bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation
Authors: Dalaklioglu S. , Genc G.E. , Aksoy N.H. , Akcit F. , Gumuslu S.
Published: February 2013

Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4′-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione- S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.
Evaluation of the mutagenic potential and acute oral toxicity of standardized extract of Ocimum sanctum (OciBest™)
Authors: Chandrasekaran C.V. , Srikanth H.S. , Anand M.S. , Allan J. Joshua , Viji M. M. Hipolith , Amit A.
Published: February 2013

Ocimum sanctum L. (Lamiaceae) is found throughout India and in many parts of world. O. sanctum is used for the treatment of various health indications. In this lieu, it is of prime importance to investigate the safety aspects of the plant. Hence, the present study was conducted to investigate the possible genotoxic potential and acute oral toxicity of the extract of O. sanctum (OciBest™). The standard battery of in vitro genotoxicity tests, namely bacterial reverse mutation, chromosome aberration and micronucleus (MN) tests were employed to assess the possible mutagenic activity. The results showed that OciBest™ (7.9–2500.0 µg/mL) did not increase the number of histidine revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with and without exogenous metabolic activation (S9). OciBest™ (10.0–100.0 µg/mL) did not show structural chromosomal aberrations or increase in MN induction, with and without S9, at the tested dose range in both 4-h and 18-h exposure cell cultures. Thus, OciBest™ is not genotoxic in bacterial reverse mutation, chromosomal aberration and MN tests. In an acute oral toxicity test, rats were treated with 5 g/kg of OciBest™ and observed for signs of toxicity for 14 days and the results did not show any treatment-related toxic effects to Wistar rats.
Rutin- and Selenium-attenuated cadmium-induced testicular pathophysiology in rats
Authors: Abarikwu S.O. , Iserhienrhien B.O. , Badejo T.A.
Published: February 2013

Cadmium (Cd) is known to cause oxidative damage in the testes of rats. The aim of this study was to investigate the protective role of rutin (RUT, 30 mg/kg) and selenium (Se, 0.15 ppm) alone or in combination against Cd (200 ppm)-induced lipid peroxidation, steroidogenesis and changes in antioxidant defence system in the rat testes. The obtained results showed that Cd increased lipid peroxidation and abnormal sperm count and decreased plasma testosterone, lactate dehydrogenase, acid phosphatase, alkaline phosphatase and testicular steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD activities as well as epididymal sperm counts and motility, while RUT and Se treatment reversed this change to control values. Acute intoxication with Cd was also followed by significantly decreased activity of the antioxidant defence system (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione (GSH), and glutathione-S-transferase (GST)). Treatment with RUT and Se reversed Cd-induced alterations of antioxidant defence system and significantly prevented Cd-induced testes damage and depletion of plasma and testicular Se levels. RUT and Se appear not to have more profound effects than their separate effects against Cd-induced testicular toxicity, although Se was more potent than RUT in the recovery of testosterone levels. These results suggest that both RUT and Se do not have synergistic role against Cd-induced testicular injury.
Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation-induced hepatic fibrosis in rats
Authors: Lim J-H , Kim T-W , Song I-B , Park S-J , Kim M-S , Cho E-S , Jung J-Y , Son H-Y , Kim J-W , Yun H-I
Published: February 2013

The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bile duct ligation (BDL)-induced hepatic fibrosis in rats. BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days. Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-β1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO). The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson’s trichrome stain. ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group. These elevations were significantly decreased by BC703 treatment. Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group. In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment. Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-β1. Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat. BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease.
Probucol and the cholesterol synthesis inhibitors simvastatin and triparanol regulate Iks channel function differently
Authors: Hihara Taro , Taniguchi Tomohiko , Ueda Masataka , Yoshinaga Takashi , Miyamoto Norimasa , Sawada Kohei
Published: February 2013

Channels responsible for slowly activating delayed-rectifier potassium current ( IKs) are composed of KCNQ1 and KCNE1 subunits, and these channels play a role in the repolarization of cardiac action potentials. Recently, we showed that the antihyperlipidemic drug probucol, which induces QT prolongation, decreases the IKs after 24-h treatment. In the present study, we investigated the effects of three cholesterol-lowering agents (probucol, an enhancer of cholesterol efflux; simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor; and triparanol, a 3β-hydroxysterol-▵24-reductase inhibitor) on cholesterol synthesis, the KCNQ1 current ( IKCNQ1), and the IKs to clarify the differences in the modes of action of these agents on the IKs. Probucol did not inhibit cholesterol synthesis and had no effect on IKCNQ1, while IKs decreased after 24-h treatment. Simvastatin inhibited cholesterol synthesis and decreased IKCNQ1 and IKs. Additionally, the activation kinetics of IKs became faster, compared with that of control IKs. Triparanol inhibited cholesterol synthesis but did not reduce IKCNQ1 and IKs. However, the activation kinetics of IKs became faster. Our data indicated that the mechanism by which probucol inhibits IKs was not mediated by the inhibition of cholesterol synthesis but depended on an interaction with the KCNQ1/KCNE1 complex. Meanwhile, the reduction in cholesterol induced by simvastatin and triparanol is one of the mechanisms that affects the kinetics of Iks.
The role of serum cholinesterase activity and S100B protein in the evaluation of organophosphate poisoning
Authors: Yardan T. , Baydin A. , Acar E. , Ulger F. , Aygun D. , Duzgun A. , Nar R.
Published: February 2013

The aim of this study was to investigate the role of serum cholinesterase (SChE) activity and S100B protein in the evaluation of patients with acute organophosphate (OP) poisoning. Patients with acute OP poisoning admitted to the emergency department were included in this cross-sectional study. Twenty healthy volunteers served as controls. The SChE activity and serum S100B were determined on admission. Patients were divided into two groups (low severity and high severity). Thirty-six patients diagnosed with acute OP poisoning were enrolled. Serum S100B concentrations were higher in patients than in the control group ( p < 0.05). In the high-severity group, the SChE levels were lower and the S100Bs levels were higher than in the low-severity group. The SChE level was not different between survivors and nonsurvivors. S100B levels were higher in nonsurvivors than in survivors. According to receiver–operating characteristic curve analysis, the optimal cutoff value of serum S100B level to predict mortality was 236.5 pg/mL, with 71.4% sensitivity and 89.7% specificity. Our data suggest that initial SChE level is related to the clinical severity but not with mortality. S100B may be a useful marker in the assessment of clinical severity and prediction of mortality in acute OP poisoning.
How has neuroscience affected lay understandings of personhood? A review of the evidence
Authors: O’Connor Cliodhna , Joffe Helene
Published: February 2013

The prominence of neuroscience in the public sphere has escalated in recent years, provoking questions about how the public engages with neuroscientific ideas. Commentaries on neuroscience’s role in society often present it as having revolutionary implications, fundamentally overturning established beliefs about personhood. The purpose of this article is to collate and review the extant empirical evidence on the influence of neuroscience on commonsense understandings of personhood. The article evaluates the scope of neuroscience’s presence in public consciousness and examines the empirical evidence for three frequently encountered claims about neuroscience’s societal influence: that neuroscience fosters a conception of the self that is based in biology, that neuroscience promotes conceptions of individual fate as predetermined, and that neuroscience attenuates the stigma attached to particular social categories. It concludes that many neuroscientific ideas have assimilated in ways that perpetuate rather than challenge existing modes of understanding self, others and society.
Garters on the gridiron: A critical reading of the lingerie football league
Authors: Knapp Bobbi A
Published: February 2013

Using a reading sport methodology, this study examined the Lingerie Football League (LFL) through a critical feminist lens to explore how cultural definitions of femininity, as intersected with race and sexuality, were (re)produced and challenged in texts of the LFL. This analysis was based on the examination of 380 newspaper and magazine articles and web blogs as well as content from the LFL website. The data were collected using LexisNexis and then coded using inductive themes. The five major themes developed included: (1) just another form of soft porn, (2) real women play lingerie football, (3) men take care of business, (4) promoting white-defined beauty, and (5) narratives of empowerment. The findings indicate that a dominant white, heterosexy femininity infused the league and its representations at the point at which the league was established.
Adapting Lymphedema Treatment to the Palliative Setting
Authors: Cheville Andrea Lynne , Andrews Karen , Kollasch Jenny , Schmidt Kenley , Basford Jeffrey
Published: February 2013

Objective:

To review the benefits of adapting the complex techniques of formal lymphedema therapy to the more generalized forms of edema often seen in the chronic disease and palliative care settings.

Data Sources:

Peer-reviewed literature and clinical practice.

Conclusion:

Lymphedema treatment modalities have much to offer beyond their well-characterized benefit in classical lymphedema. In modified forms, they may improve and lessen the burden of refractory edema originating from a diverse range of causes. Thoughtful planning and practice, however, are essential as an inadequate adaptation may result in unnecessary effort, injury for the patient, or an unsatisfactory outcome.
Iraqi American Refugee Youths’ Exposure to Violence
Authors: Black Beverly M. , Chiodo Lisa M. , Weisz Arlene N. , Elias-Lambert Nada , Kernsmith Poco D. , Yoon Jina S. , Lewandowski Linda A.
Published: February 2013

This exploratory study examines the relationships between exposure to violence in the community, school, home and dating relationships among Iraqi American youth. As Iraqi American youth are traditionally not allowed to date, dating violence measures focused on attitudes about and perceptions of abuse occurring in the relationships of friends. The number of friends known who were secretly dating was the most significant predictor of acceptability of dating violence and perceived prevalence of abuse. Youth who experienced child abuse perceived higher rates of dating violence among their peers. Findings highlight the complexities of prevention and intervention of teen dating violence within secretive relationships.
Teacher Ratings of the ADHD-RS IV in a Community Sample
Authors: Caci Hervé M. , Morin Alexandre J. , Tran Antoine
Published: February 2013

Objective: Validated instruments to assess ADHD are still unavailable in many languages other than English for teachers, which constitutes a clear obstacle to screening, diagnosis, and treatment of ADHD in many European countries. Method: Teachers rated 892 youths using the ADHD Rating Scale (ADHD-RS). We investigated the factor structure, reliability, and measurement invariance based on confirmatory factor analyses. Results: Results support a bifactor model, including one general ADHD factor and two specific Inattention and Hyperactivity-Impulsivity factors. But the latter is improperly defined calling into question the existence of a Predominantly Hyperactivity-Impulsivity subtype. The measurement invariance is fully supported across gender, age groups, and Gender × Age Groups. Conclusion: Results support the multiple-pathways hypothesis and suggest that a total ADHD score is meaningful, reliable, and valid, as well as specific assessments of Inattention. Some youths—especially older ones—may present a profile of ADHD particularly marked by Inattention symptoms. (J. of Att. Dis. 2016; 20(5) 434-444)
Biocompatibility and Inflammation Profile of B2A-Coated Granules Used in Arthrodesis
Authors: Zamora Paul O. , Liu Yi , Guo Henry , Lin Xinhua
Published: February 2013

The biocompatibility/inflammation profile of B2A-coated ceramic granules was evaluated using a panel of standard biocompatibility protocols (International Organization for Standardization-10993) including skin irritation and delayed-type hypersensitivity (Kligman maximization test), as well as acute, subacute, and chronic toxicity. Additionally, the potential of B2A-coated granules to elicit inflammatory reactions was also assessed using in vivo air pouch models, and B2A was evaluated using in vitro models of leukocyte recruitment and endothelial cell activation. Overall, the findings demonstrate that B2A-coated ceramic granules exhibit good biocompatibility profiles in the murine air pouch model and in standard subcutaneous implant models, and B2A did not demonstrate evidence of leukocyte recruitment or endothelial cell activation. These findings suggest that B2A and B2A-coated granules have little, if any, propensity to initiate inflammation reactions based on leukocyte recruitment. Thus, traditional biocompatibility and specially designed inflammation models indicate a high degree of biocompatibility and a low possibility of toxicity, inflammation, or edema following the implant of B2A-coated granules.
Learning to deploy (in)visibility: An examination of women leaders’ lived experiences
Authors: Stead Valerie
Published: February 2013

This article focuses on women’s learning from their lived experiences of leadership. In an examination of how six women leaders at a UK University learn to deploy (in)visibility, I draw on conceptualisations of (in)visibility more commonly found in feminist research. These include surface ideas of (in)visibility as states of exclusion or difference due to a lack of women in leadership roles, and deeper ideas of how states of visibility and invisibility are maintained through power relations. I also refer to ideas on how (in)visibility operates and is produced and reproduced through organisational processes and practices. This analysis extends critical perspectives of leadership learning and development. Specifically, it adds to understandings of the tacit nature of social and situated learning through an articulation of the ways in which gender and power operate in women’s learning of leadership from experiences of (in)visibility. This article concludes by indicating further areas for research, including more developed understandings of women’s learning to think strategically from experience, examining the role of management educators in revealing women’s leadership learning and identifying methodologies to examine women leaders’ learning experiences.
Developing leaders as symbolic violence: Reproducing public service leadership through the (misrecognized) development of leaders’ capitals
Authors: Tomlinson Michael , O’Reilly Dermot , Wallace Mike
Published: February 2013

A critical analysis is developed of the part that centrally initiated leadership development plays as a strategic lever for ensuring a steady supply of organizational leaders equipped and willing to meet the goals of widespread service improvement. Selected Bourdieusian conceptual tools are employed to illustrate how centrally initiated development of leaders operates as a form of ‘symbolic violence’: a covert means of perpetuating political elite domination. Organizational leaders misrecognize it as promoting their interest in expanding their influence because they are attracted by the opportunity it overtly offers to build their ‘capitals’. This process operates across two main administrative levels: the central (system) level and the organizational (local) level. The analysis is empirically grounded through the case of UK public services, drawing on a study of public service leaders, policymakers and representatives from national leadership development bodies in the United Kingdom. The findings illustrate how central policy elites endeavour to use leadership development to acculturate organizational leaders capable of responding favourably to a reconfigured and re-professionalized public service field. At the same time, organizational leaders consent to this through its perceived value in expanding their influence and developing their leader-related forms of capital.
Cooperative learning tasks in a Grade 6 intensive ESL class: Role of scaffolding
Authors: Gagné Nathalie , Parks Susan
Published: February 2013

Although a number of studies have investigated classroom-based peer interaction with adults and high school students, research pertaining to children in the elementary grades is scant. Drawing on sociocultural theory, the present study investigated how children in an intensive elementary level Grade 6 class for English as a second language (ESL) scaffolded each other while carrying out cooperative learning tasks. Interactions for two teams were analysed. As in the case of older learners, children were shown to be capable of engaging in linguistically oriented scaffolding. Although a variety of scaffolding strategies were in evidence, the two most frequently used pertained to request for assistance and other-correction. As in the Foster and Ohta (2005) study, the present analysis suggests that the strategies typically associated with negotiation of meaning within an interactionist perspective were rarely used. To explain how the children were orienting to the tasks, the importance of the classroom culture and the structure of the cooperative learning tasks were evoked.
An evaluation of questionnaires assessing physical activity levels in youth populations
Authors: Cancela Jose M , Ayán Carlos , Castro Antonio
Published: February 2013

The aim of this study was to revise and organize according to recall time based criteria, questionnaires created and validated to assess the level of physical activity in children and adolescents, with the intention of enabling their proper understanding and subsequent use by nurses and health care professionals. In order to determine the questionnaires’ quality, their degree of reliability and validity was the main feature to be taken into account. Thirty-eight papers were retrieved and analyzed, 31 of which were aimed at designing and validating a questionnaire intended for physical activity (PA) level assessment in youth populations (four to 19 year olds). The most widely used questionnaires were those whose recall time spans from one to seven days. In general, all questionnaires were characterized by the use of pen-and-paper format and scarce utilization of new technologies.

Based upon validity and reliability criteria, in order to assess PA level in children and adolescents, nurses should use the “Children’s Leisure Activities Study Survey” and the “Flemish Physical Activity Computer Questionnaire”, respectively. There is a need for the validation of these tools in other languages and cultures.
Asthma management self-efficacy in parents of primary school-age children
Authors: Brown Nicola , Gallagher Robyn , Fowler Cathrine , Wales Sandra
Published: February 2013

The aim of this study was to investigate asthma management self-efficacy in parents of primary school-age children with asthma and to explore possible associations between parent asthma management self-efficacy, parent and child characteristics, asthma task difficulty and asthma management responsibility. A cross-sectional descriptive survey of 113 parents was conducted to assess the level of parent asthma management self-efficacy, asthma task difficulty and confidence, asthma responsibility and socio-demographic characteristics. The findings indicate that parents had higher self-efficacy for attack prevention than attack management. Parents had higher self-efficacy for asthma management tasks that are simple, skills based and performed frequently such as medication administration and less confidence and greater difficulty with tasks associated with judgement and decision-making. Multivariate linear regression analysis identified English language, child asthma responsibility and parent education as predictors of higher asthma management self-efficacy, while an older child was associated with lower parent asthma management self-efficacy. The implications of these results for planning and targeting health education and self-management interventions for parents and children are discussed.
A reflective perspective on the challenges facing research-led teaching in the performing and creative arts
Authors: Walmsley Ben
Published: February 2013

This article provides a reflective perspective on the role that research-led teaching plays in the development of future arts workers in higher education. It explores the challenges faced by lecturers developing curricula in the performing and creative arts and argues that the increasing focus on employability can conflict with universities’ traditional aim of developing conceptual and critical thinkers. The article charges that the UK’s higher education sector is rapidly transforming itself into a two-tier system, which is serving to dichotomize vocational and academic learning even further. It concludes with a call for universities, students and employers to reject the false dichotomy between vocational and academic learning and perceive education in a more holistic, longitudinal sense, which might in turn develop more balanced graduates who excel in networked knowledge, conceptual and theoretical imagination and critical, lateral thinking.
The structure and properties of cellulose acetate materials: A comparative study on electrospun membranes and casted films
Authors: Wu Shaohua , Qin Xiaohong , Li Minxuan
Published: February 2013

Cellulose acetate (CA) membranes and films were fabricated, respectively, by electrospinning and solvent casting. A systematic analysis of structure and properties was made to compare the differences between nanotexture and casting texture. Scanning electron microscopy, X-ray diffraction and thermal analysis were used to characterize the morphology, inner structure and thermal behavior of electrospun CA membrane, casted CA film as well as original CA powder. In addition, the pore size distribution and surface hydrophilicity of electrospun membrane and casted film were tested. It was found that the nanotexture produced by electrospinning process had a significant effect on the structure and properties of CA materials. The pore size distribution of electrospun membrane was more uniform, although the mean pore size was larger. In addition, the electrospun CA membrane possessed higher crystallinity and better thermal stability, compared with casted CA film. The results also showed that the electrospun membrane gave a contact angle of 127.2° and was observably more hydrophobic than the casted film, reporting a contact angle of approximately 74.4°.
Toward Better Alzheimer’s Research Information Sources for the Public
Authors: Payne Perry W.
Published: February 2013

The National Plan to Address Alzheimer's Disease calls for a new relationship between researchers and members of the public. This relationship is one that provides research information to patients and allows patients to provide ideas to researchers. One way to describe it is a “bidirectional translational relationship.” Despite the numerous sources of online and offline information about Alzheimer's disease, there is no information source which currently provides this interaction. This article proposes the creation an Alzheimer's research information source dedicated to monitoring Alzheimer's research literature and providing user friendly, publicly accessible summaries of data written specifically for a lay audience. This information source should contain comprehensive, updated, user friendly, publicly available, reviews of Alzheimer's research and utilize existing online multimedia/social networking tools to provide information in useful formats that help patients, caregivers, and researchers learn rapidly from one another.
Acute calcium deposits in the hand and wrist; comparison of acute calcium peritendinitis and acute calcium periarthritis
Authors: Kim J. K. , Park E. S.
Published: February 2013

Acute calcium deposits are characterized by acute pain and a radiographic finding of amorphous calcification. A prospective, observational study was carried out on 30 consecutive patients undergoing conservative treatment for acute calcium deposits of the hand and wrist. Thirteen patients presented with acute calcific peritendinitis (Group A), and the other 17 with acute calcific periarthritis (Group B). All patients were followed for more than 12 months (mean 29 months). The average age at onset and recurrence rate of acute calcific peritendinitis were both significantly greater than for acute calcific periarthritis.
Every Study Begins With a Query
Authors: O’Brien Mary Jane , DeSisto Marie C.
Published: February 2013

School nurses have demonstrated a keen interest in research and the research process with the purpose of generating evidence that supports their practice and increases the value of school nursing services. This article will help school nurses to formulate research questions and to identify the components of the research question that delineate the next steps in the development of a research study from such questions. School nurses benefit from collaborating with experienced nurse researchers in order to gain competence in defining research questions.
Discrimination Across the Ideological Divide
Authors: Wetherell Geoffrey A. , Brandt Mark J. , Reyna Christine
Published: February 2013

Despite ample research linking conservatism to discrimination and liberalism to tolerance, both groups may discriminate. In two studies, we investigated whether conservatives and liberals support discrimination against value violators, and whether liberals’ and conservatives’ values distinctly affect discrimination. Results demonstrated that liberals and conservatives supported discrimination against ideologically dissimilar groups, an effect mediated by perceptions of value violations. Liberals were more likely than conservatives to espouse egalitarianism and universalism, which attenuated their discrimination; whereas the conservatives’ value of traditionalism predicted more discrimination, and their value of self-reliance predicted less discrimination. This suggests liberals and conservatives are equally likely to discriminate against value violators, but liberal values may ameliorate discrimination more than conservative values.
Contemporary Management of recurrent UTI in adult females
Authors: Christofides Angelos , Swallow Thomas , Parkinson Richard
Published: February 2013

The management of recurrent UTI is subject to significant variation and patients may fall under the care of a variety of specialties. We review the pathogenesis, investigation and management of this group of patients. Accurate diagnosis of UTI is the cornerstone of successful management, and careful interpretation of MSU results is needed. Although prophylactic antibiotic regimes are often successful, the emergence of antibiotic resistance mandates the cautious use of antibiotics and consideration of other initial therapies where possible.
Is the Pocket Ultrasound the “Phonendoscope” of the Urologist?
Authors: Pace Gianna , Carmignani Luca , Bozzini Giorgio , Picozzi Stefano , Lunelli Luca
Published: February 2013

The objective was to evaluate the utility of the “pocket ultrasound” in making clinical decisions in urologic emergencies. From May to September 2011, 105 patients were assessed for urologic emergencies: acute flank pain, macroscopic hematuria, urinary retention, and lower urinary tract symptoms. All patients underwent an ultrasonographic examination whereby the pocket ultrasound was used to evaluate the kidneys and bladder, followed by another appropriate diagnostic test to verify the suggested diagnosis. Urinary retention was diagnosed in 10 patients. Of 48 subjects with hematuria, 34 had an immediate diagnosis: there were 18 cases of a bladder tumor, 13 cases of urolithiasis, and 2 cases of renal cell carcinoma; one ureteral stent was detected. Of 30 patients referred with lower urinary tract symptoms, 14 showed a high post micturition residual and 2 were seen to have bladder diverticula. Of 17 patients with acute flank pain, 1 had a kidney abscess, 5 had hydronephrosis, and 11 had urolithiasis. Ultrasonography provided a conclusive diagnosis in 67.6% of cases. Point-of-care pocket ultrasound allows a rapid diagnosis for treatment or triage of patients for appropriate referral to other diagnostic methods.
Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia
Authors: Flanagan Jonathan M. , Sheehan Vivien , Linder Heidi , Howard Thad A. , Wang Yong-Dong , Hoppe Carolyn C. , Aygun Banu , Adams Robert J. , Neale Geoffrey A. , Ware Russell E.
Published: February 2013

Key Points

The complication of stroke is common in patients with SCA, and there is a genetic component. We have performed a large-association study to identify 2 genetic variants that protect patients with SCA from stroke.
Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans
Authors: Pieters Marlien , Kotze Retha C. , Jerling Johann C. , Kruger Annamarie , Ariëns Robert A. S.
Published: February 2013

Key Points

This paper describes the effect of fibrinogen γ′ on clot structure in plasma (previously shown in purified systems). This paper also describes the respective roles of total fibrinogen, fibrinogen γ′ concentration, and ratio on clot structure and lysis rates.
Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo
Authors: Hu Jingping , Liu Jing , Xue Fumin , Halverson Gregory , Reid Marion , Guo Anqi , Chen Lixiang , Raza Azra , Galili Naomi , Jaffray Julie , Lane Joseph , Chasis Joel Anne , Taylor Naomi , Mohandas Narla , An Xiuli
Published: February 2013

Key Points

Purification of staged human erythroblasts should facilitate a comprehensive cellular and molecular characterization of these cell populations. Quantification of human terminal erythropoiesis in vivo provides a powerful means for studying impaired erythropoiesis in human diseases.
Comparison of host cell gene expression in cowpox, monkeypox or vaccinia virus-infected cells reveals virus-specific regulation of immune response genes
Authors: Bourquain Daniel , Dabrowski Piotr Wojtek , Nitsche Andreas
Published: February 2013

Background

Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. The disease caused by each virus differs in terms of symptoms and severity, but little is yet know about the reasons for these varying phenotypes. They may be explained by the unique repertoire of immune and host cell modulating factors encoded by each virus. In this study, we analysed the specific modulation of the host cell’s gene expression profile by cowpox, monkeypox and vaccinia virus infection. We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells.

Results

Despite a dominating non-responsiveness of cellular transcription towards orthopoxvirus infection, we could identify several clusters of infection-modulated genes. These clusters are either commonly regulated by orthopoxvirus infection or are uniquely regulated by infection with a specific orthopoxvirus, with major differences being observed in immune response genes. Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection.

Conclusion

Despite their close genetic relationship, the expression profiles induced by infection with different orthopoxviruses vary significantly. It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species.
Viral-mediated expression of desmin mutants to create mouse models of myofibrillar myopathy
Authors: Joanne Pierre , Chourbagi Oussama , Hourdé Christophe , Ferry Arnaud , Butler-Browne Gillian , Vicart Patrick , Dumonceaux Julie , Agbulut Onnik
Published: February 2013

Background

The clinical features of myofibrillar myopathies display a wide phenotypic heterogeneity. To this date, no studies have evaluated this parameter due to the absence of pertinent animal models. By studying two mutants of desmin, which induce subtle phenotypic differences in patients, we address this issue using an animal model based on the use of adeno-associated virus (AAV) vectors carrying mutated desmin cDNA.

Methods

After preparation of the vectors, they were injected directly into the tibialis anterior muscles of C57BL/6 mice to allow expression of wild-type (WT) or mutated (R406W or E413K) desmin. Measurements of maximal force were carried out on the muscle in situ and then the injected muscles were analyzed to determine the structural consequences of the desmin mutations on muscle structure (microscopic observations, histology and immunohistochemistry).

Results

Injection of AAV carrying WT desmin results in the expression of exogenous desmin in 98% of the muscle fibers without any pathological or functional perturbations. Exogenous WT and endogenous desmin are co-localized and no differences were observed compared to non-injected muscle. Expression of desmin mutants in mouse muscles induce morphological changes of muscle fibers (irregular shape and size) and the appearance of desmin accumulations around the nuclei (for R406W) or in subsarcolemmal regions of fibers (for E413K). These accumulations seem to occur and disrupt the Z-line, and a strong regeneration was observed in muscle expressing the R406W desmin, which is not the case for E413K. Moreover, both mutants of desmin studied here induce a decrease in muscle force generation capacity.

Conclusions

In this study we show that AAV-mediated expression of desmin mutants in mouse muscles recapitulate the aggregation features, the decrease in contractile function and the morphological changes observed in patients with myofibrillar myopathy. More importantly, our results suggest that the R406W desmin mutant induces a robust muscle regeneration, which is not the case for the E413K mutant. This difference could help to explain the phenotypic differences observed in patients. Our results highlight the heterogeneous pathogenic mechanisms between different desmin mutants and open the way for new advances in the study of myofibrillar myopathies.
Limit State Strength of Unreinforced Masonry Structures
Authors: Akhaveissy A. H.
Published: February 2013

This paper presents a new formula to estimate the ultimate lateral force of unreinforced masonry structures. The ratio of the wall's height to the wall's width is used to predict the ultimate lateral load of the wall. The coefficient is determined by the numerical implementation of an interface model to simulate the behavior of mortar joints in masonry walls. The numerical predictions are compared with the FEMA guidelines and the experimental data. The comparisons show that the loads that are predicted by the proposed formula have a lower error percentage than the FEMA guidelines. Thus, the proposed formula can be used to analyze unreinforced masonry structures.
Prevalence of Off-Label Use and Spending in 2010 Among Patent-Protected Chemotherapies in a Population-Based Cohort of Medical Oncologists
Authors: Conti Rena M. , Bernstein Arielle C. , Villaflor Victoria M. , Schilsky Richard L. , Rosenthal Meredith B. , Bach Peter B.
Published: February 2013

Purpose

The prevalence of off-label anticancer drug use is not well characterized. The extent of off-label use is a policy concern because the clinical benefits of such use to patients may not outweigh costs or adverse health outcomes.

Methods

Prescribing data from IntrinsiQ Intellidose data systems, a pharmacy software provider maintaining a population-based cohort database of medical oncologists, was analyzed. Use of the most commonly prescribed anticancer drugs (“chemotherapies”) that were patent protected and administered intravenously to patients in 2010 was examined. Use was classified as “on-label” if the cancer site, stage, and therapy line met the US Food and Drug Administration (FDA)–approved indication. All other use was “off-label.” Off-label use was divided by whether it conformed to National Comprehensive Care Network (NCCN) Compendium recommendations, a basis of insurer coverage policies. IMS Health National Sales Perspectives was used to estimate national spending by use category.

Results

Ten chemotherapies met inclusion criteria. On-label use amounted to 70%, and off-label use amounted to 30%. Fourteen percent of use conformed to an NCCN-supported off-label indication, and 10% of off-label use was associated with an FDA-approved cancer site, but an NCCN-unsupported cancer stage and/or line of therapy. Total national spending on these chemotherapies amounted to $12 billion (B; $7.3B on-label, $2B off-label and NCCN supported; $2.5B off-label and NCCN unsupported).

Conclusion

Commonly used, novel chemotherapies are more often used on-label than off-label in contemporary practice. Off-label use is composed of a roughly equal mix of chemotherapy applied in clinical settings supported by the NCCN and those that are not.
Lack of Specificity of Plasma Concentrations of Inhibin B and Follicle-Stimulating Hormone for Identification of Azoospermic Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Green Daniel M. , Zhu Liang , Zhang Nan , Sklar Charles A. , Ke Raymond W. , Kutteh William H. , Klosky James L. , Spunt Sheri L. , Metzger Monika L. , Navid Fariba , Srivastava DeoKumar , Robison Leslie L. , Hudson Melissa M.
Published: February 2013

Purpose

Many male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain.

Patients and Methods

Semen analysis was performed and serum levels of FSH and inhibin B were measured in 275 adult male survivors of childhood cancer who had received gonadotoxic therapy. Receiver operating characteristic (ROC) analysis was performed to determine the optimal inhibin B and FSH values for identifying patients with azoospermia. The patient sample was divided into a learning set and a validation set. Sensitivity, specificity, and positive and negative predictive value were calculated.

Results

Inhibin B was dichotomized as ≤ 31 ng/L or more than 31 ng/L and FSH was dichotomized as ≤ 11.5 mIU/mL or more than 11.5 mIU/mL based on results of the ROC analysis. Using these values, the specificity of the serum level of inhibin B for identifying azoospermic survivors was 45.0%, and the positive predictive value was 52.1%. The specificity for FSH was 74.1%, and the positive predictive value was 65.1%.

Conclusion

Neither serum inhibin B nor FSH is a suitable surrogate for determination of sperm concentration in a semen sample. Young men and their physicians should be aware of the limitations of these measures for assessment of fertility potential.
Down-regulation of store-operated Ca2+ entry during mammalian meiosis is required for the egg-to-embryo transition
Authors: Lee Bora , Palermo Gianpiero , Machaca Khaled
Published: February 2013

A specialized Ca2+ transient at fertilization represents the universal driver for the egg-to-embryo transition. Ca2+ signaling remodels during oocyte maturation to endow the egg with the capacity to produce the specialized Ca2+ transient at fertilization, which takes the form of a single (e.g. Xenopus) or multiple (e.g. mouse) Ca2+ spikes depending on the species. Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx pathway in vertebrate oocytes, and in Xenopus SOCE completely inactivates during meiosis. Here we show that SOCE is down-regulated during mouse meiosis, but remains active in mature MII eggs. SOCE inhibition is due to a decreased ability of STIM1 to translocate to the cortical ER domain and due to internalization of Orai1. Reversing SOCE down-regulation by over-expressing STIM1 and Orai1 prolongs the Ca2+ oscillations at egg activation and disrupts the egg-to-embryo transition. Thus SOCE down-regulation during mammalian oocyte maturation is a critical determinant of the fertilization-specific Ca2+ transient, egg activation and early embryonic development.
Connexin30 mediated intercellular communication plays an essential role in epithelial repair in the cochlea
Authors: Forge Andrew , Jagger Daniel J. , Kelly John J. , Taylor Ruth R.
Published: February 2013

A role for connexin (Cx) 30 in epithelial repair following injury was examined in the organ of Corti, the sensory epithelium of the cochlea. In this tissue, lesions caused by loss of the sensory hair cells are closed by the supporting cells that surround each one. Gap junctions in which Cx30 is the predominant connexin are large and numerous between supporting cells. In mice carrying a deletion in the gene (Gjb6) that encodes Cx30, the size and number of gap junction plaques, and the extent of dye transfer, between supporting cells was greatly reduced compared with normal animals. This corresponded with unique peculiarities of the lesion closure events during the progressive hair cell loss that occurs in these animals in comparison with other models of hair cell loss whether acquired or as a result of a mutation. Only one, rather than all, of the supporting cells that contacted an individual dying hair closed the lesion, indicating disturbance of the co-ordination of cellular responses. The cell shape changes that the supporting cells normally undergo during repair of the organ of Corti did not occur, and there was disruption of the migratory activities that normally lead to the replacement of a columnar epithelium with a squamous-like one. These observations demonstrate a role for Cx30 and intercellular communication in regulating repair responses in an epithelial tissue.
Analysis of Methanobactin from Methylosinus Trichosporium OB3b via Ion Mobility Mass Spectrometry
Authors: Choi DongWon , Sesham Ramakrishna , Kim Yuri , Angel Laurence A.
Published: February 2013

Methanobactins (mbs) are low molecular mass copper binding chromopeptides analogous to pyoverdin class iron-binding siderophores. Mb produced by Methylosinus trichosporium OB3b (mb-OB3b) has been used as a model molecule for methanobactin although the amino acid sequence of mb-OB3b differs significantly from other characterized mbs. In particular, there is the presence of a pair of cystine residues which are absent in other characterized mbs. The role of the Cys3–Cys6 in copper binding, Cu(II) reduction and its role on the mb-OB3b structure remains in debate. Here, we use a single-step dithiothreitol treatment as an effective method in reducing the disulfide bond allowing in-depth ion mobility-mass spectrometry (IM-MS) analysis. The IM-MS results show mb-OB3b exists in the gas-phase as three different negatively-charged states and exists in multiple conformational states, when introduced via electrospray ionization from aqueous solution near physiological pH. The disulfide bond serves a structural role and is not involved in the Cu(I/II) binding capability of mb-OB3b, with the binding of a second Cu(I/II) related to a further deprotonation of mb-OB3b. Overall, these findings are in good correlation with expected solution-phase behavior of mb-OB3b. The results suggest IM-MS is an effective tool for better understanding the complex nature of this intriguing peptide.