition and goals, rules, challenges, choices, and fantasy, used in both edutainment and serious games, can influence motivation and facilitate learning.
Pins and Rubber Traction System for Intra-Articular Proximal Interphalangeal Joint Fractures Revisited
Authors: Debus G. , Courvoisier A. , Wimsey S. , Pradel P. , Moutet F.
Published: February 2010

The Pins and Rubber Traction System (PRTS) can be used to treat proximal interphalangeal intra-articular fractures. Our experience is that outcomes are not always excellent and that many patients have reduced joint function or residual deformities. The aim of this study was to evaluate the reasons behind the poorer outcomes of some of the patients treated with this system. A retrospective clinical and radiological evaluation was performed on 15 patients after a minimum of 2 years’ follow-up. The mean interphalangeal joint flexion range was 66° (range 0—100) in our series. The review of the literature shows an average active interphalangeal joint flexion of 78° (range 64—95). Reasons for this difference include preoperative delay, technical deficiencies, the learning curve, a lack in postoperative physiotherapy and degenerative changes due to the longer follow-up. Although the Pins and Rubber Traction System seems a simple procedure, a learning curve is necessary to avoid pitfalls.
Outcomes of Nerve Reconstruction for Radial Nerve Injuries Based on the Level of Injury in 244 Operative Cases
Authors: Pan C.-H. , Chuang D.C.-C. , Rodríguez-Lorenzo A.
Published: February 2010

We report a single surgeon series of 244 patients with radial nerve injuries who had nerve repair, neurolysis, or nerve graft over a 17-year period. 44 patients had a Level I or infraclavicular injury, 37 had a Level II injury within the spiral groove of the humerus, 104 had a Level III injury from the lateral arm to antebrachial fossa and 64 had a Level IV injury affecting the posterior interosseous nerve. Nerve grafting was used most frequently in all groups, and was the only method of reconstruction for level II injury. At 21.5 months follow up, Level IV injuries had significantly better outcome of finger and thumb extension, while wrist extension recovered in at least 80% of the patients irrespective of the level of injury. The radial nerve recovered better if repaired or reconstructed within 5 months of injury.
Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching
Authors: Strasser Geraldine A. , Kaminker Joshua S. , Tessier-Lavigne Marc
Published: February 2010

The development of the vertebrate vascular system is mediated by both genetic patterning of vessels and by angiogenic sprouting in response to hypoxia. Both of these processes depend on the detection of environmental guidance cues by endothelial cells. A specialized subtype of endothelial cell known as the tip cell is thought to be involved in the detection and response to these cues, but the molecular signaling pathways used by tip cells to mediate tissue vascularization remain largely uncharacterized. To identify genes critical to tip cell function, we have developed a method to isolate them using laser capture microdissection, permitting comparison of RNA extracted from endothelial tip cells with that of endothelial stalk cells using microarray analysis. Genes enriched in tip cells include ESM-1, angiopoietin-2, and SLP-76. CXCR4, a receptor for the chemokine stromal-cell derived factor-1, was also identified as a tip cell-enriched gene, and we provide evidence for a novel role for this receptor in mediating tip cell morphology and vascular patterning in the neonatal retina.
Azithromycin induces anti-viral responses in bronchial epithelial cells
Authors: Gielen V. , Johnston S.L. , Edwards M.R.
Published: February 2010

The majority of asthma exacerbations are caused by rhinovirus. Currently the treatment of asthma exacerbations is inadequate. Previous evidence suggests that macrolide antibiotics have anti-inflammatory and antiviral effects; however, the mechanism is unknown.

We investigated the anti-rhinoviral potential of macrolides through the induction of antiviral gene mRNA and protein. Primary human bronchial epithelial cells were pre-treated with the macrolides azithromycin, erythromycin and telithromycin, and infected with minor-group rhinovirus 1B and major-group rhinovirus 16. The mRNA expression of the antiviral genes, type I interferon-β and type III interferon-λ1, interferon-λ2/3, and interferon-stimulated genes (retinoic acid inducible gene I, melanoma differentiation associated gene 5, oligoadenylate synthase, MxA and viperin) and pro-inflammatory cytokines (interleukin (IL)-6 and IL-8), and rhinovirus replication and release were measured.

Azithromycin, but not erythromycin or telithromycin, significantly increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon-stimulated gene mRNA expression and protein production. Furthermore, azithromycin significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6 and IL-8 protein and mRNA expression were not significantly reduced by azithromycin pre-treatment.

In conclusion, the results demonstrate that azithromycin has anti-rhinoviral activity in bronchial epithelial cells and, during rhinovirus infection, increases the production of interferon-stimulated genes.
Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial
Authors: Keranis E. , Makris D. , Rodopoulou P. , Martinou H. , Papamakarios G. , Daniil Z. , Zintzaras E. , Gourgoulianis K.I.
Published: February 2010

Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients.

The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)).

The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time.

These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.
Socioeconomic risk factors for lung function decline in a general population
Authors: Johannessen A. , Eagan T.M.L. , Omenaas E.R. , Bakke P.S. , Gulsvik A.
Published: February 2010

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population.

In the Hordaland County Cohort Study, 1,644 subjects aged 26–82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996–1997 and in 2003–2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC.

Mean annual decline in FEV1from baseline to follow-up was 57 mL (se1.3) and 48 mL (se1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV1/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV1(adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL).

Low SES was associated with increased lung function decline in males. For females, marital status was more important.
Reduction of oxidative cellular damage by overexpression of the thioredoxin TRX2 gene improves yield and quality of wine yeast dry active biomass
Authors: Gómez-Pastor Rocío , Pérez-Torrado Roberto , Cabiscol Elisa , Ros Joaquim , Matallana Emilia
Published: February 2010

Background

Wine Saccharomyces cerevisiae strains, adapted to anaerobic must fermentations, suffer oxidative stress when they are grown under aerobic conditions for biomass propagation in the industrial process of active dry yeast production. Oxidative metabolism of sugars favors high biomass yields but also causes increased oxidation damage of cell components. The overexpression of the TRX2 gene, coding for a thioredoxin, enhances oxidative stress resistance in a wine yeast strain model. The thioredoxin and also the glutathione/glutaredoxin system constitute the most important defense against oxidation. Trx2p is also involved in the regulation of Yap1p-driven transcriptional response against some reactive oxygen species.

Results

Laboratory scale simulations of the industrial active dry biomass production process demonstrate that TRX2 overexpression increases the wine yeast final biomass yield and also its fermentative capacity both after the batch and fed-batch phases. Microvinifications carried out with the modified strain show a fast start phenotype derived from its enhanced fermentative capacity and also increased content of beneficial aroma compounds. The modified strain displays an increased transcriptional response of Yap1p regulated genes and other oxidative stress related genes. Activities of antioxidant enzymes like Sod1p, Sod2p and catalase are also enhanced. Consequently, diminished oxidation of lipids and proteins is observed in the modified strain, which can explain the improved performance of the thioredoxin overexpressing strain.

Conclusions

We report several beneficial effects of overexpressing the thioredoxin gene TRX2 in a wine yeast strain. We show that this strain presents an enhanced redox defense. Increased yield of biomass production process in TRX2 overexpressing strain can be of special interest for several industrial applications.
Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats
Authors: Runyon Michael S , Gellar Michael A , Sanapareddy Nina , Kline Jeffrey A , Watts John A
Published: February 2010

Background

Experimental models of pulmonary embolism (PE) that produce pulmonary hypertension (PH) employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD) and Copenhagen (Cop) rats can produce persistent PH.

Methods

blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days.

Results

Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours) and 97% (5 days) in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days). Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation.

Conclusions

Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.
Expression Genetics Identifies Spinal Mechanisms Supporting Formalin Late Phase Behaviors
Authors: Li Xiangqi , Sahbaie Peyman , Zheng Ming , Ritchie Jennifer , Peltz Gary , Mogil Jeffrey S , Clark J David
Published: February 2010

Background:

Formalin injection into rodent hind paws is one of the most commonly employed pain assays. The resulting nocifensive behaviors can be divided into two phases differing in timing, duration and underlying mechanisms. Spinal sensitization has long been felt to participate in the second phase of this response, although this sensitization is incompletely understood. By using correlative analysis between spinal gene expression and mouse strain-dependent intensity of late phase behavior, we hypothesized genes participating in variability of the response could be identified.

Results:

Late phase formalin behavior scores among 10 inbred mouse strains were correlated with a spinal cord gene expression database constructed using expression arrays. Messenger RNA levels for several genes were highly correlated with the late phase behavioral responses. Most of these genes had already been implicated in mechanisms regulating pain and analgesia. One of the most strongly correlated genes, Mapk8 coding for c-Jun N-terminal kinase 1 (JNK1), was chosen for further analysis. Studies using additional strains of mice confirmed that spinal cord mRNA expression levels of Mapk8 followed the pattern predicted by strain-specific levels of formalin behavior. Interestingly, spinal cord JNK1 protein levels displayed an inverse relationship with mRNA measurements. Finally, intrathecal injections of the selective JNK inhibitor, SP600125, selectively reduced late phase licking behavior.

Conclusions:

Wide differences in pain behaviors, including those resulting from the injection of formalin, can be observed in inbred strains of mice suggesting strong genetic influences. Correlating levels of gene expression in tissues established to be mechanistically implicated in the expression of specific behaviors can identify genes involved in the behaviors of interest. Comparing formalin late phase behavior levels with spinal cord gene expression yielded several plausible gene candidates, including the Mapk8 gene. Additional molecular and pharmacologic evidence confirmed a functional role for this gene in supporting formalin late phase responses.
Midgut pain due to an intussuscepting terminal ileal lipoma: a case report
Authors: Abbasakoor Noormuhammad O , Kavanagh Dara O , Moran Diarmaid C , Ryan Barbara , Neary Paul C
Published: February 2010

Introduction

The occurrence of intussusception in adults is rare. The condition is found in 1 in 1300 abdominal operations and 1 in 100 patients operated for intestinal obstruction. The child to adult ratio is 20:1.

Case presentation

A 52-year-old Irish Caucasian woman was investigated for a 3-month history of intermittent episodes of colicky midgut pain and associated constipation. Ileocolonoscopy revealed a pedunculated lesion in the terminal ileum prolapsing into the caecum. Computed tomography confirmed a smooth-walled, nonobstructing, low density intramural lesion in the terminal ileum with secondary intussusception. A laparoscopic small bowel resection was performed. Histology revealed a large pedunculated polypoidal mass measuring 4 × 2.5 × 2 cm consistent with a submucosal lipoma. She had complete resolution of her symptoms and remained well at 12-month follow-up.

Conclusion

This case highlights an unusual cause of incomplete small bowel obstruction successfully treated through interdisciplinary cooperation. Ileal lipomas are not typically amenable to endoscopic removal and require resection. This can be successfully achieved via a laparoscopic approach with early restoration of premorbid functioning.
Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial
Authors: Ng Norman TM , Heesch Kristiann C , Brown Wendy J
Published: February 2010

Introduction

Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA.

Methods

Thirty-six low active participants (aged 42 to 73 years) were provided with 1500 mg glucosamine sulphate per day for 6 weeks, after which they began a 12-week progressive walking program, while continuing to take glucosamine. They were randomized to walk 3 or 5 days per week and given a pedometer to monitor step counts. For both groups, step level of walking was gradually increased to 3000 steps/day during the first 6 weeks of walking, and to 6000 steps/day for the next 6 weeks. Primary outcomes included physical activity levels, physical function (self-paced step test), and the WOMAC Osteoarthritis Index for pain, stiffness and physical function. Assessments were conducted at baseline and at 6-, 12-, 18-, and 24-week follow-ups. The Mann Whitney Test was used to examine differences in outcome measures between groups at each assessment, and the Wilcoxon Signed Ranks Test was used to examine differences in outcome measures between assessments.

Results

During the first 6 weeks of the study (glucosamine supplementation only), physical activity levels, physical function, and total WOMAC scores improved (P < 0.05). Between the start of the walking program (Week 6) and the final follow-up (Week 24), further improvements were seen in these outcomes (P < 0.05) although most improvements were seen between Weeks 6 and 12. No significant differences were found between walking groups.

Conclusions

In people with hip or knee OA, walking a minimum of 3000 steps (~30 minutes), at least 3 days/week, in combination with glucosamine sulphate, may reduce OA symptoms. A more robust study with a larger sample is needed to support these preliminary findings.

Trial Registration

Australian Clinical Trials Registry ACTRN012607000159459.