bluuebunny/crossref_metadata_2025 huggingface dataset:
Loubards: 1980s French-Algerian activism and the conceptual limits of Beur scholarship
Authors: Cohen Kfir
Published: January 2013

Beur literature designates artistic production by the second generation of Algerian immigration to France, gaining attention after the 1983 ‘Marche pour l’égalité et contre le racism’. Since the late 1980s, French and American scholars working with postcolonial and poststructuralist theories have tended to situate Beur literary production vis-à-vis French identity and conceptualise it as a site of social critique. This scholarship sees in Beur literary production an instance of hybridisation and ambivalence, estranging French identity. Useful and necessary as it is, historicising the Beur might require rethinking this approach. Following early activists’ struggles that constituted in part the historic conditions of Beur identity reveals a heterogeneous field of competing identities and political strategies. Activists’ accounts suggest a process of identity centralisation in which Beur identity, as a cultural hybrid, rewrote other more radical positions and rendered them illegible. These struggles, revolving around questions of work and alternatives forms of social organisation, allow us, first, to recognise the fact that current Beur scholarship has been, for the most part, limited to a critique of the French state, and, second, to situate Beur history and Beur literature in the larger context of globalisation.
Art and the ‘Arab Spring’: Aesthetics of revolution in contemporary Tunisia
Authors: Shilton Siobhán
Published: January 2013

A striking proliferation of artwork has emerged in response to the Tunisian Revolution, following decades of censorship under the former president Zine el Abidine Ben Ali, who was forced to flee the country on 14 January 2011. Certain visual representations of the Tunisian Revolution employ the iconic language that has been utilised in revolutions in diverse historical and geographical contexts. However, many seek to avoid what the photographer Jellel Gasteli has dubbed ‘[des] icônes de l’exotisme révolutionnaire’. Drawing on postcolonial theory, this article argues that a still emerging corpus of artwork reveals an alternative ‘aesthetic of resistance’ with which to communicate the complexity and diversity of Tunisia. Such artwork forges a third way between totalising internal and external visions of the country. It presents a nuanced engagement with the Revolution, allowing – in distinctively visual or multisensorial ways – for ‘untranslatable’ voices or ‘unrepresentable’ visions of democracy in a universal sense.
Discursively constituted experience, or experience as reply: A rejoinder
Authors: Haye Andrés , Larrain Antonia
Published: January 2013

The goal of the paper is to briefly sketch a theoretical proposal about the role played by discourse in the texture and texturing of lived experience. Inspired by the work of Bakhtin, we develop implications of concepts of inner speech, dialogicality, and specially outsideness, disputing the idea that phenomenological approaches are well equipped to account for human experience. The main argument is that so-called “immediate” experience is discursively mediated and, as such, is constituted by a dialogical dynamic of co-affection. We raise the idea that the streams of experience consist in social and psychological movements of reply.
The reliability, validity and responsiveness of the Thai version of systemic lupus erythematosus quality of life (SLEQOL-TH) instrument
Authors: Kasitanon N , Wangkaew S , Puntana S , Sukitawut W , Leong KP ,   Tan Tock Seng Hospital Lupus Study Group, Louthrenoo W
Published: January 2013

Objectives

The English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) is a validated disease-specific quality of life instrument. The aim of this study was to evaluate the psychometric properties of the Thai version of the SLEQOL (SLEQOL-TH).

Methods

Two independent translators translated the SLEQOL into Thai. The back translation of this version was performed by two other independent translators. The final version, SLEQOL-TH, was completed after resolving the discrepancies revealed by the back translation. One hundred and nine patients with SLE were enrolled to test the reliability, construct validity, floor and ceiling effects, and sensitivity to the changes of the SLEQOL-TH at six months. The differential item functioning (DIF) between the Thai and English versions was analyzed using the partial gamma.

Results

The internal consistency of the SLEQOL-TH was satisfactory with the overall Cronbach’s alpha of 0.86. The test-retest reliability of the SLEQOL-TH was acceptable with the intra-class correlation coefficient of 0.86. Low correlations between the SLEQOL-TH and SLEDAI were observed. The total score of the SLEQOL-TH was moderately responsive to changes in quality of life, with a standardized response mean of 0.50. When comparing the SLEQOL-TH from Thai SLE patients with the original SLEQOL version obtained from Singapore SLE patients, 11 out of 40 items showed a moderate to large DIF.

Conclusions

The SLEQOL-TH has acceptable psychometric properties and shows construct validity. In comparison with the English version of SLEQOL, there are some items that showed DIF. The applicability of the SLEQOL-TH in real-life clinical practice and clinical trials needs to be determined.
Annular subacute cutaneous lupus erythematosus lesions and polymyositis onset in a patient with primary Sjögren's syndrome: how should this unusual association be classified?
Authors: Bernacchi E , Neri R , Caproni M , Loggini B , Fabbri P , Bombardieri S
Published: January 2013

Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren’s syndrome (SS) is currently debated within the conventional SS criteria or as primary SS ( pSS) developing autoimmune disease or as ‘associated-overlap’ with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab.
Development of a Respite Care Program for Caregivers of Pediatric Oncology Patients and Their Siblings
Authors: Carter Kathryn Berry , Mandrell Belinda N.
Published: January 2013

Children with chronic health care needs, including those with cancer, require complex care under direct caregiver supervision. This intensive care management may result in increased stress and psychological distress for the caregiver and family. Respite care services are needed in providing alleviation of caregiver stress among families of children with complex health care needs. This report describes the feasibility of a pilot hospital-based respite care program for caregivers of pediatric oncology patients and their siblings and development of a permanent, expanded service to include both inpatient and outpatient units under the supervision of hospital volunteer services. During the feasibility pilot, 39 respite care requests were made by caregivers for care of patients, with 67% of these requests for care of infants and toddlers. The respite care providers were hospital volunteers. Reasons for the caregiver respite care request included a need to leave the hospital for running an errand, eating a meal, taking a mental break, or talking with the medical team. At the completion of the pilot, caregivers and staff were surveyed and expressed a strong desire for continuation of the service. The success of the pilot led to the implementation of a formal respite care program, Helping Hands, which provides services 7 days a week for inpatients, outpatients, and their siblings. Although this respite care service is specific to children with cancer, the program model is feasible within most pediatric care facilities.
Panic Disorder and Agoraphobia
Authors: Schmidt Norman B. , Norr Aaron M. , Korte Kristina J.
Published: January 2013

With the upcoming release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) there has been a necessary critique of the DSM-IV including questions regarding how to best improve the next iteration of the DSM classification system. The aim of this article is to provide commentary on the probable direction the DSM-V is headed with regard to panic attacks, panic disorder (PD), and agoraphobia (AG). The DSM-V Work Group’s recommendations for panic attacks, PD, and AG are reviewed, and important diagnostic questions and concerns are raised. Future research directions are discussed that will hopefully help improve our understanding of anxiety and our ability to accurately diagnose and classify these conditions.
The Prevalence and Importance of Crypt Apoptosis, Focal Active Cryptitis, and Neutrophilic Infiltrate of the Lamina Propria in Colorectal Adenomas
Authors: AbdullGaffar Badr , Hotait Hassan , Gopal Parthasarathi , Al-Awadhi Sameer , Bamakhrama Khaled , ElFaki Bashir
Published: January 2013

Even though apoptotic bodies (ABs) are frequent in colorectal adenomas, their relevance has been covered only in a few studies. Focal active cryptitis (FAC) is a well-known manifestation of several etiologies; however, its prevalence and significance in colonic adenomas were not scrutinized. Likewise, whether the neutrophilic infiltrate of the lamina propria (LP) in colonic adenomas has a clinical or pathologic significance was not previously studied. We attempted to investigate the prevalence and importance of ABs in the cryptal epithelium and of neutrophils in the form of FAC and in the form of LP infiltrates in conventional colorectal adenomas. We conducted a retrospective review study over a 6-year period. We collected 223 conventional adenomas from 156 patients. We studied the interrelationship between these 3 histologic parameters and their potential association with other clinical and pathologic variables. Comparison controls included normal colonic mucosa, hyperplastic polyps, serrated adenomas, and flat adenomas. We found 91 (41%) adenomas to have crypt apoptosis, 40 (18%) to have FAC, and 69 (31%) to have neutrophilic infiltrate of the LP. We found ABs to be more frequent in high-grade adenomas. LP neutrophilic infiltrate was significantly associated with high-grade adenomas and in high-grade adenomas with invasive foci. In contrast, FAC was not associated with high-grade adenomas and was secondary to bowel preparations and drugs. Crypt apoptosis and LP neutrophils might have a potential prognostic value in predicting the biologic behavior of colonic adenomas. FAC in adenomas is a nonspecific finding of no prognostic significance and is related to external stimuli.
Arthroscopic Excision of a Symptomatic Os Trigonum in a Lateral Decubitus Position
Authors: Park Chul Hyun , Kim Sung Yoon , Kim Jung Rae , Lee Woo Chun
Published: January 2013

Background:

The purpose of this study was to introduce our technique of arthroscopic excision of the os trigonum in the lateral decubitus position through anterolateral, centrolateral, and posterolateral portals and also to investigate the safety and clinical results of this technique.

Methods:

Between May 2007 and May 2011, 23 ankles of 23 consecutive patients underwent subtalar arthroscopic removal of the os trigonum in a lateral decubitus position. Twenty patients were male and 3 were female. All patients injured their ankles during sports activities. Mean duration of postoperative follow-up was 18 months, and no patients were lost to follow-up. Clinical evaluations were performed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the visual analog scale (VAS) for pain. The time to return to work and sports activities was assessed.

Results:

Average AOFAS ankle-hindfoot score increased from 71.3 (range, 59-85) preoperatively to 94.7 (range, 90-100) postoperatively, and VAS for pain decreased from 6.7 (range, 3-10) to 1.5 (range, 0-3). Average plantarflexion of the ankle increased from 28.8 degrees (range, 15-40) preoperatively to 42.5 degrees (range, 25-50) postoperatively. Mean time to resumption of sports activities was 6.7 weeks (range, 5-12). There were no major complications in any patient.

Conclusion:

Arthroscopic excision of a symptomatic os trigonum using anterolateral, centrolateral, and posterolateral portals in the lateral decubitus position was a safe and effective technique.

Level of Evidence:

Level IV, retrospective case series.
Varus and Valgus Foot in Cerebral Palsy and its Management
Authors: Root Leon
Published: January 2013

Varus and valgus foot, often associated with equinus, are common problems in cerebral palsy. These deformities can interfere with standing or walking, aggravate shoe wear, and lead to painful calluses on pressure areas of the foot. The deformities are caused by a basic muscle imbalance. If the posterior or anterior tibial muscles are overactive, the foot will swing into varus. If the peroneal muscles predominate, the foot assumes a valgus position. However, the alignment of the hip and knee play an important role in the production of deformity.

Correction of the deformity must be preceded by assessment of the deforming forces. In the younger child, simple muscle releases weaken the overpowering muscles and help restore muscle balance. In some instances, muscle transfers, either whole or split, not only alleviate the deforming force but also may provide needed support for the weaker muscles. Once bone deformities are established, they must be corrected either prior to or simultaneously with muscle procedures.

The purposes of this article is to outline the evaluation of the deformity and the various soft tissue and bone operations which can be performed to correct them in order to obtain a satisfactory plantigrade foot.
A Comparative Study of the Frequency of Anterior Impingement Exostoses of the Ankle in Dancers and Nondancers
Authors: Stoller Steven M. , Hekmat Farshid , Kleiger Barnard
Published: January 2013

True lateral roentgenograms were obtained in 100 nondancers and 32 professional dancers to determine the incidence of anterior talar exostoses. The average age of the nondancers was 45.8 years as compared to 23.0 years in the dancer population. Both groups were asymptomatic in the region of the foot and ankle. All exostoses on the dorsum of the talar neck measuring greater than 1 mm were recorded.
Occult Foreign Bodies of the Foot
Authors: Alfred Richard H. , Jacobs Richard
Published: January 2013

This article illustrates several case reports of occult foreign bodies of the foot. The patients came for treatment from weeks to years after the inciting incident with chronic, sterile, draining wounds. The diagnosis of these foreign bodies can be quite difficult. Several radiographic and clinical clues are included, yet the single most valuable tool for the physician remains a high index of suspicion.
Group Involvements in City Politics and Pluralist Theory
Authors: Schumaker Paul
Published: January 2013

The assessments of 75 councilors and mayors in eight cities in the Kansas City metropolitan area provide global measures of group organization, activity, and influence in community politics and measures of their specific involvements in 73 issues that arose in these communities. While variations in group involvement and influence—both in exercising social control and contributing to social production—are reported, the most general findings are that groups are less involved in city politics and their limited involvements are less conflictive than suggested by orthodox understandings of pluralist theory. I argue that these results point to the need to reformulate pluralist theory, not abandon it.
Assessing WAC Elements in Business Syllabi
Authors: Nicolas Maureen O’Day , Annous Samer
Published: January 2013

This study investigates syllabi for evidence of the principles of writing across the curriculum (WAC) in courses offered by the Faculty of Business (FOB) at a university operating in a non–English-speaking country. The research analyzed all syllabi of FOB courses offered in the spring 2010 semester for evidence of WAC looking for indications of writing activities. The analysis focused on both expressive/informal and product/formal writing and discovered through the syllabi the intention of the instructor to incorporate writing. The findings suggest that these courses require little or no writing and therefore principles of WAC are not evident.
Is there a home advantage in school readiness for young children? Trends in parent engagement in cognitive activities with young children, 1991–2001
Authors: Schaub Maryellen
Published: January 2013

The desire to understand the home advantage has spurred a large body of research describing the contribution of differences in family background and parenting styles to school readiness and the achievement gap. Using the National Household Education Survey at two time points provides a fuller picture of the trends in parenting and cognitive activities with young children before the onset of formal schooling. The results presented here show that although more educated parents participate more in cognitive activities with their young children in 1991 and 2001, participation is increasing for all parents. This is true for a widely expected parental activity, reading to your child, and for a direct instruction activity, teaching letters, words, and numbers. It is also true for the more creative activities of music, arts and crafts, and telling stories. Contrary to images of some families as deficient and others as overly exuberant, all families in this sample are increasing engagement with their young children in a range of cognitive activities aimed at school readiness because parents as well as children get socialized to the culture of schooling. Modern American schooling requires parents to be engaged in the education process of their children and attempt to create advantage for them.
Practices for Embedding an Interpretive Qualitative Approach Within a Randomized Clinical Trial
Authors: Plano Clark Vicki L. , Schumacher Karen , West Claudia , Edrington Janet , Dunn Laura B. , Harzstark Andrea , Melisko Michelle , Rabow Michael W. , Swift Patrick S. , Miaskowski Christine
Published: January 2013

The embedded approach is a mixed methods design that is most commonly used when qualitative methods are embedded within intervention designs such as randomized clinical trials (RCTs). Scholars have noted challenges associated with embedded procedures and expressed concern that embedded designs undervalue and underutilize interpretive qualitative approaches. This article examines these issues in the context of a study about cancer pain management where qualitative methods were embedded within an RCT design. We describe our practices for stating embedded research questions, designing embedded qualitative data collection within the constraints of the RCT, and developing enriched understandings of the RCT through an interpretive qualitative analysis. These practices provide guidance for intervention researchers planning to embed qualitative components within RCT designs.
Bayesian adaptive phase II screening design for combination trials
Authors: Cai Chunyan , Yuan Ying , Johnson Valen E
Published: January 2013

Background

Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents.

Methods

Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations.

Results

Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments.

Limitations

The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated.

Conclusions

The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial.
A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose
Authors: Taylor David , Lenox-Smith Alan , Bradley Andrew
Published: January 2013

Depression and anxiety disorders are among the most common disorders treated by general practitioners (GPs) in the UK. Since both disorders are associated with a significantly increased risk of suicide, including with antidepressant overdose, the safety of antidepressants in overdose is of paramount importance. Numerous updates relating to antidepressant safety have been issued by regulators in the UK which may have eroded GP confidence in antidepressants. Venlafaxine, a serotonin nor adrenaline reuptake inhibitor (SNRI) had primary care prescribing restrictions placed on it in 2004 due to concerns about cardiotoxicity and mortality in overdose. Although a review of the evidence led to a reversal of the majority of restrictions in 2006, evidence suggests GPs may still be cautious in their prescribing of venlafaxine and possibly other SNRI antidepressants for patients with depression and anxiety disorders. This paper reviews the evidence pertaining to the safety of SNRI antidepressants from a perspective of cardiovascular safety and overdose. The currently available evidence suggests a marginally higher toxicity of venlafaxine in overdose compared with another SNRI duloxetine and the selective serotonin reuptake inhibitors (SSRIs), although this may be related to differential patterns of prescribing in high-risk patients. Based on this review SNRIs have a positive risk benefit profile in the treatment of depression and generalized anxiety disorder in primary care, especially as second-line agents to SSRIs.
Ultrasound-Guided Regional Anesthesia in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Geriatric Trauma Patient
Authors: Födinger Agnes M. , Kammerlander Christian , Luger Thomas J.
Published: January 2013

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzymatic disorder causing hemolytic anemia. Exposure to drugs is considered to be the most common cause of acute hemolysis in patients with G6PD deficiency. Experience with regional anesthesia, in particular peripheral nerve blocks, is rarely described in patients with G6PD deficiency, but is of great clinical interest. For this reason, we now report on the successful management of ultrasound-guided axillary brachial plexus block in a patient with geriatric G6PD deficiency. Case report: A female, 75-year-old geriatric trauma patient with G6PD deficiency and a fracture of the left forearm, was scheduled for osteosynthesis of the left forearm. For surgery regional anesthesia with ultrasound-guided axillary brachial plexus block with 30 mL bupivacaine 0.5% was established. Surgical operation und postoperative course were uneventful and with no signs of hemolysis. Conclusion: Ultrasound-guided axillary brachial plexus block with bupivacaine was a safe and effective technique in this patient with G6PD deficiency. Peripheral nerve block is a major analgesic approach and of great value for anesthesiologists and surgeons, especially in our aging and multimorbid society.
Some results on the generalized Mittag-Leffler function operator
Authors: Prajapati JC , Jana RK , Saxena RK , Shukla AK
Published: January 2013

This paper is devoted to the study of a generalized Mittag-Leffler function operator introduced by Shukla and Prajapati (J. Math. Anal. Appl. 336:797-811, 2007). Laplace and Mellin transforms of this operator are investigated in this paper. Some special cases of the established results are also deduced as corollaries. The results obtained are useful where the Mittag-Leffler function occurs naturally.

MSC:33E12, 26A33, 44A45.
SOX11 contributes to the regulation of GDF5 in joint maintenance
Authors: Kan Akinori , Ikeda Toshiyuki , Fukai Atsushi , Nakagawa Takumi , Nakamura Kozo , Chung Ung-il , Kawaguchi Hiroshi , Tabin Clifford J
Published: January 2013

Background

Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis.

Results

Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5’ UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans.

Conclusions

This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.
The Holliday junction resolvase RecU is required for chromosome segregation and DNA damage repair in Staphylococcus aureus
Authors: Pereira Ana R , Reed Patricia , Veiga Helena , Pinho Mariana G
Published: January 2013

Background

The Staphylococcus aureus RecU protein is homologous to a Bacillus subtilis Holliday junction resolvase. Interestingly, RecU is encoded in the same operon as PBP2, a penicillin-binding protein required for cell wall synthesis and essential for the full expression of resistance in Methicillin Resistant S. aureus strains. In this work we have studied the role of RecU in the clinical pathogen S. aureus.

Results

Depletion of RecU in S. aureus results in the appearance of cells with compact nucleoids, septa formed over the DNA and anucleate cells. RecU-depleted cells also show increased septal recruitment of the DNA translocase SpoIIIE, presumably to resolve chromosome segregation defects. Additionally cells are more sensitive to DNA damaging agents such as mitomycin C or UV radiation. Expression of RecU from the ectopic chromosomal spa locus showed that co-expression of RecU and PBP2 was not necessary to ensure correct cell division, a process that requires tight coordination between chromosome segregation and septal cell wall synthesis.

Conclusions

RecU is required for correct chromosome segregation and DNA damage repair in S. aureus. Co-expression of recU and pbp2 from the same operon is not required for normal cell division.
Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells
Authors: Collins Hilary M , Abdelghany Magdy K , Messmer Marie , Yue Baigong , Deeves Sian E , Kindle Karin B , Mantelingu Kempegowda , Aslam Akhmed , Winkler G Sebastiaan , Kundu Tapas K , Heery David M
Published: January 2013

Background

Post-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7.

Methods

Cell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR.

Results

Although treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2, and was prevented by siRNA targeting of SUV420H2.

Conclusion

In summary, although garcinol and curcumin can both inhibit histone acetyltransferase activities, our results show that these compounds have differential effects on cancer cells in culture. Garcinol treatment alters expression of chromatin modifying enzymes in MCF7 cells, resulting in reprogramming of key histone and p53 PTMs and growth arrest, underscoring its potential as a cancer chemopreventive agent.
Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis
Authors: Zhu Jun , Li Te , Wang Xiaohui , Ye Ming , Cai Jian , Xu Yuejuan , Wu Bin
Published: January 2013

Background

Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear.

Methods

A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated.

Results

After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results.

Conclusions

These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.
How has the flu virus infected the Web? 2010 influenza and vaccine information available on the Internet
Authors: Covolo Loredana , Mascaretti Silvia , Caruana Anna , Orizio Grazia , Caimi Luigi , Gelatti Umberto
Published: January 2013

Background

The 2009–10 influenza pandemic was a major public health concern. Vaccination was recommended by the health authorities, but compliance was not optimal and perception of the presumed associated risks was high among the public. The Internet is increasingly being used as a source of health information and advice. The aim of the study was to investigate the characteristics of websites providing information about flu vaccine and the quality of the information provided.

Methods

Website selection was performed in autumn 2010 by entering eight keywords in two of the most commonly used search engines (Google.com and Yahoo.com). The first three result pages were analysed for each search, giving a total of 480 occurrences. Page rank was evaluated to assess visibility. Websites based on Web 2.0 philosophy, websites merely displaying popular news/articles and single files were excluded from the subsequent analysis. We analysed the selected websites (using WHO criteria) as well as the information provided, using a codebook for pro/neutral websites and a qualitative approach for the adverse ones.

Results

Of the 89 websites selected, 54 dealt with seasonal vaccination, three with anti-H1N1 vaccination and 32 with both. Rank analysis showed that only classic websites (ones not falling in any other category) and one social network were provided on the first pages by Yahoo; 21 classic websites, six displaying popular news/articles and one blog by Google. Analysis of the selected websites revealed that the majority of them (88.8%) had a positive/neutral attitude to flu vaccination. Pro/neutral websites distinguished themselves from the adverse ones by some revealing features like greater transparency, credibility and privacy protection.

Conclusions

We found that the majority of the websites providing information on flu vaccination were pro/neutral and gave sufficient information. We suggest that antivaccinationist information may have been spread by a different route, such as via Web 2.0 tools, which may be more prone to the dissemination of “viral” information. The page ranking analysis revealed the crucial role of search engines regarding access to information on the Internet.
Ultrasonic evaluation of the abductor hallucis muscle in hallux valgus: a cross-sectional observational study
Authors: Stewart Sarah , Ellis Richard , Heath Mike , Rome Keith
Published: January 2013

Background

The aim of the study was to investigate the abductor hallucis muscle characteristics, defined as dorso-plantar (DP) thickness, medio-lateral (ML) width, and cross-sectional area (CSA) in relation to the severity of hallux valgus using musculoskeletal ultrasound. One hundred and two feet, mean (SD) age of 60.3 (20.54) years old, displaying varying severities of hallux valgus were stratified into four groups representing the four grades of the Manchester Scale (grade 0: no deformity, grade 1: mild deformity, grade 2: moderate deformity and grade 3: severe deformity).

Methods

The abductor hallucis muscle was imaged in each foot using a portable ultrasound system. The mean (SD) DP thickness, ML width, and CSA measurements were compared across the four Manchester Scale grades using a one-way ANOVA.

Results

Significant differences in DP thickness were found between feet with no hallux valgus (grade 0) and feet with hallux valgus grade 2 (p = 0.001) and 3 (p < 0.001). Significant differences were also found in ML width between feet with no hallux valgus (grade 0) and feet with grade 2 hallux valgus (p = 0.010). Significant differences in CSA were found between feet with no hallux valgus (grade 0) and feet with grade 2 (p < 0.001) and grade 3 (p < 0.001) hallux valgus. No significant differences in these three muscle characteristics were found between grades 1, 2 and 3 (p > 0.0125).

Conclusions

We speculate that morphological changes to the abductor hallucis muscle occur early in the development of the deformity.
An exploration of student experiences of using biology podcasts in nursing training
Authors: Mostyn Alison , Jenkinson Claire M , McCormick Damion , Meade Oonagh , Lymn Joanne S
Published: January 2013

Background

Students regard biological science as one of the most difficult components of the nursing curriculum. However, a good understanding of this area is essential for effective nursing practice. The aim of this study was to explore nursing students’ perceptions of the usefulness of supplementary biology podcasts for their learning.

Methods

Biological science podcasts (n = 9) were made available to first-year nursing students (n = 189) as supplementary learning tools. On completion of their first year, students were asked to complete a survey which investigated the frequency of their podcast use, reasons for use and their perception of the usefulness of podcasts as a learning tool. 153 of these students participated in the survey study (80.9%). Two focus groups were conducted with students (n = 6) to gain a detailed understanding of student experiences of the usefulness of the podcasts for their learning.

Results

Survey data demonstrated that most students (71%) accessed at least one podcast. The majority of students who reported accessing podcasts agreed that they were useful as learning tools (83%), revision aids (83%) and that they helped promote understanding of course materials (72%). Focus group participants discussed how they found podcasts especially useful in terms of revision. Students valued being able to repeatedly access the lecture materials, and appreciated having access to podcasts from a range of lecturers. Focus group members discussed the benefits of live recordings, in terms of valuing the information gleaned from questions asked during the lecture sessions, although there were concerns about the level of background noise in live recordings. Lack of awareness of the availability of podcasts was an issue raised by participants in both the survey component and the focus groups and this negatively impacted on podcast use.

Conclusions

Nursing students found the availability of biology podcasts helpful for their learning. Successful implementation of these tools to support learning requires teaching staff to understand and promote the importance of these tools.
Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study
Authors: Buys Antoinette V , Van Rooy Mia-Jean , Soma Prashilla , Van Papendorp Dirk , Lipinski Boguslaw , Pretorius Etheresia
Published: January 2013

Red blood cells (RBCs) are highly deformable and possess a robust membrane that can withstand shear force. Previous research showed that in diabetic patients, there is a changed RBC ultrastructure, where these cells are elongated and twist around spontaneously formed fibrin fibers. These changes may impact erythrocyte function. Ultrastructural analysis of RBCs in inflammatory and degenerative diseases can no longer be ignored and should form a fundamental research tool in clinical studies. Consequently, we investigated the membrane roughness and ultrastructural changes in type 2 diabetes. Atomic force microscopy (AFM) was used to study membrane roughness and we correlate this with scanning electron microscopy (SEM) to compare results of both the techniques with the RBCs of healthy individuals. We show that the combined AFM and SEM analyses of RBCs give valuable information about the disease status of patients with diabetes. Effectiveness of treatment regimes on the integrity, cell shape and roughness of RBCs may be tracked, as this cell’s health status is crucial to the overall wellness of the diabetic patient.
Fibronectin coating of oxygenator membranes enhances endothelial cell attachment
Authors: Cornelissen Christian G , Dietrich Maren , Gromann Kai , Frese Julia , Krueger Stefan , Sachweh Jörg S , Jockenhoevel Stefan
Published: January 2013

Background

Extracorporeal membrane oxygenation (ECMO) can replace the lungs’ gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. As a first step towards this aim, we hypothesized that coating the oxygenator’s gas exchange membrane with proteins might positively influence the attachment and proliferation of arterial endothelial cells.

Methods

Sheets of polypropylene (PP), polyoxymethylpentene (TPX) and polydimethylsiloxane (PDMS), typical material used for oxygenator gas exchange membranes, were coated with collagen, fibrinogen, gelatin or fibronectin. Tissue culture treated well plates served as controls. Endothelial cell attachment and proliferation were analyzed for a period of 4 days by microscopic examination and computer assisted cell counting.

Results

Endothelial cell seeding efficiency is within range of tissue culture treated controls for fibronectin treated surfaces only. Uncoated membranes as well as all other coatings lead to lower cell attachment. A confluent endothelial cell layer develops on fibronectin coated PDMS and the control surface only.

Conclusions

Fibronectin increases endothelial cells’ seeding efficiency on different oxygenator membrane material. PDMS coated with fibronectin shows sustained cell attachment for a period of four days in static culture conditions.
The effects of deprivation and relative deprivation on self-reported morbidity in England: an area-level ecological study
Authors: Zhang Xin , Cook Penny A , Lisboa Paulo J , Jarman Ian H , Bellis Mark A
Published: January 2013

Background

Socioeconomic status gradients in health outcomes are well recognised and may operate in part through the psychological effect of observing disparities in affluence. At an area-level, we explored whether the deprivation differential between neighbouring areas influenced self-reported morbidity over and above the known effect of the deprivation of the area itself.

Methods

Deprivation differentials between small areas (population size approximately 1,500) and their immediate neighbours were derived (from the Index of Multiple Deprivation (IMD)) for Lower Super Output Area (LSOA) in the whole of England (n=32482). Outcome variables were self-reported from the 2001 UK Census: the proportion of the population suffering Limiting Long-Term Illness (LLTI) and ‘not good health’. Linear regression was used to identify the effect of the deprivation differential on morbidity in different segments of the population, controlling for the absolute deprivation. The population was segmented using IMD tertiles and P2 People and Places geodemographic classification. P2 is a commercial market segmentation tool, which classifies small areas according to the characteristics of the population. The classifications range in deprivation, with the most affluent type being ‘Mature Oaks’ and the least being ‘Urban Challenge’.

Results

Areas that were deprived compared to their immediate neighbours suffered higher rates of ‘not good health’ (β=0.312, p<0.001) and LLTI (β=0.278, p<0.001), after controlling for the deprivation of the area itself (‘not good health’—ß=0.655, p<0.001; LLTI—ß=0.548, p<0.001). The effect of the deprivation differential relative to the effect of deprivation was strongest in least deprived segments (e.g., for ‘not good health’, P2 segments ‘Mature Oaks’—β=0.638; ‘Rooted Households’—β=0.555).

Conclusions

Living in an area that is surrounded by areas of greater affluence has a negative impact on health in England. A possible explanation for this phenomenon is that negative social comparisons between areas cause ill-health. This ‘psychosocial effect’ is greater still in least deprived segments of the population, supporting the notion that psychosocial effects become more important when material (absolute) deprivation is less relevant.
High efficacy of CpG-ODN, Cetuximab and Cisplatin combination for very advanced ovarian xenograft tumors
Authors: Sommariva Michele , de Cesare Michelandrea , Meini Alessandra , Cataldo Alessandra , Zaffaroni Nadia , Tagliabue Elda , Balsari Andrea
Published: January 2013

Background

To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune responses, in combination with other possible therapeutic reagents in ovarian carcinoma ascites-bearing athymic mice.

Methods

Mice injected i.p. with IGROV-1 ovarian cancer cells were treated at different stages of ascites progression for 4 weeks with CpG-ODN, alone or in combination with Bevacizumab, Polyinosinic:Polycytidylic acid (Poly(I):Poly(C)), Gefitinib, Cetuximab and Cisplatin. Median survival time (MST) was calculated for each group. IGROV-1 cells treated or not with Cetuximab were assayed for antibody-dependent cellular cytotoxicity by 51Cr-release assay, and for macrophage antibody-dependent cell-mediated phagocytosis by flow cytometry.

Results

In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I):Poly(C) or Gefitinib did not significantly increase MST as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008), with 4/8 mice alive at the end of the experiment. In experiments in mice showing increased abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection), treatment with Cisplatin in addition to CpG-ODN/Cetuximab led to significantly increased MST (105.5 days; P = 0.001), with all mice still alive at 85 days, over that using CpG-ODN/Cetuximab (66 days), Cetuximab/Cisplatin (18.5 days), Cisplatin (23 days) or saline (16 days). At a very advanced stage of disease (body weight: 31.4 ± 0.9 g), when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089) vs controls.

Conclusions

CpG-ODN combination therapies that enhance the immune response in the tumor microenvironment and concomitantly target tumor cells are highly efficacious even in experimental advanced malignancies. Although differences in the distribution of TLR9 in mice and humans and the enrichment of this receptor on innate immune cells of athymic mice must be considered, our results indicate a promising strategy to treat ovarian cancer patients with bulky ascites.