bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer
Authors: Vermeij Renee , Daemen Toos , de Bock Geertruida H. , de Graeff Pauline , Leffers Ninke , Lambeck Annechien , ten Hoor Klaske A. , Hollema Harry , van der Zee Ate G. J. , Nijman Hans W.
Published: September 2010

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY‐ESO‐1 was observed in 120 (48.0%), 173 (68.9%), 208 (90.0%), 129 (56.3%), and 27 (11.0%) of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (over)expressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (over)expression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.
Relationship between Radiation Exposure and Risk of Second Primary Cancers among Atomic Bomb Survivors
Authors: Li Christopher I. , Nishi Nobuo , McDougall Jean A. , Semmens Erin O. , Sugiyama Hiromi , Soda Midori , Sakata Ritsu , Hayashi Mikiko , Kasagi Fumiyoshi , Suyama Akihiko , Mabuchi Kiyohiko , Davis Scott , Kodama Kazunori , Kopecky Kenneth J.
Published: September 2010

Radiation exposure is related to risk of numerous types of cancer, but relatively little is known about its effect on risk of multiple primary cancers. Using follow-up data through 2002 from 77,752 Japanese atomic bomb survivors, we identified 14,048 participants diagnosed with a first primary cancer, of whom 1,088 were diagnosed with a second primary cancer. Relationships between radiation exposure and risks of first and second primary cancers were quantified using Poisson regression. There was a similar linear dose-response relationship between radiation exposure and risks of both first and second primary solid tumors [excess relative risk (ERR)/Gy = 0.65; 95% confidence interval (CI), 0.57–0.74 and ERR/Gy = 0.56; 95% CI, 0.33–0.80, respectively] and risk of both first and second primary leukemias (ERR/Gy = 2.65; 95% CI, 1.78–3.78 and ERR/Gy = 3.65; 95% CI, 0.96–10.70, respectively). Background incidence rates were higher for second solid cancers, compared with first solid cancers, until about age 70 years for men and 80 years for women (P < 0.0001), but radiation-related ERRs did not differ between first and second primary solid cancers (P = 0.70). Radiation dose was most strongly related to risk of solid tumors that are radiation-sensitive including second primary lung, colon, female breast, thyroid, and bladder cancers. Radiation exposure confers equally high relative risks of second primary cancers as first primary cancers. Radiation is a potent carcinogen and those with substantial exposures who are diagnosed with a first primary cancer should be carefully screened for second primary cancers, particularly for cancers that are radiation-sensitive. Cancer Res; 70(18); 7187–98. ©2010 AACR.
Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling
Authors: Milosavljevic Nina , Duranton Christophe , Djerbi Nadir , Puech Pierre Henri , Gounon Pierre , Lagadic-Gossmann Dominique , Dimanche-Boitrel Marie Thérèse , Rauch Cyril , Tauc Michel , Counillon Laurent , Poët Mallorie
Published: September 2010

Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range of short-term side effects that are unlikely to be related to its genomic action. As cisplatin has been shown to modify membrane properties in different cell systems, we investigated its effects on mechanosensitive ion transporters and channels. We show here that cisplatin is a noncompetitive inhibitor of the mechanosensitive Na+/H+ exchanger NHE-1, with a half-inhibition concentration of 30 μg/mL associated with a decrease in Vmax and Hill coefficient. We also showed that it blocks the Cl− and K+ mechanosensitive channels VSORC and TREK-1 at similar concentrations. In contrast, the nonmechanosensitive Cl− and K+ channels CFTR and TASK-1 and the Na+-coupled glucose transport, which share functional features with VSORC, TREK-1, and NHE-1, respectively, were insensitive to cisplatin. We next investigated whether cisplatin action was due to a direct effect on membrane or to cortical actin remodeling that would affect mechanosensors. Using scanning electron microscopy, in vivo actin labeling, and atomic force microscopy, we did not observe any modification of the Young's modulus and actin cytoskeleton for up to 60 and 120 μg/mL cisplatin, whereas these concentrations modified membrane morphology. Our results reveal a novel mechanism for cisplatin, which affects mechanosensitive channels and transporters involved in cell fate programs and/or expressed in mechanosensitive organs in which cisplatin elicits strong secondary effects, such as the inner ear or the peripheral nervous system. These results might constitute a common denominator to previously unrelated effects of this drug. Cancer Res; 70(19); 7514–22. ©2010 AACR.
A 28-Amino-Acid Peptide Fragment of the Cupredoxin Azurin Prevents Carcinogen-Induced Mouse Mammary Lesions
Authors: Mehta Rajeshwari R. , Hawthorne Michael , Peng Xinjian , Shilkaitis Ann , Mehta Rajendra G. , Beattie Craig W. , Das Gupta Tapas K.
Published: September 2010

Azurin, a member of the cupredoxin family of redox proteins, preferentially penetrates human cancer cells and exerts cytostatic and apoptotic effects. Azurin and amino acids 50-77 (p28) of azurin also produce a dose-dependent reduction in the proliferation of human mammary cancer by increasing the level of the tumor suppressor protein p53 in the cancer cell nucleus. We show that the development of 7,12-dimethylbenz[a]anthracene–induced hormone-dependent premalignant mammary ductal lesions and hormone-independent mammary alveolar lesions in mouse mammary gland organ culture is also significantly reduced by azurin and p28. The dose-dependent reduction in carcinogen-induced mammary cell proliferation by p28 was associated with an increase in the expression of p53. p28 also enhanced the inhibitory effect of a low dose of the antiestrogen tamoxifen on the development of hormone-dependent mammary ductal lesions, but did not enhance the inhibitory activity of fenretinide (N-4-hydroxyphenyl retinamide) on hormone-independent mammary alveolar lesions. These observations suggest that cupredoxins and fragments derived from them can exert a chemopreventive effect on carcinogen-induced mammary gland transformation, irrespective of hormonal environment, and enhance the inhibitory effects of tamoxifen in this model of preneoplastic mammary development. Cancer Prev Res; 3(10); 1351–60. ©2010 AACR.
Relationship of Intracranial Pressure and Cerebral Perfusion Pressure with Outcome in Young Children after Severe Traumatic Brain Injury
Authors: Mehta Amit , Kochanek Patrick M. , Tyler-Kabara Elizabeth , Adelson P. David , Wisniewski Stephen R. , Berger Rachel P. , Sidoni Maria D. , Bell Rachelle L. , Clark Robert S.B. , Bell Michael J.
Published: September 2010

Traumatic brain injury (TBI) is the most common cause of death for children less than 18 years of age. Current standards of care for children with severe TBI include monitoring of intracranial pressure (ICP), and goal-directed therapies to minimize ICP and optimize cerebral perfusion pressure (CPP; the mathematical difference between the mean arterial pressure and ICP). Current guidelines for ICP and CPP thresholds suggest that age-based thresholds should be adopted, but few studies have included the youngest children affected by TBI (those <2 years of age). We performed a retrospective analysis of our pediatric neurotrauma database to determine if ICP and CPP thresholds associated with favorable neurological outcome could be determined, or if the number of episodic alterations in the parameters (ICP >15 or >20 mm Hg; CPP <40 mm Hg, <45 mm Hg or <50 mm Hg) was different between children with favorable and unfavorable outcomes (based on dichotomous Glasgow Outcome Scale score at 6 months after TBI). Data from 22 children (of whom 81% had suffered from inflicted childhood neurotrauma) were analyzed in the first 7 days. Children with unfavorable outcome had more hourly readings of CPP of <45 mm Hg compared to children with favorable outcome [median (25–75%): 2 (1–31) vs. 0 (0–2); p <0.05]. There was no difference between the number of hourly readings of ICP of >20 mm Hg between the outcome groups [median (25–75%): favorable 0 (0–1) vs. unfavorable 1 (0–4); p = 0.17]. To our knowledge, this is the first exploratory report to test if CPP and ICP thresholds can be established for this young population of children after TBI, and it suggests a CPP target threshold of 45 mm Hg. Despite good ICP control in this population, there was still a 50% incidence of unfavorable outcome, suggesting that there may be unique physiologic parameters that need to be targeted in infants with severe TBI. A prospective study is needed to fully determine what goals should be targeted for this vulnerable population.
Age Is a Determinant of Leukocyte Infiltration and Loss of Cortical Volume after Traumatic Brain Injury
Authors: Claus Catherine P. , Tsuru-Aoyagi Kyoko , Adwanikar Hita , Walker Breset , Whetstone William , Noble-Haeusslein Linda J.
Published: September 2010

There is increasing evidence that the inflammatory response differs in the injured developing brain as compared to the adult brain. Here we compared cerebral blood flow and profiled the inflammatory response in mice that had been subjected to traumatic brain injury (TBI) at postnatal day (P)21 or at adulthood. Relative blood flow, determined by laser Doppler, revealed a 30% decrease in flow immediately after injury followed by prominent hyperemia between 7 and 35 days after injury in both age groups. The animals were euthanized at 1–35 days after injury and the brains prepared for the immunolocalization and quantification of CD45-, GR-1-, CD4- and CD8-positive (+) cells. On average, the number of CD45+ leukocytes in the cortex was significantly higher in the P21 as compared to the adult group. A similar trend was seen for GR-1+ granulocytes, whereas no age-related differences were noted for CD4+ and CD8+ cells. While CD45+ and GR-1+ cells in the P21 group remained elevated, relative to shams, over the first 2 weeks after injury, the adult group showed a time course limited to the first 3 days after injury. The loss of ipsilateral cortical volumes at 2 weeks after injury was significantly greater in the adult relative to the P21 group. While the adult group showed no further change in cortical volumes, there was a significant loss of cortical volumes between 2 and 5 weeks after injury in the P21 group, reaching values similar to that of the adult group by 5 weeks after injury. Together, these findings demonstrate age-dependent temporal patterns of leukocyte infiltration and loss of cortical volume after TBI.
Soil nematode community changes associated with compost amendments
Authors: Renčo Marek , Sasanelli Nicola , D'Addabbo Trifone , Papajová Ingrid
Published: September 2010

Five composts (C1: fresh olive pomace, straw, chicken manure, urea; C2: fresh olive pomace, lettuce residues, cow manure, straw, sawdust; C3: sewage sludge, municipal green residues; C4: grass, leaves, tree branches, soil; C5: by-product from penicillin production (mycelium), straw and sawdust) were tested in a pot experiment to investigate their short-term effect on the nematode community of a grassland soil. Composts were mixed with soil at the rates of 10, 25, 50 and 100 g (kg soil)–1 and barley was sown in each potting mixture after a 2-month decomposition period. Nematodes were extracted from each pot 5 months after barley sowing, identified at genus level and grouped into bacterial, fungal and root fungal feeders, predators, omnivores and plant parasites. Bacterial feeders, predators and omnivores were favoured by amendments with composted penicillin substrate and partly by compost from olive pomace, whereas composts from green wastes and sewage sludge suppressed these trophic groups except for predators. All compost treatments suppressed fungal feeders as well as significantly reducing the density of plant-parasitic nematodes compared with non-amended soil. The highest suppressiveness on plant-parasitic nematodes was found for the composts from urban green residues, penicillin substrate and olive pomace plus cow manure. Suppressive effect was hypothesised to be related to ammoniacal nitrogen content of the composts. Composts from fungal mycelium or olive pomace seem to be the most suitable for application in nematode management strategies due to their low impact on beneficial trophic groups.
A health website recommendation from Gold Coast general practitioners to their patients
Authors: Usher Wayne
Published: September 2010

Introduction: To identify health website recommendation trends by Gold Coast (Australia) general practitioners (GPs) to their patients.

Method: A mixed method approach to data collection and analysis was employed. Quantitative data were collected using a prepaid postal survey, consisting of 17 questions, mailed to 250 (61 per cent) of 410 GPs on the Gold Coast (Australia). The resulting empirical data and resulting themes were further used to design semi-structured interview questions. A total of 15 (8 male, 7 female) GPs volunteered to be interviewed.

Results: Fifty-nine per cent of participating GPs recommend health websites to their patients during consultations. Male GPs (63 per cent), those aged 41–50 years (55 per cent), and those practising for < 10 years (60 per cent) were more inclined to recommend a health website to a patient. From the survey data, eight principle categories presented themselves as to GPs’ recommendation trends, these including; ‘Do not recommend websites’ – (1) Limited time, (2) Prefer to personally discuss, (3) Reliability issues, (4) Biased information – and ‘Do recommend health websites’ – (5) Helps to educate patient, (6) Enhances the doctor–patient relationship, (7) Age-appropriate technology, (8) Treatment orientated. The semi-structured interviews presented a further eight sub-categories and have been identified as: (1) Fewer female GPs than male GPs recommend health websites, (2) Age and years of experience of GPs affect internet prescription trends, (3) Patients more knowledgeable, (4) ‘Sweeteners’ offered by pharmaceutical companies, (5) A high influence by pharmaceutical companies on the WWW/internet, (6) A lack of knowledge pertaining to reliability issues – issues of trust, (7) Limited knowledge pertaining to interactivity and usability components, and (8) A need for further medical education for GPs.

Conclusion: More than half of the surveyed GPs actively recommend websites to their patients, with a GP’s sex, age and years of experience influencing his or her recommendation decisions. There are numerous and varied reasons as to why GPs ‘do’ or ‘do not’ recommend health websites to their patients. Web-based continuing medical education courses or programmes in medical schools may help GPs develop the skills necessary for the delivery of effective e-health care.
Comparison Focus in Intergroup Comparisons: Who We Compare to Whom Influences Who We See as Powerful and Agentic
Authors: Bruckmüller Susanne , Abele Andrea E.
Published: September 2010

In intergroup comparisons one group usually becomes the implicit norm that other groups are compared to. Three studies address the consequences that the direction of the comparison has for perceptions of the compared groups. For real groups (Experiment 1) and fictitious groups (Experiments 2 and 3) participants perceived a group as more powerful and higher in status when it had been the norm rather than the effect to be explained in a text comparing two groups. Moreover, norm groups and their “typical” members were perceived as more agentic and less communal than comparison groups, and these attributions were mediated by the ascription of power. The authors conclude that systematic ways of explaining one group rather than another could serve as a subtle tool to perpetuate the status quo of intergroup power relations.
In Search of Eminence: A Personal Brand-Building Perspective on the Achievement of Scholarly Prominence in Marketing
Authors: Noble Charles H. , Bentley John P. , Campbell David , Singh Jatinder J.
Published: September 2010

In marketing, as in many other academic disciplines, new scholars are often taught a simple formula for the achievement of professional success: the single-minded pursuit of “A”-level journal publications. Although the goal of producing high-quality research that is ultimately published in top level journals is certainly worthwhile, the attainment of true prominence or “eminence” in the discipline may draw on a more complex formula. Anecdotal evidence suggests that the most prolific scholars may not always be the most eminent. Taking a personal brand-building perspective, this study examines a wide range of factors that may influence the attainment of scholarly eminence in the marketing discipline. Using a sample of 297 marketing academicians, this study finds that although a raw volume of publications influences eminence, publishing top-tier publications is even more significant. Perhaps most interestingly, this work highlights several different professional paths that can lead to scholarly eminence, including a tradeoff between publishing sole-authored pieces and “A”-level volume, and the eminence-enhancing effects of various professional activities. These findings suggest that a single-minded model of the path to scholarly eminence is supported but not necessarily complete.
Development of an Infrequency Index for the CAARS
Authors: Suhr Julie A. , Buelow Melissa , Riddle Tara
Published: September 2010

There is a clinical need for measurement of noncredible self-reporting of symptoms of attention deficit hyperactivity disorder (ADHD) in adults presenting for ADHD evaluation. The present study describes the development of initial validity data for an Infrequency Index for the Conner’s Adult Attention Deficit/Hyperactivity Rating Scale (CII). Items for the CII were obtained from a large sample of nontreatment seeking university students, including individuals with a self-reported history of ADHD diagnosis. Items endorsed infrequently in the sample, including those with ADHD diagnoses, were identified and summed to create the CII. Initial validation data were gathered from a sample of individuals seeking clinical evaluation for ADHD. The CII was strongly related to noncredibly high symptom report and was also related to noncredible performance on cognitive measures. Results provide initial support for the CII’s use in assessing noncredible overreporting on the Conner’s Adult Attention-Deficit/Hyperactivity Rating Scale.
ASKing the Kids: How Children View Their Abilities After Perinatal Stroke
Authors: Barkat-Masih Monica , Saha Chandan , Golomb Meredith R.
Published: September 2010

A total of 19 children with a history of perinatal stroke were asked how they saw their own motor abilities and disabilities using the Activities Scale for Kids (ASK) performance and capability questionnaires. The median ASK performance score was significantly lower (86.7) than the median ASK capability score (93.4; P = .03), suggesting children felt they were not doing everything they were capable of doing. Performance and capability total scores were not associated with gender or stroke type; lower performance and capability scores were associated with cerebral palsy. Within groups, performance scores were significantly lower than capability scores in girls (P = .02), children with presumed perinatal stroke (P = .02), children with unilateral stroke (P = .02), and children with large versus small branch unilateral middle cerebral artery stroke (P = .03). Further work is needed to understand why these children’s performance does not match perceived capability.
Voices of Convergence or Conflict? A Path Analysis Investigation of Selective Exposure to Political Websites
Authors: Johnson Thomas J. , Zhang Weiwu , Bichard Shannon L.
Published: September 2010

This research used a path analysis model to explore the degree to which reliance on off-line and online media, off-line and online discussion of political issues, as well as political attitudes predict whether an individual will engage in selective exposure to political websites. The study also looked at selective avoidance of contradictory information on websites. The results indicate that respondents did indeed practice selective exposure when accessing information on political websites, especially among those who are politically active online and those who rely heavily on websites and blogs for political information. However, the results showed that selective avoidance did not occur, with those exhibiting increased political interest and online participation significantly less likely to avoid information that challenges their views.
Review of Chronic Graft-Versus-Host Disease in Children After Allogeneic Stem Cell Transplantation
Authors: Liu Ying-Mei , Hockenberry Marilyn
Published: September 2010

This review presents a summary of the research literature related to the incidence and risk factors for chronic graft-versus-host disease in children following allogeneic hematopoietic stem cell transplantation. The range of incidence of chronic graft-versus-host disease in children found in this review was large, from 0% to 46%. Incidence of chronic graft-versus-host disease was influenced by sample size, time posttransplantation, and stem cell source. Characteristics of the person (eg, child’s age and gender) and disease/treatment (eg, sources of transplant) are associated with chronic graft-versus-host disease in children after stem cell transplantation. Person and disease/treatment characteristics provide a framework for understanding the factors associated with chronic graft-versus-host disease symptom experiences in children after stem cell transplantation. Timely assessment of presenting chronic graft-versus-host disease symptoms is critical for treatment and prognosis. Nursing interventions should focus on educating children and parents about the signs and symptoms of chronic graft-versus-host disease. The summary of supportive nursing care for children with chronic graft-versus-host disease provides important information to tailor effective management strategies for children with chronic graft-versus-host disease.
A Latent Class Analysis of Depressive and Externalizing Symptoms in Nonreferred Adolescents
Authors: Mezulis Amy , Stoep Ann Vander , Stone Andrea L. , McCauley Elizabeth
Published: September 2010

Both depressive and externalizing symptoms are common in adolescence and often co-occur. The purpose of this study was to examine whether adolescents’ patterns of depressive and externalizing symptoms can be differentiated into discrete classes and whether these classes are best distinguished by the number or type of symptoms. We examined whether there are naturally occurring discrete classes of adolescents characterized by depressive symptoms only, externalizing symptoms only, or co-occurring depressive and externalizing symptoms. In this study, 2,187 nonreferred, public school sixth graders self-reported depressive and externalizing symptoms, and these symptoms were analyzed with latent class analysis. Six latent classes of depressive and externalizing symptoms were identified; classes differed primarily by the number, not type, of symptoms endorsed. Youth with elevations in one symptom type were likely to have elevations in the other symptom type. Approximately 5% of adolescents displayed clinically significant elevations in both depressive and externalizing symptoms. Implications for understanding the co-occurrence of depressive and externalizing symptoms in adolescence are discussed.
Madame Curie above the fold: Divergent perspectives on Curie’s visit to the United States in the American press
Authors: Owens Trevor
Published: September 2010

On May 11, 1921, the world’s most famous female scientist, Marie Curie, began a 10-week tour of the United States. Curie’s biographers have argued that instead of portraying Curie as a scientist, the American press’ emphasis on Curie’s role as a mother, widow, and healer created a mythic Curie with traditional female virtues that served to make this unconventional woman less threatening to traditional values. This article complicates that approach by considering coverage outside the daily press, such as magazines, which emphasized Curie’s accomplishments as a scientist. Tracing the development of Curie’s story in the press, the article offers insight into the way coverage of Curie’s trip both shaped and was shaped by notions of women’s place in science and American society.
The Influence of Presumed Media Influence on News About Science and Scientists
Authors: Tsfati Yariv , Cohen Jonathan , Gunther Albert C.
Published: September 2010

According to the authors, much of media coverage of science and scientists is explained by scientists’ beliefs regarding the impact of appearing in media on their careers. Their argument rests on recent advances in communication theory, stressing “the influence of presumed media influence,” and contributes to our understanding of why some scientists receive more media coverage than others. Combined data from a survey of scholars in an Israeli research university ( n = 166) and content analysis data on the frequency of the scholars’ appearances in the media were used to test this argument. Structural equation modeling revealed that the scholars’ belief in the influence of media increased their motivation and efforts to obtain media coverage, which in turn was related to the number of their actual media appearances.
Fighting Crime by Fighting Misconceptions and Blind Spots in Policy Theories: An Evidence-Based Evaluation of Interventions and Assumed Causal Mechanisms
Authors: van Noije Lonneke , Wittebrood Karin
Published: September 2010

How effective are policy interventions to fight crime and how valid is the policy theory that underlies them? This is the twofold research question addressed in this article, which presents an evidence-based evaluation of Dutch social safety policy. By bridging the gap between actual effects and assumed effects, this study seeks to make fuller use of the practical relevance of evidence-based evaluations. The results reveal promising interventions and mechanisms for policy practice. In addition, the chosen approach advances current practice using evidence-based outcomes to distinguish plausible from implausible policy assumptions. An urgent need is signaled for governments to provide substantive reasoning for their policy choices. Many of the assumptions that correspond with evidence from impact evaluations relate to general prevention, often found within the strategy of situational prevention. Contrary to any general preventive or short-term effects, the assumptions regarding long-term specific prevention through law enforcement cannot be taken as read.
The California Coalinga Chrysotile Miners and Millers - Further Evidence for a Lack of Attributable Disease
Authors: Ilgren E.B.
Published: September 2010

The health risks to humans from exposure to ‘‘pure’’ short-fibre chrysotile, the most common form of asbestos, have been the subject of considerable debate. Identification of three cohorts of miners and millers exposed to amphibole-free short-fibre chrysotile has enabled this issue to be addressed. The findings detailed in this report strongly suggest that none of the exposed workers, or others exposed para-occupationally or environmentally to the same form of asbestos, display any asbestos-related disease.
A home away from home: The meaning of home according to families of residents with dementia
Authors: Robinson Carole A. , Colin Reid R. , Cooke Heather A.
Published: September 2010

This study sought to understand the ways in which family caregivers to institutionalized relatives with dementia perceived and experienced the relocation of their relative to a more home-like setting of care. Twenty-nine family members were interviewed through focus groups and individual interviews following the closing of two traditional care facilities and the subsequent migration of all residents to dementia cottages. Questions focused on the assessment and evaluation of quality of care. Results of this qualitative study pointed to the centrality of relationships in creating a truly homelike environment, in addition to what constitutes effective relational practice from the family perspective. We argue that the creation of a meaningful home for persons with dementia must encompass a relational orientation, both philosophically and in practice, that is inclusive of resident, staff, and family.
The Influence of Diabetes on Degree of Abdominal Aortic Aneurysm Tissue Inflammation
Authors: Arapoglou Vassilis , Kondi-Pafiti Agathi , Rizos Demetrios , Carvounis Eleni , Frangou-Plemenou Matrona , Kotsis Thomas , Katsenis Konstantinos
Published: September 2010

Abdominal aortic aneurysm (AAA) progression and disease resistance are related to transmural degenerative processes and an inflammatory infiltration (INF). Diabetes is associated with low prevalence and growth rate of AAA. We sought to characterize INF in established AAA (INFAAA), in diabetic patients. From 89 male patients aged 52 to 83 years, aneurysm specimens obtained at open asymptomatic nonruptured AAA repair were graded for INF and immunostained using antibodies against T-lymphocytes (CD3) and macrophages (CD68). Diabetic patients had an odds ratio (OR) 3.8, 95% confidence interval ([CI] 1.14-12.96), P = .03, of experiencing above-median INFAAA. These associations were affected by serum glucose (SG) levels (OR 3.6, 95% CI [0.72-18.77]; P = .1). Macrophage subpopulations higher in diabetic patients (1.44 ± 0.78 versus 0.98 ± 0.76; P = .02) were correlated with SG (r = .21, P = .044). Abdominal aortic aneurysms in diabetic patients are associated with higher INF. Macrophage densities are correlated with SG.
Endovascular Treatment for Chronic Arteriovenous Fistula Between Renal Artery and Inferior Vena Cava: Image in Vascular Surgery
Authors: Wolosker N. , Oba CM , Espirito Santo FRF , Puech-Leao P.
Published: September 2010

Arteriovenous fistula involving renal artery and inferior vena cava are rare. We report the case of a 47-year-old woman with a chronic arteriovenous fistula between right renal artery and inferior vena cava due to a penetrating trauma. Another finding was a vena cava aneurysm caused by the fistula. The patient was successfully treated with a covered stent in the renal artery. Diagnosis and postoperative control have been documented with CT scan. Endovascular techniques may be effective and minimally invasive option for treatment and renal preservation in renal-cava arteriovenous fistulae.
Hierarchical structure and fractal dimensions of tendon
Authors: Liu J.-F. , He J.-H.
Published: September 2010

A tendon shows excellent advantages in transmitting large loads efficiently and also in storing elastic energy during locomotion possibly due to its hierarchical structure. Its fractal dimension is calculated, which is quite close to the golden mean, 1·618. The present study might provide a new interpretation for the reason why the tendon has so many excellent properties. Based on this theory, a composite yarn with hierarchical structure is designed.
Surface modification of EPDM rubber by microwave excited plasmas
Authors: Oliveira M. S. , Mello S. A. C. , da Silva Sobrinho A. S. , Grigorov K. G. , Massi M. , Maciel H. S. , Dutra J. C. N.
Published: September 2010

In the present work, a microwave excited plasma (2·45 GHz, 1 kW) was used to modify the surface characteristics of the ethylene propylene diene monomer rubber. The samples were treated with a mixture of nitrogen, hydrogen and argon plasmas. The operating gas pressure was in the 0·2–1 Torr range, the gas flowrate between 5 and 100 sccm and the treatment time varied from 10 to 600 s. The influence of the plasma treatment on the superficial characteristics of the samples was analysed by contact angle measurements and atomic force microscopy. The results show that the plasma treatment can promote an important decrease in the contact angle from 101° for untreated sample to 34° for samples treated in a mixture of H2/N2/Ar for 2 min, which corresponds an increase on the rubber surface adhesion work from 59 to 133 mJ m−2.
A mechanistic rationale for combining alemtuzumab and rituximab in the treatment of ALL
Authors: Nijmeijer Bart A. , van Schie Marianke L. J. , Halkes Constantijn J. M. , Griffioen Marieke , Willemze Roelof , Falkenburg J. H. Frederik
Published: September 2010

B-lineage acute lymphoblastic leukemia (ALL) may express CD52 and CD20. Alemtuzumab (ALM) and rituximab (RTX) are therapeutic antibodies directed against CD52 and CD20, respectively, but showed limited activity against ALL in clinical trials. The mechanisms for the impaired responses remained unclear. We studied expression of CD52 and CD20 on ALL cells and found that most cases coexpressed CD52 and CD20. However, distinct CD52-negative (CD52−) subpopulations were detected in most cases as the result of defective glycophosphatidyl-inositol anchoring. Although ALM efficiently eradicated CD52-positive (CD52+) cells in NOD/scid mice engrafted with primary human ALL, CD52− subclones escaped therapy. In the same model, RTX showed limited activity resulting from occurrence of CD20 down-modulation. However, CD52− cells concurrently lacked the glycophosphatidyl-inositol–anchored complement regulators CD55 and CD59 and showed increased susceptibility to RTX-mediated complement-dependent cytotoxicity in vitro. At the same time, ALM was shown to inhibit down-modulation of CD20 in response to RTX by depleting the trogocytic capacity of phagocytic cells. Probably because of these complementary mechanisms, combined administration of ALM and RTX induced complete responses in vivo. Based on these data, we propose a mechanistic rationale for combined application of RTX and ALM in ALL.
Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations
Authors: Pecci Alessandro , Gresele Paolo , Klersy Catherine , Savoia Anna , Noris Patrizia , Fierro Tiziana , Bozzi Valeria , Mezzasoma Anna Maria , Melazzini Federica , Balduini Carlo L.
Published: September 2010

Platelet transfusion is currently the primary medical treatment for reducing thrombocytopenia in patients with inherited thrombocytopenias. To evaluate whether stimulating megakaryopoiesis could increase platelet count in these conditions, we treated patients with a severe thrombocytopenia induced by MYH9 mutations (MYH9-related disease) with a nonpeptide thrombopoietin receptor agonist, eltrombopag. Twelve adult patients with MYH9-RD and platelet counts of less than 50 × 109/L received 50 mg of eltrombopag orally per day for 3 weeks. Patients who achieved a platelet count higher than 150 × 109/L stopped therapy, those with 100 to 150 platelets × 109/L continued treatment at the same eltrombopag dose for 3 additional weeks, while those with less than 100 platelets × 109/L increased the eltrombopag dose to 75 mg for 3 weeks. Major responses (platelet count of at least 100 × 109/L or 3 times the baseline value) were obtained in 8 patients, minor responses (platelet counts at least twice the baseline value) in 3. One patient did not respond. Bleeding tendency disappeared in 8 of 10 patients with bleeding symptoms at baseline. Mild adverse events were reported in 2 patients. The availability of thrombopoietin mimetics opened new prospects in the treatment of inherited thrombocytopenias. This study is registered at www.clinicaltrials.gov as NCT01133860 (European Union Drug Regulating Authorities Clinical Trials number 2008-001903-42).
Obtaining additional information by using exercise testing in the laboratory in the diagnosis of asthma
Authors: Stensrud T.
Published: September 2010

Educational aims

To explain how to get more information out of an exercise challenge.

To obtain knowledge about different exercise test protocols and ergometers.

To obtain knowledge about the importance of assessing different physiological variables during exercise.

To obtain knowledge about how different climatic conditions influence exercise-induced bronchoconstriction (EIB) and exercise capacity.

Different test protocols are commonly used in the diagnosis of EIB and in the assessment of exercise capacity (). Recently one study has shown the possibility of combining assessment of EIB and into one EIB test protocol, even though the gold standard in assessment of is an incremental protocol. Additional and useful information about asthma can be obtained and differential diagnoses to EIB can be assessed by measuring different physiological variables during the EIB challenge. The following article will focus on the advantages of measuring exercise capacity during an EIB test, after a short discussion of different test protocols and ergometers.
Alternatives to exercise challenge for the objective assessment of exercise-induced bronchospasm: eucapnic voluntary hyperpnoea and the osmotic challenge tests
Authors: Porsbjerg C. , Brannan J.D.
Published: September 2010

Educational aims

To describe alternative tests for the assessment of exercise-induced bronchoconstriction and to describe the mechanisms by which bronchoconstriction is caused.

To describe how these tests are performed and how to interpret the test results.

To choose the most appropriate test for a given clinical problem.

Exercise-induced bronchoconstriction (EIB) is caused by evaporative water loss due to conditioning large volumes of air in a short period. This leads to an increase in osmolarity of the airway surface, which provides a favourable environment for release of bronchoconstricting mediators from inflammatory cells in the airways. Thus, stimuli that mimic this water loss or increase the osmolarity of the airway surface may be used as ‘surrogates’ for exercise challenge testing. The most widely used tests are eucapnic voluntary hyperpnoea (EVH) or osmotic challenges (e.g.hyperosmolar saline and mannitol). However, there are some differences in the methodology that need to be considered when using these tests. Importantly, EVH and the osmotic challenge tests overcome some of the practical and safety limitations of performing exercise testing at high intensity. The utility of these alternative tests for assessing EIB is discussed.
Exercise and asthma: β2-agonists and the competitive athlete
Authors: Boulet L-P. , Hancox R.J. , Fitch K.D.
Published: September 2010

Educational aims

Discuss the role of inhaled β-agonists in the management of exercise-induced asthma and exercise-induced bronchoconstriction.

Review the beneficialversusuntoward effects of inhaled β-agonists on asthma, exercise-induced asthma and exercise-induced bronchoconstriction.

Report on current and past usage of these drugs by Olympic athletes.

Inhaled β-agonists effectively block exercise-induced asthma/exercise-induced bronchoconstriction (EIA/EIB). They are the treatment of choice for this condition and are used by many elite and Olympic athletes. However, regular or frequent use of inhaled β-agonists leads to an increase in the underlying severity of EIA/EIB and a reduction in their bronchoprotective and bronchodilator effects, which means that they become less effective at preventing and treating EIA/EIB. Emphasis should be placed on preventative measures and anti-inflammatory treatments such as inhaled corticosteroids in order to minimise the need for inhaled β-agonists to prevent EIA/EIB.
The WTX/AMER1 gene family: evolution, signature and function
Authors: Boutet Agnès , Comai Glenda , Schedl Andreas
Published: September 2010

Background

WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/β-catenin signaling in fish and mammals thus linking it to an essential pathway involved in normal development and cancer formation. Interestingly, WTX seems to also localize to an intranuclear component called paraspeckles. In spite of the growing interest of molecular biologists in WTX, little is known about its paralogs and its phylogenetic history.

Results

Using the amino-acid sequence of WTX/AMER1 as a tool for the assignment of orthology and paralogy, we here identify two novel proteins, AMER2 and AMER3, as "WTX" related. This Amer gene family is present in all currently available vertebrate genome sequences, but not invertebrate genomes and is characterized by six conserved blocks of sequences. The phylogenetic analysis suggests that the protoAmer gene originated early in the vertebrate lineage and was then duplicated due to whole genome duplications (WGD) giving rise to the three different Amer genes.

Conclusion

Our study represents the first phylogenetic analysis of Amer genes and reveals a new vertebrate specific gene family that is likely to have played an important role in the evolution of this subphylum. Divergent and conserved molecular functions of Wtx/Amer1, Amer2 and Amer3 are discussed.
Foodborne norovirus outbreak: the role of an asymptomatic food handler
Authors: Barrabeig Irene , Rovira Ariadna , Buesa Javier , Bartolomé Rosa , Pintó Rosa , Prellezo Hortènsia , Domínguez Àngela
Published: September 2010

Background

In July 2005 an outbreak of acute gastroenteritis occurred on a residential summer camp in the province of Barcelona (northeast of Spain). Forty-four people were affected among residents and employees. All of them had in common a meal at lunch time on 13 July (paella, round of beef and fruit). The aim of this study was to investigate a foodborne norovirus outbreak that occurred in the residential summer camp and in which the implication of a food handler was demonstrated by laboratory tests.

Methods

A retrospective cohort study was designed. Personal or telephone interview was carried out to collect demographic, clinical and microbiological data of the exposed people, as well as food consumption in the suspected lunch. Food handlers of the mentioned summer camp were interviewed.

Ten stool samples were requested from symptomatic exposed residents and the three food handlers that prepared the suspected food. Stools were tested for bacteries and noroviruses. Norovirus was detected using RT-PCR and sequence analysis.

Attack rate, relative risks (RR) and its 95% confidence intervals (CI) were calculated to assess the association between food consumption and disease.

Results

The global attack rate of the outbreak was 55%. The main symptoms were abdominal pain (90%), nausea (85%), vomiting (70%) and diarrhoea (42.5%). The disease remitted in 24-48 hours. Norovirus was detected in seven faecal samples, one of them was from an asymptomatic food handler who had not eaten the suspected food (round of beef), but cooked and served the lunch. Analysis of the two suspected foods isolated no pathogenic bacteria and detected no viruses. Molecular analysis showed that the viral strain was the same in ill patients and in the asymptomatic food handler (genotype GII.2 Melksham-like).

Conclusions

In outbreaks of foodborne disease, the search for viruses in affected patients and all food handlers, even in those that are asymptomatic, is essential. Health education of food handlers with respect to hand washing should be promoted.
Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin
Authors: Serra Ryan , Al-saidi Abdel-ghany , Angelov Nikola , Nares Salvador
Published: September 2010

Background

Phenytoin (PHT) has been reported to induce gingival (gum) overgrowth (GO) in approximately 50% of patients taking this medication. While most studies have focused on the effects of PHT on the fibroblast in the pathophysiology underlying GO, few studies have investigated the potential regulatory role of macrophages in extracellular matrix (ECM) turnover and secretion of proinflammatory mediators. The aim of this study was to evaluate the effects of PHT and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin (HPPH) on LPS-elicited MMP, TIMP, TNF-α and IL-6 levels in macrophages.

Methods

Human primary monocyte-derived macrophages (n= 6 independent donors) were pretreated with 15-50 μg/mL PHT-Na+or 15-50 μg/mL HPPH for 1 hour. Cells were then challenged with 100 ng/ml purified LPS from the periodontal pathogen,Aggregatibacter actinomycetemcomitans. Supernatants were collected after 24 hours and levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, TIMP-2, TIMP-3, TIMP-4, TNF-α and IL-6 determined by multiplex analysis or enzyme-linked immunoadsorbent assay.

Results

A dose-dependent inhibition of MMP-1, MMP-3, MMP-9, TIMP-1 but not MMP-2 was noted in culture supernatants pretreated with PHT or HPPH prior to LPS challenge. MMP-12, TIMP-2, TIMP-3 and TIMP-2 were not detected in culture supernatants. High concentrations of PHT but not HPPH, blunted LPS-induced TNF-α production although neither significantly affected IL-6 levels.

Conclusion

The ability of macrophages to mediate turnover of ECM via the production of metalloproteinases is compromised not only by PHT, but its metabolite, HPPH in a dose-dependent fashion. Further, the preferential dysregulation of macrophage-derived TNF-α but not IL-6 in response to bacterial challenge may provide an inflammatory environment facilitating collagen accumulation without the counteracting production of MMPs.
Nitric Oxide is Negatively Correlated to Pain during Acute Inflammation
Authors: Hamza May , Wang Xiao-Min , Wu Tongtong , Brahim Jaime S , Rowan Janet S , Dionne Raymond A
Published: September 2010

Background:

The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.

Results:

Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100–180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo goup but not in the ketorolac group.

Conclusion:

We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.