bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol Decreases Noise‐Induced Cyclooxygenase‐2 Expression in the Rat Cochlea
Authors: Seidman Michael D. , Tang Wenxue , Bai Venkatesh Uma , Ahmad Nadir , Jiang Hao , Media Joseph , Patel Nimisha , Rubin Cory J. , Standring Robert T.
Published: February 2013

Objective

Our previous studies have demonstrated the efficacy of resveratrol, a grape constituent noted for its antioxidant and anti‐inflammatory properties, in reducing temporary threshold shifts and decreasing cochlear hair cell damage following noise exposure. This study was designed to identify the potential protective mechanism of resveratrol by measuring its effect on cyclooxygenase‐2 (COX‐2) protein expression and reactive oxygen species (ROS) formation following noise exposure.

Study Design

Controlled animal intervention study.

Setting

Otology Laboratory, Henry Ford Health System.

Subjects and Methods

Twenty‐two healthy male Fischer 344 rats (2‐3 months old) were exposed to acoustic trauma of variable duration with or without intervention. An additional 20 healthy male rats were used to study COX‐2 expression at different time points during and following treatment of 24 hours of noise exposure. Cochlear harvest was performed at various time intervals for measurement of COX‐2 protein expression via Western blot analysis and immunostaining. Peripheral blood was also obtained for ROS analysis using flow cytometry.

Results

Acoustic trauma exposure resulted in a progressive up‐regulation of COX‐2 protein expression, commencing at 8 hours and peaking at 32 hours. Similarly, ROS production increased after noise exposure. However, treatment with resveratrol reduced noise‐induced COX‐2 expression as well as ROS formation in the blood as compared with the controls.

Conclusion

COX‐2 levels are induced dramatically following noise exposure. This increased expression may be a potential mechanism of noise‐induced hearing loss (NIHL) and a possible mechanism of resveratrol's ability to mitigate NIHL by its ability to reduce COX‐2 expression.
Influence of Vestibular Disease on Psychological Distress: A Multicenter Study
Authors: Hong Seok Min , Lee Hyo‐Jeong , Lee Byungho , Park Su‐Kyoung , Hong Sung Kwang , Park Il‐Seok , Kim Yong Bok , Kim Hyung‐Jong
Published: February 2013

Objectives

Some patients with dizziness show high comorbidity with psychiatric disorders. However, the association of vestibular deficit with psychological symptoms remains controversial. Thus, we investigated psychological distress (depression and anxiety) in patients with vestibular disease and examined factors modifying the development of psychological distress in these patients, including age, sex, severity of dizziness symptoms, and type of vestibular disease.

Study Design

Prospective study.

Setting

Tertiary referral center.

Subjects and Methods

This study enrolled 407 patients with dizziness. Dizziness and the psychological symptoms of all patients were measured using the Korean versions of the Dizziness Handicap Inventory (DHI), the Beck Depression Inventory (BDI), and the Spielberger State‐Trait Anxiety Inventory (STAI). We evaluated the influence of vestibular disease type, DHI score, and other factors such as sex and age on the psychological scales (BDI, STAI) through multiple regression analysis.

Results

Only DHI score and vestibular neuritis were related significantly to BDI scores in patients with vestibular disease, and only DHI scores were associated with STAI scores.

Conclusion

Dizziness Handicap Inventory scores and psychological distress were closely associated. Psychological distress might be a consequence of high DHI score rather than of a specific type of vestibular disease, although depressive symptoms were related to vestibular neuritis.
Spinal Meningeal Oligodendrogliomatosis in Two Boxer Dogs
Authors: Kovi R. C. , Wünschmann A. , Armién A. G. , Hall K. , Carlson T. , Shivers J. , Oglesbee M. J.
Published: February 2013

Two Boxer dogs developed progressive ataxia in association with a neoplastic infiltration of the spinal leptomeninges. In the first dog, the leptomeningeal neoplasm encompassed the entire cord and the ventral aspect of the brainstem and extended bilaterally into the piriform lobes. In the second, the neoplasm surrounded the C1–C3 segments of the spinal cord and the brainstem without involvement of the brain or spinal cord parenchyma. In both dogs, the neoplastic cells had variably distinct cell borders, clear to eosinophilic cytoplasm, and a round to ovoid hyperchromatic nucleus. Neoplastic cells were immunopositive for Olig2 and doublecortin in both dogs and for vimentin in one dog but were immunonegative for glial fibrillary acidic protein, S-100, CD34, E-cadherin, cytokeratin, CD3, and CD20. The morphological and immunohistochemical features of the neoplastic cells were consistent with an oligodendrocyte lineage. This hitherto poorly recognized neoplasm in dogs is analogous to human leptomeningeal oligodendrogliomatosis.
Spontaneous Obesity-Linked Type 2 Diabetes in the Absence of Islet Amyloid in a Cynomolgus Monkey Infected With Bovine Spongiform Encephalopathy
Authors: Strom A. , Yutzy B. , Kruip C. , Völker I. , Schloot N. C. , Roden M. , Scott F. W. , Löwer J. , Holznagel E.
Published: February 2013

A 9-year-old cynomolgus monkey ( Macaca fascicularis) infected orally with bovine spongiform encephalopathy (BSE) was presented for necropsy following euthanasia 4 years post infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of type 2 diabetes (T2D). In contrast, macaque R984 developed rapid weight loss, hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet amyloid deposits were present. Immunostaining of pancreas sections for insulin and glucagon confirmed the loss of endocrine cells. In addition, prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal prion spread from the gut during the preclinical phase of BSE infection. Plasma glucose and insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet amyloid deposits could have been due to early prion spread from the periphery to the endocrine system or could have occurred spontaneously.
Lipopolysaccharide Enhances Mouse Lung Tumorigenesis
Authors: Melkamu T. , Qian X. , Upadhyaya P. , O’Sullivan M. G. , Kassie F.
Published: February 2013

The association between pulmonary inflammation and lung cancer is well established. However, currently there are no appropriate models that recapitulate inflammation-related lung cancer in humans. In the present study, we examined, in 2 tumor bioassays, enhancement by bacterial lipopolysaccharide (LPS) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)–induced lung tumorigenesis in A/J mice. Mice that were treated with NNK alone developed 29.6 ± 9.8 and 36.2 ± 4.1 lung tumors per mouse in experiments 1 and 2, respectively. Chronic intranasal instillation of LPS to NNK-treated mice increased the multiplicity of lung tumors to 47.3 ± 16.1 and 51.2 ± 4.8 lung tumors per mouse in experiments 1 and 2, corresponding to a significant increase by 60% and 41%, respectively. Moreover, administration of LPS to NNK-pretreated mice significantly increased the multiplicity of larger tumors and histopathologically more advanced lesions (adenoma with dysplasia and adenocarcinoma), macrophage recruitment to the peritumoral area, and expression of inflammation-, cell proliferation-, and survival-related proteins. Overall, our findings demonstrated the promise of the NNK-LPS-A/J mice model to better understand inflammation-driven lung cancer, dissect the molecular pathways involved, and identify more effective preventive and therapeutic agents against lung cancer.
Effects of Different Anesthetics in the Murine Model of EHV-1 Infection
Authors: Eöry M. L. , Zanuzzi C. N. , Fuentealba N. A. , Sguazza G. H. , Gimeno E. J. , Galosi C. M. , Barbeito C. G.
Published: February 2013

Mice are commonly used as an experimental model to investigate the Equid herpesvirus 1 (EHV-1) infection. This model easily reproduces the disease, and the clinical signs are more or less similar to those observed in the horse, the natural host. During natural infection, the acute course of respiratory infection is mandatory for the development of adaptive immune response. Since interactions between EHV-1 and anesthetics are possible, the study investigated whether the early events of murine pulmonary immune response could be affected by different anesthetics. Therefore, mice were experimentally infected with a unique EHV-1 strain under the effects of ether, ketamine/xylazine, or isoflurane. Clinical signs and histopathological lesions in the lungs were described, and the cell death and proliferation rates of sham-inoculated or infected animals were quantified using immunohistochemistry. Clinical signs were more severe in animals anesthetized with ether. Qualitative differences in the recruited inflammatory cells were observed following application of anesthesia. The level of infection between the infected groups was not statistically significant. However, lungs from ketamine/xylazine-anesthetized animals showed the highest cell death rates, whereas those from isoflurane-anesthetized animals showed the highest proliferation rates. It has been emphasized that anesthetics alone or their interactions with EHV-1 modify the response against the infection. An appropriate selection of the anesthetic during experimental studies is relevant to minimize wrong conclusions.
Environmental evaluation of waste treatment scenarios for the towns Khanty-Mansiysk and Surgut, Russia
Authors: Kaazke Julia , Meneses Montse , Wilke Berndt-Michael , Rotter Vera Susanne
Published: February 2013

Khanty-Mansiysk Autonomous Okrug – Ugra in Siberia has recently started to play a major role in the Russian economy because key oil and gas extraction sites are located in this region. As a result, the extensions of infrastructure and higher incomes have been leading to an accelerated population growth and consequent increase in the generation of solid household waste. The current methods of waste disposal have now reached their limits, especially in the towns Khanty-Mansiysk and Surgut. The key objectives of this study were to identify the influence of waste composition and transport routes on the life cycle assessment (LCA) results and to assess the current waste treatment option for solid household waste and to compare it with proposed scenarios. Furthermore, recommendations for an optimal use of LCA within a decision-making process for a waste management plan are presented. LCA methodology was used to evaluate different waste management scenarios such as landfilling and incineration. One result was that the options ‘incineration with recycling’ and ‘anaerobic mechanical–biological treatment with recycling’ demonstrated lower environmental impact in both Khanty-Mansiysk and Surgut. Another finding was that there were hardly any differences in the ranking of the scenarios for Surgut and Khanty-Mansiysk. However, the special socio-cultural circumstances and location of each town have to be considered seriously in the development of a sustainable waste management plan.
Potential for energy generation from anaerobic digestion of food waste in Australia
Authors: Lou Xian Fang , Nair Jaya , Ho Goen
Published: February 2013

Published national and state reports have revealed that Australia deposits an average of 16 million Mg of solid waste into landfills yearly, of which approximately 12.6% is comprised of food. Being highly biodegradable and possessing high energy content, anaerobic digestion offers an attractive treatment option alternative to landfilling. The present study attempted to identify the theoretical maximum benefit of food waste digestion in Australia with regard to energy recovery and waste diversion from landfills. The study also assessed the scope for anaerobic process to utilize waste for energy projects through various case study scenarios. Results indicated anaerobic digestion of total food waste generated across multiple sites in Australia could generate 558 453 dam3 of methane which translated to 20.3 PJ of heating potential or 1915 GWe in electricity generation annually. This would contribute to 3.5% of total current energy supply from renewable sources. Energy contribution from anaerobic digestion of food waste to the total energy requirement in Australia remains low, partially due to the high energy consumption of the country. However its appropriateness in low density regions, which are prevalent in Australia, may allow digesters to have a niche application in the country.
The Question of Radicalism in Sheldon Wolin’s Political Thought: A Marxist Perspective
Authors: Moraitis Yiorgos
Published: February 2013

It is widely accepted that Sheldon Wolin has revitalized the tradition of radicalism in the context of modern political thought, as evidenced by his contribution to the debate on the so-called death of political philosophy and his forceful critique of Rawls and modern political liberalism. However, Wolin’s fugitive democracy has met with opposition. This paper investigates fugitive democracy from a Marxist perspective and questions whether fugitive democracy can actually confront crucial socio-political issues such as the lack of democracy for the masses in the production of social wealth. Moreover, Wolin’s misinterpretation and rejection of Marx’s theory of democracy and politics leads him to a misconceived view of the Marxian philosophy of history and the progress of political societies as a whole, a misconception that leads to inconsistencies within his own work. And finally, although Wolin seems to be a radical democrat and appears to hold a worldview close to that of socialists, he in fact, despite his criticisms, follows a liberal logic.
Capitalist Development and the Rise and ‘Fall’ of the Far-Right
Authors: Saull Richard
Published: February 2013

This article offers an alternative account of the European far-right from those prevailing in comparative politics and the history of ideas literatures. The article focuses on: (i) the historical evolution of the European far-right from its late 19th-century origins to its contemporary form as a current of anti-globalization; and (ii) the way in which international capitalist development explains the generalized emergence and ‘success’ of the far-right. I argue that uneven capitalist development has been integral to the evolution of the far-right. It has been the geopolitical expressions of capitalist development that best account for enabling domestic political contexts that have facilitated far-right mobilizations. Consequently, whilst the far-right has re-emerged, because of the post-1945 decoupling of uneven capitalist development from geopolitical rivalry, the international and domestic social, political and ideological resources that the contemporary far-right can draw upon are considerably weaker than the historical far-right.
Ideology and Brand Consumption
Authors: Khan Romana , Misra Kanishka , Singh Vishal
Published: February 2013

Do mundane daily choices, such as what brands people buy in a supermarket, reflect aspects of values and ideologies? This article presents a large-scale field study performed to determine whether traits associated with a conservative ideology, as measured by voting behavior and religiosity, are manifested in consumers’ routine, seemingly inconsequential product choices. Our analysis of market shares for a variety of frequently purchased products shows that both of these measures of conservatism are associated with a systematic preference for established national brands (as opposed to their generic substitutes) and with a lower propensity to buy newly launched products. These tendencies correspond with other psychological traits associated with a conservative ideology, such as preference for tradition and the status quo, avoidance of ambiguity and uncertainty, and skepticism about new experiences.
Another Perspective
Authors: Altman Barbara M.
Published: February 2013

A new criticism of the variety in measures serving to identify the disabled population in the American Community Survey (ACS) has been raised by Burkhauser, Houtenville, and Tennant. That criticism identifies the lack of a participation component, specifically a measure of work limitation, as creating bias resulting in an underestimate of the size of the working-age population with disabilities. The purpose of this article is to provide another perspective on the relationship of the current ACS measure and a work limitation measure demonstrating the complications introduced by combining measures that represent two different metrics and introducing an unmeasured environmental element. The relationship of the measures with receipt of Social Security Disability Insurance or Supplemental Security Insurance is also examined and discussed.
If the Book Fits
Authors: Leko Melinda M. , Mundy Charlotte A. , Kang Hyun-Ju , Datar Sujata D.
Published: February 2013

Many adolescents with learning disabilities (LD) experience difficulties reading. To improve reading outcomes for these students, research has demonstrated the importance of providing students with appropriate texts. Appropriate texts are those that match both the reading and interest levels of students and are often credited with reducing frustration and facilitating comprehension. This article presents research on selecting appropriate texts and provides teachers with practical suggestions and resources to use when supporting selection of independent reading material for adolescents with LD.
Role of Preoperative Computed Tomography Scans in Operative Planning for Malleolar Ankle Fractures
Authors: Black Eric M. , Antoci Valentin , Lee Jared T. , Weaver Michael J. , Johnson A. Holly , Susarla Seenu M. , Kwon John Y.
Published: February 2013

Background:

There remains no consensus regarding the role of computed tomography (CT) scans in preoperative planning for malleolar ankle fractures. The aim of this study was to determine the role of preoperative CT scans on operative planning in these fractures.

Methods:

A retrospective analysis was performed on 100 consecutive patients treated at our institution for malleolar ankle fractures (AO type 44) with both preoperative radiographs and CT scans. Six study participants reviewed available radiographs and formulated an operative (or nonoperative) plan including positioning, operative approach, and fixation. Participants then analyzed CT scans of the same fractures, deciding whether (and how) they would alter operative strategy. Characteristics of fractures and radiographs were correlated with changes in operative strategy.

Results:

Operative strategy was notably changed in 24% of cases after CT review, with strong intraclass correlation (0.733). Common changes included alterations in medial malleolar (21%) or posterior malleolar (15%) fixation and fixation of an occult anterolateral plafond fracture (9%). Notable predictors of changes in operative strategy included trimalleolar over unimalleolar fractures (29% vs 10% rate of change), preoperative dislocation over no dislocation (31% vs 20%), the presence of only radiographs with overlying plaster versus fractures with at least 1 set of radiographs without plaster (25% vs 14%), and suprasyndesmotic versus trans- and infra-syndesmotic fractures (40% vs 20% and 4%, respectively).

Conclusions:

CT scans may be useful adjuncts in preoperative planning for malleolar ankle fractures, most notably in fracture dislocations, cases in which all available radiographs are obscured by plaster, trimalleolar fractures, and suprasyndesmotic fractures.

Level of Evidence:

Level III, retrospective comparative study.
The effects of pre-harvest application of aminoethoxyvinylglycine on the bioactive compounds and fruit quality of ‘Fortune’ plum variety during cold storage
Authors: Karaman Sedat , Ozturk Burhan , Aksit Huseyin , Erdogdu Tugce
Published: February 2013

The effects of pre-harvest aminoethoxyvinylglycine treatments on fruit quality parameters and bioactive compounds of ‘Fortune’ plum during cold storage were investigated. Two different aminoethoxyvinylglycine doses were applied to plum trees two weeks prior to the estimated harvest date, and harvested fruit samples were kept in cold storage at 0 oC temperature and with 90 ± 5% relative humidity for 4 weeks. Lightness ( L*) and hue angle values decreased in all treatments during cold storage. Weight loss (%) was significantly decreased ( p < 0.05) with 100 mg/L aminoethoxyvinylglycine treatment at the end of the storage. Fruit firmness at the end of the storage was significantly increased with aminoethoxyvinylglycine treatments. Total phenolics and total antioxidant activity were increased with aminoethoxyvinylglycine treatments till the 21st day of storage and decreased by the 28th day. Total phenolics and total antioxidant activity were significantly decreased ( p < 0.05) with the 200 mg/L aminoethoxyvinylglycine treatment at the end of storage. Rutin was significantly decreased with 100 mg/L aminoethoxyvinylglycine treatment at the end of cold storage.
Effectiveness of Computerized Working Memory Training Program in Chinese Community Settings for Children With Poor Working Memory
Authors: Wong Ann S. Y. , He Moon Y. Q. , Chan Raymond W. S.
Published: February 2013

Objective: The purpose of the study is to further examine the effectiveness of computerized working memory intervention among Chinese population. Method: In comparing the performance of experimental group with those of control group, General Linear Model Analysis (repeated measures) was applied to neurological and behavioral measures obtained for working memory, response inhibition, and inattention and hyperactive symptoms. Results: For experimental group that received high-intensity training in school setting, there was a significant improvement in working memory reflected in neuropsychological measures as well as parent-rated behavioral measures as compared with the control group. Conclusion: Our results generally supported the effectiveness of group-based computerized training. It might be served as a cost-effective intervention in semistructured settings, with high-intensity training and minimal therapist involvement.
Behavioral Assessment of Core ADHD Symptoms Using the QbTest
Authors: Reh Verena , Schmidt Martin , Lam Le , Schimmelmann Benno G. , Hebebrand Johannes , Rief Winfried , Christiansen Hanna
Published: February 2013

Objective: Hyperactivity, one of the core symptoms of ADHD, has been mostly neglected in neuropsychological assessment of childhood ADHD. The neuropsychological Quantified behavior Test (QbTest) separately assesses all three core symptoms of ADHD on a behavioral level. Factor structure of the QbTest and its concurrent and discriminant validity are presented. Method: An exploratory factor analysis (n = 828 children) was performed. In a second sample (n = 102 children) a Multi-Trait-Multi-Method (MTMM) approach was used for validity analyses. Results: A three factorial model explained 76 % of the total variance, with the resulting QbTest factors significantly influenced by age and gender. The MTMM approach yielded promising results for discriminant, yet inconsistent findings for concurrent validity between the QbTest and another attention test as well as for Conners’ Parent and Teacher Rating Scales. Conclusion: Results indicate that the QbTest may be helpful for the behavioral assessment of childhood ADHD, yet further studies on its psychometric quality and clinical utility are needed.
Attentional Networks in Boys With ADHD or Autism Spectrum Disorder and the Relationship With Effortful Control
Authors: Samyn Vicky , Roeyers Herbert , Bijttebier Patricia , Wiersema Jan R.
Published: February 2013

Objective: The present study investigated differences in attentional networks in typically developing (TD) boys and boys with ADHD or autism spectrum disorder (ASD). In addition, we investigated the relationship between networks and the relationship with effortful control (EC). Method: An Attention Network Test was used to assess alerting, orienting, and executive attention in 25 TD boys, 25 boys with ADHD, and 25 boys with ASD. Results: In the absence of warning signals, boys with ADHD performed poorer than other children. In all groups, the orienting and executive control networks and the alerting and orienting networks interacted. Executive attention and EC were unrelated. Conclusion: Results provided evidence of impaired tonic alertness in ADHD and support the idea of functional integration of attentional networks. Finally, findings suggest that the link between EC reports and indices of neural systems involved in the effortful regulation of behavior may not be as unambiguous as previously thought.
Young people and health: Towards a new conceptual framework for understanding empowerment
Authors: Spencer Grace
Published: February 2013

In recent times, empowerment has become the focus of much work with young people amidst increasing concerns about their health. Empowerment is often offered as a ‘solution’ to such concerns, with the uncritical assumption being made that empowerment unproblematically results in positive health outcomes. While much of the health promotion literature advocates ‘empowerment’, it often does so without offering a clear conceptualisation of the word itself or indeed addressing the thorny theoretical tensions surrounding the concept’s root word of power. In light of this omission, this article offers a more theoretically informed conceptualisation of empowerment and considers the relationship to young people’s health. This article outlines a more dynamic and generative conceptualisation of empowerment than hitherto articulated in the literature, informed by Lukes’ multidimensional perspective of power. Drawing on findings from an ethnographic study on empowerment and young people’s health, this article develops six conceptually distinct forms of empowerment ( impositional, dispositional, concessional, oppositional, normative and transformative). Data were collected from 55 young men and women aged 15–16 years through group discussions, individual interviews and observational work in a school and surrounding community settings in England. Crucially, these six new forms of empowerment capture and synthesise individual, structural and ideological elements of power that differentially, and sometimes inconsistently, shape the possibilities for young people’s empowerment. Of significance is the way in which these different forms of empowerment intersect to (re)produce relations of power and may offer different possibilities for health promotion.
Concrete matters: Ruins of modernity and the things called heritage
Authors: Pétursdóttir Þóra
Published: February 2013

Intangibility has become a trendy term within heritage studies and is now even considered to refer to heritage in general. This article discusses this development, along with its integrity and consequences for the fate of things in the heritage discourse. With reference to the concrete ruins of Iceland’s recent past it addresses the traditional and contemporary processes of discrimination and othering within heritage definitions, and the often fragile dialectic between heritage and waste. With a foothold in these very concrete and tangible remains the article questions the emerging claim ‘that all heritage is intangible’ and suggests that a broader heritage conception, and a true concern for the very tangible qualities of things, may bring us closer to a comprehension of the (heritage) value of these modern ruins.
The rediscovery of HMS Investigator: Archaeology, sovereignty and the colonial legacy in Canada’s Arctic
Authors: Hodgetts Lisa M.
Published: February 2013

HMS Investigator, the British Navy vessel that discovered the North-West Passage in 1850, helped to stake Britain’s claim to Arctic territory. Her crew’s colonial attitudes towards the Indigenous Inuit inhabitants of the region have been perpetuated in archaeological interpretations of the ship’s impact on local Inuit communities and in media coverage of the rediscovery of the ship by archaeologists in 2010, which framed the ship as a symbol of Canada’s Arctic sovereignty. As climate change continues to fuel international debates about the control of Arctic resources and to negatively impact the Arctic archaeological record, Arctic archaeology promises to become increasingly political. In the Canadian Arctic, a range of collaborative projects that bring together archaeologists and Inuit community groups to better understand the human history of the north have made important steps towards decolonizing our discipline and could ripple outwards to support Inuit demands for a voice in international debates about Arctic sovereignty. Should we choose, these projects could also work to change the way the past is mobilized and presented beyond archaeological circles, contributing more directly to social justice on a broader scale.
Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients
Authors: Lim Su Chi , Liu Jian-Jun , Subramaniam Tavintharan , Sum Chee Fang
Published: February 2013

Introduction:

The aging-suppression gene α-klotho is potentially reno-protective. Animal studies suggest that angiotensin II may be a negative regulator of α-klotho expression. Therefore, we hypothesize that renin–angiotensin system antagonism may increase α-klotho secretion in type 2 diabetes (T2DM).

Subjects and methods:

In this post-hoc analysis of a randomized crossover study, 33 T2DM subjects with albuminuria received either 50 mg of losartan or 20 mg of quinapril (both 50% maximal dose) daily for 4 weeks with 4-week wash-out period in between.

Results:

Our data showed that losartan, but not quinapril, significantly increased circulating α-klotho level by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Linear regression revealed that, besides different mode of treatment, increment in plasma α-klotho was associated with decrement in urine albumin/creatinine ratio (β=-0.263, p=0.029).

Conclusions:

The angiotensin receptor blocker losartan increases circulating α-klotho in T2DM with albuminuria. The clinical significance of this rise in α-klotho associated with losartan intervention deserves further investigation.
Delayed targeting of CD39 to activated platelet GPIIb/IIIa via a single-chain antibody: breaking the link between antithrombotic potency and bleeding?
Authors: Hohmann Jan David , Wang Xiaowei , Krajewski Stefanie , Selan Carly , Haller Carolyn A. , Straub Andreas , Chaikof Elliot L. , Nandurkar Harshal H. , Hagemeyer Christoph E. , Peter Karlheinz
Published: February 2013

Key Points

Targeting of an anticlotting drug to activated platelets promises effective blood clot prevention without bleeding side effects.
Analysis of the leaf transcriptome of Musa acuminata during interaction with Mycosphaerella musicola: gene assembly, annotation and marker development
Authors: Passos Marco A N , de Cruz Viviane Oliveira , Emediato Flavia L , de Teixeira Cristiane Camargo , Azevedo Vânia C Rennó , Brasileiro Ana C M , Amorim Edson P , Ferreira Claudia F , Martins Natalia F , Togawa Roberto C , Júnior Georgios J Pappas , da Silva Orzenil Bonfim , Miller Robert NG
Published: February 2013

Background

Although banana (Musa sp.) is an important edible crop, contributing towards poverty alleviation and food security, limited transcriptome datasets are available for use in accelerated molecular-based breeding in this genus. 454 GS-FLX Titanium technology was employed to determine the sequence of gene transcripts in genotypes of Musa acuminata ssp. burmannicoides Calcutta 4 and M. acuminata subgroup Cavendish cv. Grande Naine, contrasting in resistance to the fungal pathogen Mycosphaerella musicola, causal organism of Sigatoka leaf spot disease. To enrich for transcripts under biotic stress responses, full length-enriched cDNA libraries were prepared from whole plant leaf materials, both uninfected and artificially challenged with pathogen conidiospores.

Results

The study generated 846,762 high quality sequence reads, with an average length of 334 bp and totalling 283 Mbp. De novo assembly generated 36,384 and 35,269 unigene sequences for M. acuminata Calcutta 4 and Cavendish Grande Naine, respectively. A total of 64.4% of the unigenes were annotated through Basic Local Alignment Search Tool (BLAST) similarity analyses against public databases.

Assembled sequences were functionally mapped to Gene Ontology (GO) terms, with unigene functions covering a diverse range of molecular functions, biological processes and cellular components. Genes from a number of defense-related pathways were observed in transcripts from each cDNA library. Over 99% of contig unigenes mapped to exon regions in the reference M. acuminata DH Pahang whole genome sequence. A total of 4068 genic-SSR loci were identified in Calcutta 4 and 4095 in Cavendish Grande Naine. A subset of 95 potential defense-related gene-derived simple sequence repeat (SSR) loci were validated for specific amplification and polymorphism across M. acuminata accessions. Fourteen loci were polymorphic, with alleles per polymorphic locus ranging from 3 to 8 and polymorphism information content ranging from 0.34 to 0.82.

Conclusions

A large set of unigenes were characterized in this study for both M. acuminata Calcutta 4 and Cavendish Grande Naine, increasing the number of public domain Musa ESTs. This transcriptome is an invaluable resource for furthering our understanding of biological processes elicited during biotic stresses in Musa. Gene-based markers will facilitate molecular breeding strategies, forming the basis of genetic linkage mapping and analysis of quantitative trait loci.
Comparative genomics of Lupinus angustifolius gene-rich regions: BAC library exploration, genetic mapping and cytogenetics
Authors: Książkiewicz Michał , Wyrwa Katarzyna , Szczepaniak Anna , Rychel Sandra , Majcherkiewicz Karolina , Przysiecka Łucja , Karlowski Wojciech , Wolko Bogdan , Naganowska Barbara
Published: February 2013

Background

The narrow-leafed lupin, Lupinus angustifolius L., is a grain legume species with a relatively compact genome. The species has 2n = 40 chromosomes and its genome size is 960 Mbp/1C. During the last decade, L. angustifolius genomic studies have achieved several milestones, such as molecular-marker development, linkage maps, and bacterial artificial chromosome (BAC) libraries. Here, these resources were integratively used to identify and sequence two gene-rich regions (GRRs) of the genome.

Results

The genome was screened with a probe representing the sequence of a microsatellite fragment length polymorphism (MFLP) marker linked to Phomopsis stem blight resistance. BAC clones selected by hybridization were subjected to restriction fingerprinting and contig assembly, and 232 BAC-ends were sequenced and annotated. BAC fluorescence in situ hybridization (BAC-FISH) identified eight single-locus clones. Based on physical mapping, cytogenetic localization, and BAC-end annotation, five clones were chosen for sequencing. Within the sequences of clones that hybridized in FISH to a single-locus, two large GRRs were identified. The GRRs showed strong and conserved synteny to Glycine max duplicated genome regions, illustrated by both identical gene order and parallel orientation. In contrast, in the clones with dispersed FISH signals, more than one-third of sequences were transposable elements. Sequenced, single-locus clones were used to develop 12 genetic markers, increasing the number of L. angustifolius chromosomes linked to appropriate linkage groups by five pairs.

Conclusions

In general, probes originating from MFLP sequences can assist genome screening and gene discovery. However, such probes are not useful for positional cloning, because they tend to hybridize to numerous loci. GRRs identified in L. angustifolius contained a low number of interspersed repeats and had a high level of synteny to the genome of the model legume G. max. Our results showed that not only was the gene nucleotide sequence conserved between soybean and lupin GRRs, but the order and orientation of particular genes in syntenic blocks was homologous, as well. These findings will be valuable to the forthcoming sequencing of the lupin genome.
Comparative genomic analyses of Mycoplasma hyopneumoniae pathogenic 168 strain and its high-passaged attenuated strain
Authors: Liu Wei , Xiao Shaobo , Li Mao , Guo Shaohua , Li Sha , Luo Rui , Feng Zhixin , Li Bin , Zhou Zhemin , Shao Guoqing , Chen Huanchun , Fang Liurong
Published: February 2013

Background

Mycoplasma hyopneumoniaeis the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants ofM. hyopneumoniae, we determined the whole genome sequence ofM. hyopneumoniaestrain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses.

Results

We performed the first comprehensive analysis ofM. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence.

Conclusions

We studied the virulence attenuation mechanism ofM. hyopneumoniaeby comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form the foundation of future investigations into the pathogenesis ofM. hyopneumoniaeand facilitate the design of new vaccines.
Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: Chikungunya seroprevalence results from the Malaysian Cohort
Authors: Azami Nor Azila Muhammad , Salleh Sharifah Azura , Shah Shamsul Azhar , Neoh Hui-min , Othman Zulhabri , Zakaria Syed Zulkifli Syed , Jamal Rahman
Published: February 2013

Background

In 1998, Malaysia experienced its first chikungunya virus (CHIKV) outbreak in the suburban areas followed by another two in 2006 (rural areas) and 2008 (urban areas), respectively. Nevertheless, there is still a lack of documented data regarding the magnitude of CHIKV exposure in the Malaysian population. The aim of this study was to determine the extent of chikungunya virus infection in healthy Malaysian adults residing in outbreak-free locations.

Methods

A cross sectional study of chikungunya (CHIK) seroprevalence was carried out in 2009 amongst The Malaysian Cohort participants living in four states (Kuala Lumpur, Selangor, Pahang and Negeri Sembilan). A total of 945 participants were randomly identified for the study. Potential risk factors for CHIK infection were determined via questionnaires, and IgG antibodies against CHIK were detected by an enzyme-linked immunosorbent assay. Logistic regression identified risk factors associated with CHIK seropositivity, while geographical information system was used for visual and spatial analysis.

Results

From the 945 serum samples tested, 5.9% was positive for CHIK IgG. Being male, Malay, rural occupancy and Negeri Sembilan residency were identified as univariate predictors for CHIK seropositivity, while multivariate analysis identified being male and rural occupancy as risk factors.

Conclusions

This study provided evidence that CHIK is slowly emerging in Malaysia. Although the current baseline seroprevalence is low in this country, increasing number of CHIK cases reported to the Malaysia Ministry of Health imply the possibility of CHIK virus becoming endemic in Malaysia.
Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database
Authors: Huang Baojun , Sun Zhe , Wang Zhenning , Lu Chong , Xing Chengzhong , Zhao Bo , Xu Huimian
Published: February 2013

Background

Peritoneal dissemination is the most common type of recurrence in advanced gastric cancer. The main mechanism is thought to be via the exfoliation of free cancer cells (FCCs) from tumor in the gastric serosa. The frequency of recurrence thus increases once the tumor cells penetrate the serosa. However, this type of recurrence also occurs in patients without serosal invasion, though the mechanisms responsible for have not been fully established. We therefore investigated the factors associated with peritoneal dissemination in patients with non-serosa-invasive gastric cancer.

Methods

A total of 685 patients with non-serosa-invasive gastric cancer who underwent curative resection with retrieval of more than 15 nodes were selected. The associations between clinicopathological features and peritoneal dissemination were analyzed. Among them, the tumor infiltrating growth pattern (INF) were classified into α, β and γ according to the Japanese Classification of Gastric Carcinoma (JCGC).

Results

The overall incidence of peritoneal metastasis was 20% (137/685). Age, Borrmann type, differentiation, INF, nodal status and free cancer cells (FCCs) were correlated with peritoneal dissemination using univariate analysis. However, only INF, Borrmann type and TNM node stage were identified as independent correlated factors with peritoneal metastasis by multivariate analysis when FCCs were excluded, and these were also prognostic factors. Peritoneal dissemination was more common in patients with INFγ, Borrmann III/IV and N3 stage. Among patients without FCCs, nodal involvement or vessel invasion, only INF remained an independent associated factor according to multivariate analysis.

Conclusions

Tumor infiltrating growth pattern (INF), together with Borrmann type and TNM node stage, are important factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer.
IL-22 is related to development of human colon cancer by activation of STAT3
Authors: Jiang Runqiu , Wang Haiyang , Deng Lei , Hou Jiajie , Shi Ruihua , Yao Ming , Gao Yun , Yao Aihua , Wang Xuehao , Yu Lianzhen , Sun Beicheng
Published: February 2013

Background

It has been previously reported that IL-22, one of the cytokines secreted by Th17 cells, demonstrates both a protective and inflammatory promotion effect in inflammatory bowel disease (IBD) through STAT3 signaling activation. We sought to investigate the role of IL-22 expression in colon cancer (CC).

Methods

The expression of IL-22 and related molecules were detected in human CC, the detail function and mechanism of IL-22 were investigated by in vivo and in vitro model.

Results

Our results demonstrated significant upregulation of IL-22 in human CC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, our findings demonstrated that IL-22 expression was significantly higher in ulcerative colitis (UC) tissues versus normal colon tissues. Both IL-22 receptor α1 (IL-22RA1) and IL-23 were highly expressed in CC and UC tissues compared to normal controls. TILs exhibiting various IL-22 expression levels isolated from CC patients were demonstrated to enhance tumor growth and metastasis co-transplanted with Hct-116 cells underwent subcutaneous transplantation in mice model. Tumor growth and metastasis was promoted by STAT3 phosphorylation and upregulation of its downstream genes such as Bcl-xl, CyclinD1, and VEGF. In vitro studies confirmed the anti-apoptotic and pro-proliferation effect of IL-22 according to the BrdU cooperation assay and peroxide induced apoptosis analysis with or without the presence of IL-22.

Conclusion

In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation.
Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program
Authors: Sruamsiri Rosarin , Chaiyakunapruk Nathorn , Pakakasama Samart , Sirireung Somtawin , Sripaiboonkij Nintita , Bunworasate Udomsak , Hongeng Suradej
Published: February 2013

Background

Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand.

Methods

A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty.

Results

In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients.

Conclusion

At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.