bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Two Sulfonphthalein Dyes for the Sensitive and Selective Extraction-Free Spectrophotometric Assay of Albendazole in Bulk Drug and in Tablets
Authors: Swamy Nagaraju , Basavaiah Kanakapura
Published: June 2013

Albendazole (ALB) is a potent benzimidazole anthelmintic used in the treatment of human intestinal helmintiasis as well as of hytatid cysts and neurocysticercosis. Two rapid, simple, sensitive, and selective spectrophotometric methods are presented for the determination of ALB in pharmaceuticals. The methods are based on the formation of dichloromethane soluble 1 : 1 ion-pair complexes (ALB : dye) formed between ALB and sulfonphthalein dyes, bromophenol blue BPB, (method A) and bromothymol blue BTB, (method B). The complexes formed were measured directly (without extraction) at 445 nm (method A) and 460 nm (method B). The experimental conditions were optimized and the systems obey Beer’s law for 1.5–21.0 and 2.0–32.0 μg mL−1 ALB for method A and method B respectively. The molar absorptivity and Sandell's sensitivity were calculated to be  L mol−1 cm−1 and 0.0209 ng cm−2, and  L mol−1 cm−1 and 0.0350 ng cm−2 using BPB and BTB, respectively. The limits of detection and quantification were calculated to be 0.01 and 0.03, and 0.16, and 0.49 μg mL−1 using BPB and BTB, respectively. The relative standard values for intra-day and inter-day precision were less than 3%, and the accuracy was better than 3% for both methods.
Significance of Kampo, Traditional Japanese Medicine, in Supportive Care of Cancer Patients
Authors: Yamakawa Jun-ichi , Motoo Yoshiharu , Moriya Junji , Ogawa Masao , Uenishi Hiroaki , Akazawa Sumiyo , Sasagawa Toshiyuki , Nishio Matomo , Kobayashi Junji
Published: June 2013

The current standard treatment for cancer is a multidisciplinary therapy whereby various types of treatment are properly combined. Chemotherapy with multiple anticancer drugs is now common, and traditional, complementary, and alternative therapies are adopted as supportive measures. Medical care in Japan is distinguished by the ability for patients to access both Western and Kampo medical cares at the same time. There is a high degree of trust in the safety of Kampo therapies because they are practiced by medical doctors who are educated with fundamental diagnosis of Western medicine. Highly reliable clinical studies are being published, demonstrating that palliative or supportive care for cancer patients using Kampo preparations alleviates adverse effects of chemotherapy or radiotherapy. This paper reports the circumstances around cancer care in Japan where traditional therapeutic Kampo formulas are used for patients undergoing cancer treatment with cutting-edge chemotherapy, specifically to alleviate adverse effects of anticancer drugs.
Systems of Navier-Stokes Equations on Cantor Sets
Authors: Yang Xiao-Jun , Baleanu Dumitru , Tenreiro Machado J. A.
Published: June 2013

We present systems of Navier-Stokes equations on Cantor sets, which are described by the local fractional vector calculus. It is shown that the results for Navier-Stokes equations in a fractal bounded domain are efficient and accurate for describing fluid flow in fractal media.
Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
Authors: Wiench Benjamin , Chen Yet-Ran , Paulsen Malte , Hamm Rebecca , Schröder Sven , Yang Ning-Sun , Efferth Thomas
Published: June 2013

Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb,Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three “-omics” assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.
An Expert System Based on Fisher Score and LS-SVM for Cardiac Arrhythmia Diagnosis
Authors: Yılmaz Ersen
Published: June 2013

An expert system having two stages is proposed for cardiac arrhythmia diagnosis. In the first stage, Fisher score is used for feature selection to reduce the feature space dimension of a data set. The second stage is classification stage in which least squares support vector machines classifier is performed by using the feature subset selected in the first stage to diagnose cardiac arrhythmia. Performance of the proposed expert system is evaluated by using an arrhythmia data set which is taken from UCI machine learning repository.
Stability of a Functional Differential System with a Finite Number of Delays
Authors: Rebenda Josef , Šmarda Zdeněk
Published: June 2013

The paper is devoted to the study of asymptotic properties of a real two-dimensional differential system with unbounded nonconstant delays. The sufficient conditions for the stability and asymptotic stability of solutions are given. Used methods are based on the transformation of the considered real system to one equation with complex-valued coefficients. Asymptotic properties are studied by means of Lyapunov-Krasovskii functional. The results generalize some previous ones, where the asymptotic properties for two-dimensional systems with one or more constant delays or one nonconstant delay were studied.
Efficient Semantics-Based Compliance Checking Using LTL Formulae and Unfolding
Authors: Song Liang , Wang Jianmin , Wen Lijie , Kong Hui
Published: June 2013

Business process models are required to be in line with frequently changing regulations, policies, and environments. In the field of intelligent modeling, organisations concern automated business process compliance checking as the manual verification is a time-consuming and inefficient work. There exist two key issues for business process compliance checking. One is the definition of a business process retrieval language that can be employed to capture the compliance rules, the other concerns efficient evaluation of these rules. Traditional syntax-based retrieval approaches cannot deal with various important requirements of compliance checking in practice. Although a retrieval language that is based on semantics can overcome the drawback of syntax-based ones, it suffers from the well-known state space explosion. In this paper, we define a semantics-based process model query language through simplifying a property specification pattern system without affecting its expressiveness. We use this language to capture semantics-based compliance rules and constraints. We also propose a feasible approach in such a way that the compliance checking will not suffer from the state space explosion as much as possible. A tool is implemented to evaluate the efficiency. An experiment conducted on three model collections illustrates that our technology is very efficient.
Inhibition of Protein Phosphatase 2A Radiosensitizes Pancreatic Cancers by Modulating CDC25C/CDK1 and Homologous Recombination Repair
Authors: Wei Dongping , Parsels Leslie A. , Karnak David , Davis Mary A. , Parsels Joshua D. , Marsh Amanda C. , Zhao Lili , Maybaum Jonathan , Lawrence Theodore S. , Sun Yi , Morgan Meredith A.
Published: June 2013

Purpose: To identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and thus improve survival, we conducted an siRNA library screen in pancreatic cancer cells. We investigated PPP2R1A, a scaffolding subunit of protein phosphatase 2A (PP2A) as a lead radiosensitizing target.

Experimental Design: We determined the effect of PP2A inhibition by genetic (PPP2R1A siRNA) and pharmacologic (LB100, a small molecule entering phase I clinical trials) approaches on radiosensitization of Panc-1 and MiaPaCa-2 pancreatic cancer cells both in vitro and in vivo.

Results: PPP2R1A depletion by siRNA radiosensitized Panc-1 and MiaPaCa-2 cells, with radiation enhancement ratios of 1.4 (P < 0.05). Likewise, LB100 produced similar radiosensitization in pancreatic cancer cells, but minimal radiosensitization in normal small intestinal cells. Mechanistically, PPP2R1A siRNA or LB100 caused aberrant CDK1 activation, likely resulting from accumulation of the active forms of PLK1 (pPLK1 T210) and CDC25C (pCDC25C T130). Furthermore, LB100 inhibited radiation-induced Rad51 focus formation and homologous recombination repair (HRR), ultimately leading to persistent radiation-induced DNA damage, as reflected by γ-H2AX expression. Finally, we identified CDC25C as a key PP2A substrate involved in LB100-mediated radiosensitization as depletion of CDC25C partially reversed LB100-mediated radiosensitization. In a mouse xenograft model of human pancreatic cancer, LB100 produced significant radiosensitization with minimal weight loss.

Conclusions: Collectively, our data show that PP2A inhibition radiosensitizes pancreatic cancer both in vitro and in vivo via activation of CDC25C/CDK1 and inhibition of HRR, and provide proof-of-concept evidence that PP2A is a promising target for the improvement of local therapy in pancreatic cancer. Clin Cancer Res; 19(16); 4422–32. ©2013 AACR.
Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer
Authors: Binder David C. , Engels Boris , Arina Ainhoa , Yu Ping , Slauch James M. , Fu Yang-Xin , Karrison Theodore , Burnette Byron , Idel Christian , Zhao Ming , Hoffman Robert M. , Munn David H. , Rowley Donald A. , Schreiber Hans
Published: June 2013

Immunogenic tumors grow progressively even when heavily infiltrated by CD8+ T cells. We investigated how to rescue CD8+ T-cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1+ tumor-specific CD8+ T cells that were dysfunctional. Treatment with αPD-L1– and αCTLA-4–blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using Salmonella Typhimurium A1-R (A1-R) to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8+ T-cell response: Proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8+ T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1-blocking antibody enhanced the expansion of tumor-specific CD8+ T cells and resulted in 80% tumor rejection. Collectively, these data show a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8+ T cells and eradicate advanced immunogenic tumors. Cancer Immunol Res; 1(2); 123–33. ©2013 AACR.
Chronische Bauchschmerzen: Psychosoziale Belastung und behandlungsinduzierte Veränderungen in der Krankheitsbewältigung
Authors: Groß Martina , Warschburger Petra
Published: June 2013

Hintergrund: Chronische Bauchschmerzen (CBS) sind im Kindesalter nicht nur weit verbreitet, sondern auch sehr stabil. Insbesondere psychosoziale Funktionseinschränkungen wie ein erhöhtes Stresserleben belasten die Kinder und deren Eltern und erschweren das Krankheitsmanagement; weitere komorbide Störungen können sich entwickeln. Dies legt nahe, dass eine Behandlung frühzeitig einsetzen und zudem auch die psychosozialen Aspekte mit berücksichtigen muss. Vor diesem Hintergrund wurde das kognitiv-behaviorale, kindzentrierte Gruppenprogramm «Stopp den Schmerz mit Happy-Pingu» entwickelt und evaluiert. Wie ist die psychosoziale Situation der betroffenen Kinder? Ist das kognitiv-behaviorale Programm in der Lage, psychosoziale Einschränkungen zu verbessern? Methodik: Das Programm besteht aus 6 Sitzungen für die Kinder sowie 1 Elternabend; die Trainingssitzungen fanden 1-mal wöchentlich statt. Im Rahmen einer randomisierten kontrollierten Studie wurde das Programm an 29 Kindern im Alter zwischen 6 und 12 Jahren auf seine Wirksamkeit hin überprüft. Die Evaluation erfolgte anhand eines Vergleiches zwischen Interventionsgruppe (IG) und Wartekontrollgruppe (WKG) zu den 3 Messzeitpunkten T1 (Prä), T2 (Post) und T3 (3-Monats-Follow-up). Ergebnisse: Bei den Kindern traten vor allem emotionale Probleme gehäuft auf. Die Akzeptanz des Programms war sehr hoch. Teilnehmer der IG erlebten im Vergleich zur WKG eine signifikante Verbesserung des Stresserlebens und der Coping-Strategien. Die Effektstärken sind überwiegend mittel bis hoch. Schlussfolgerungen: Multimodale kognitiv-behaviorale Ansätze scheinen geeignet, um Kinder mit CBS erfolgreich zu behandeln. Weitere kontrollierte Studien sollten unter anderem klären, welche Trainingselemente konkret für die Schmerzreduktion verantwortlich sind.
Carinomezium (Coleoptera: Ptinidae): A new genus from the Namaqualand region of South Africa
Authors: Wood Matthew V. , Philips T. Keith
Published: June 2013

A unique new genus and species of spider beetle from Namaqualand from the Succulent Karoo Biodiversity Hotspot in South Africa is described. The genus Carinomezium
gen. n. is characterized by pronounced longitudinal carinae on the elytra, four large rounded setal tufts that cover the pronotum, and the very small body size. The single representative species, Carinomezium namaquaensis
sp. n. is diagnosed, described, and illustrated. The phylogenetic placement of this taxon is also discussed.
A new species of Callianidea H. Milne Edwards, 1837 (Decapoda, Axiidea, Callianideidae) from the Pacific coast of Central America, with key to the genus
Authors: HERNÁEZ PATRICIO , VARGAS RITA
Published: June 2013

A new callianideid species, Callianidea mariamartae n. sp. is described from the Pacific coast of Costa Rica. The material is compared with the type description of C. laevicauda Gill, 1859 and C. typa H. Milne Edwards, 1837. Diagnostic features of the new species include a linea thalassinica very short, lateral margin of carapace with a distinct hepatic groove, accessory respiratory filaments unsegmented, outer uropodal ramus with strong longitudinal carinae. This is first record of the genus from eastern Pacific of Central America and third report of the family from world. A key for identification of the species belonging to the genus is provided in this document.
Impact of Misrepresentation of Freezing-Level Height by the TRMM Algorithm on Shallow Rain Statistics over India and Adjoining Oceans
Authors: Saikranthi K. , Rao T. Narayana , Radhakrishna B. , Bhaskara Rao S. Vijaya
Published: June 2013

The estimation of freezing level-height (FLH) by the Tropical Rainfall Measuring Mission (TRMM) algorithm is evaluated, against several other data sources, over India and adjoining oceans. It is observed that the TRMM algorithm either underestimates or overestimates the FLH [relative to radiosonde- and ECMWF Interim Re-Analysis (ERA)-derived FLH] at latitudes > 20°N over India. The agreement between the FLHs obtained from ERA and radiosonde and the TRMM-derived brightband height suggests that usage of ERA-derived FLH may improve shallow rain statistics. The impact of misrepresentation of FLH by the TRMM algorithm on shallow rain statistics is assessed by using 13 yr of TRMM precipitation radar measurements. It is noted that the misidentification of FLH alone affects (mostly underestimates) the shallow rain occurrence and rain fraction by 3%–8% over the study region. The magnitude of underestimation is large over the southern slopes of the Himalaya, the northern plains, and in northwestern India. TRMM identifies most of the shallow rain (30%–50%) as cold rain in regions where the underestimation of FLH is high. This situation could introduce some error in the correction of reflectivity for attenuation and in the retrieval of latent heat profiles.
Implicit–Explicit Runge–Kutta Methods for Fast–Slow Wave Problems
Authors: Whitaker Jeffrey S. , Kar Sajal K.
Published: June 2013

Linear multistage (Runge–Kutta) implicit–explicit (IMEX) time integration schemes for the time integration of fast-wave–slow-wave problems for which the fast wave has low amplitude and need not be accurately simulated are investigated. The authors focus on three-stage, second-order schemes and show that a scheme recently proposed by one of them (Kar) is unstable for purely oscillatory problems. The instability is reduced if the averaging inherent in the implicit part of the scheme is decentered, sacrificing second-order accuracy. Two alternative schemes are proposed with better stability properties for purely oscillatory problems. One of these utilizes a 3-cycle Lorenz scheme for the slow-wave terms and a trapezoidal scheme for the fast-wave terms. The other is a combination of two previously proposed schemes, which is stable for purely oscillatory problems for all fast-wave frequencies when the slow-wave frequency is less than a critical value. The alternative schemes are tested using a global spectral shallow-water model and a version of the NCEP operational global forecast model. The accuracy and stability of the alternative schemes are discussed, along with their computational efficiency.
The Sense of Earthiness: Everyday Aesthetics
Authors: Mandoki Katya
Published: June 2013

A lady, a mare, a lire and a vase are the examples chosen by Hippias Major to reply Socrates’ questions on beauty. These illustrate the fact that the debate on issues related to aesthetics began from the most concrete situations and basic items we may encounter day by day. In this paper I will consider two rudimentary events lacking any of the qualities traditionally considered aesthetic; items that have no elegance, grace or style and are not original, creative or expressive. These plain, simple objects and situations do not intend to incite contemplation because they do not conform to any model of art or beauty nor manifest syntactic or semantic complexity. I am referring to the most prosaic and yet capable of inducing a deep aesthetic response akin to that conveyed by traditional aesthetic objects. A difficult case to argue but for a quality which, despite being entirely ignored by western aesthetic theory, is still worth of regard. This quality may be defined as earthiness or the tellurian, a sensuous and symbolic celebration of sheer materiality in everyday life.
The development of Korea’s service industry from a global historical perspective
Authors: Phan Thanh Hoan , Jeong Ji Young
Published: June 2013

Korea’s economic structure has changed in a trend toward that of an advanced economy. Although the manufacturing sector has been dominating and a source of economic growth for a long period, there has been a recent shift toward the service industry. The sector’s share of both production output and employment is still rising. However, Korea’s service industry, despite its great significance in terms of employment and value-added, is not considered fully advanced. While its role is increasing, its economic share and rate of productivity growth is relatively slow compared with that of other countries. Thus, advancement of the service industry is essential in order to achieve a more prosperous economy. This paper presents the characteristics of Korea’s service industry and suggests strategies for its development.
Measuring the symptom burden associated with the treatment of chronic myeloid leukemia
Authors: Williams Loretta A. , Gonzalez Araceli G. Garcia , Ault Patricia , Mendoza Tito R. , Sailors Mary L. , Williams Janet L. , Huang Furong , Nazha Aziz , Kantarjian Hagop M. , Cleeland Charles S. , Cortes Jorge E.
Published: June 2013

Key Points

The MD Anderson Symptom Inventory for CML can be used to collect patient-reported symptoms for research and clinical practice. Thirty percent of patients in chronic-phase CML and on TKIs experience moderate symptoms that interfere with daily functioning.
Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI–measured liver iron content
Authors: Trottier Bryan J. , Burns Linda J. , DeFor Todd E. , Cooley Sarah , Majhail Navneet S.
Published: June 2013

Key Points

We found no association between iron overload and survival or complications in allogeneic transplant recipients at 1 year posttransplant. Future studies should use liver iron content to define iron overload instead of ferritin in this population.
An existence result for fractional differential inclusions with nonlinear integral boundary conditions
Authors: Ahmad Bashir , Ntouyas Sotiris K , Alsaedi Ahmed
Published: June 2013

This paper studies the existence of solutions for a fractional differential inclusion of order

q
∈
(
2
,
3
]

with nonlinear integral boundary conditions by applying Bohnenblust-Karlin’s fixed point theorem. Some examples are presented for the illustration of the main result.

MSC: 34A40, 34A12, 26A33.
Identification of nucleotides and amino acids that mediate the interaction between ribosomal protein L30 and the SECIS element
Authors: Bifano Abby L , Atassi Tarik , Ferrara Tracey , Driscoll Donna M
Published: June 2013

Background

Ribosomal protein L30 belongs to the L7Ae family of RNA-binding proteins, which recognize diverse targets. L30 binds to kink-turn motifs in the 28S ribosomal RNA, L30 pre-mRNA, and mature L30 mRNA. L30 has a noncanonical function as a component of the UGA recoding machinery that incorporates selenocysteine (Sec) into selenoproteins during translation. L30 binds to a putative kink-turn motif in the Sec Insertion Sequence (SECIS) element in the 3’ UTR of mammalian selenoprotein mRNAs. The SECIS also interacts with SECIS-binding protein 2 (SBP2), an essential factor for Sec incorporation. Previous studies showed that L30 and SBP2 compete for binding to the SECIS in vitro. The SBP2:SECIS interaction has been characterized but much less is known about how L30 recognizes the SECIS.

Results

Here we use enzymatic RNA footprinting to define the L30 binding site on the SECIS. Like SBP2, L30 protects nucleotides in the 5’ side of the internal loop, the 5’ side of the lower helix, and the SECIS core, including the GA tandem base pairs that are predicted to form a kink-turn. However, L30 has additional determinants for binding as it also protects nucleotides in the 3’ side of the internal loop, which are not protected by SBP2. In support of the competitive binding model, we found that purified L30 repressed UGA recoding in an in vitro translation system, and that this inhibition was rescued by SBP2. To define the amino acid requirements for SECIS-binding, site-specific mutations in L30 were generated based on published structural studies of this protein in a complex with its canonical target, the L30 pre-mRNA. We identified point mutations that selectively inhibited binding of L30 to the SECIS, to the L30 pre-mRNA, or both RNAs, suggesting that there are subtle differences in how L30 interacts with the two targets.

Conclusions

This study establishes that L30 and SBP2 bind to overlapping but non-identical sites on the SECIS. The amino acid requirements for the interaction of L30 with the SECIS differ from those that mediate binding to the L30 pre-mRNA. Our results provide insight into how L7Ae family members recognize their cognate RNAs.
Measuring effectiveness of the cervical cancer vaccine in an Australian setting (the VACCINE study)
Authors: Young Elisa J , Tabrizi Sepehr N , Brotherton Julia ML , Wark John D , Pyman Jan , Saville Marion , Wrede C David , Jayasinghe Yasmin , Tan Jeffrey , Gertig Dorota M , Pitts Marian , Garland Suzanne M
Published: June 2013

Background

The quadrivalent human papillomavirus vaccine has been provided in Australia through the National Human Papillomavirus Vaccination Program since April 2007. National registry data demonstrates good coverage of the vaccine, with 73% of school-aged girls having received all three doses. To evaluate the effectiveness of the program, we propose a two-pronged approach. In one (sub study A), the prevalence of the vaccine-targeted human papillomavirus genotypes in a population cohort is being estimated, and will be analysed in relation to vaccination status, cervical cytology screening status, demographic, social, behavioural, medical and clinical factors. In sub study B, the distribution of human papillomavirus genotypes detected in high grade cervical intraepithelial neoplastic lesions from vaccine eligible women is being assessed.

Methods/Design

Sub Study A involves the recruitment of 1569 women aged 18–25, residing in Victoria, Australia, through Facebook advertising. Women who are sexually active are being asked to provide a self-collected vaginal swab, collected at home and posted into the study centre, where human papillomavirus DNA detection and genotyping is performed. Participants also complete an online questionnaire regarding sexual history, experience with, knowledge of, and attitudes towards human papillomavirus, the human papillomavirus vaccine, and cervical screening.

Sub Study B will involve the collection of 500 cervical biopsies, positively identified as containing high grade cervical intraepithelial neoplastic lesions and/or adenocarcinoma in situ. Five serial sections are being taken from each case: sections 1 and 5 are being assessed to confirm the presence of the high grade cervical intraepithelial neoplastic lesions or adenocarcinoma in situ; human papillomavirus genotyping is performed on sections 2 and 3; single lesions are excised from section 4 using laser capture microdissection to specifically define causality of a human papillomavirus genotyping of each specific lesion.

Discussion

Australia is well placed to gain a clear and early insight into the effectiveness of the human papillomavirus vaccine in reducing the prevalence of human papillomavirus infection in young women, and any subsequent reduction in the prevalence of pre-cancerous cervical lesions, specifically high grade cervical intraepithelial neoplasia lesions, particularly of vaccine related types. The findings of a successful population based human papillomavirus program will have wide-reaching translational benefits across the globe.
Life experiences of patients who have completed tuberculosis treatment: a qualitative investigation in southeast Brazil
Authors: Dias Ana Angélica Lima , de Oliveira Daniela Maria Falcão , Turato Egberto Ribeiro , de Figueiredo Rosely Moralez
Published: June 2013

Background

Despite being curable, tuberculosis is still a stigmatized disease. Not only is TB patients’ suffering due to its clinical manifestations, but also because of society’s prejudice, embarrassing situations, and even self-discrimination. This study aims to investigate psychosocial experiences of patients who have completed tuberculosis treatment in São Carlos a municipality in the interior of São Paulo State, Brazil.

Methods

This study, of a clinical-qualitative nature, sought to understand the meanings provided by the participants themselves. Fifteen individuals, who had successfully completed tuberculosis treatment, participated in this research. The sample size was established using the information saturation criterion. Data were collected by means of interviews with in-depth open-ended questions. Data were treated by categorizing and analyzing content according to themes.

Results

Regardless of all progress, this study found that TB still causes patients to suffer from fear of transmission, social prejudice, and death. Despite the fact that the emotional support provided by families and healthcare professionals is considered essential to treatment adherence and completion, participants in this study reveal that friends and colleagues have distanced themselves from them for fear of contagion and/or prejudice. Ignorance about the disease and its transmission modes can be found in the interviewees’ statements, which seems to indicate that they have become vectors of transmission of stigma themselves. Patients’ medical leave from work during treatment may be due to both their health conditions and their attempt to avoid social/emotional embarrassment. There are accounts that TB has caused psychosocial damage to patients’ lives and that they feel more fatigue and lassitude and have begun to pay more attention to their own health.

Conclusions

Healthcare workers should be aware of the ways TB treatment affect patients’ psychosocial life and develop strategies to mitigate these effects and provide opportunities for them to share their anxiety, suffering, and bio-psychosocial changes. In addition, healthcare professionals should seek to educate and, as a result, empower TB patients and their families with regard to this disease so as to break the existing vicious cycle of misinformation and prejudice.
High frequency of the X-chromosome inactivation in young female patients with high-grade glioma
Authors: Li Gang , Zhang Zhiguo , Jin Tianbo , Liang Hongjuan , Tu Yanyang , Gong Li , Chen Zhongping , Gao Guodong
Published: June 2013

Background

Gliomas are common tumors and high-grade ones account for 62% of primary malignant brain tumors. Though current evidence have suggested that inherited risks play a role in glioma susceptibility, it was conveyed that glioma was such a complex disease, and the direct genetic contribution to glioma risk factors and its relation to other factors should be discussed more deeply. X-chromosome inactivation (XCI) is the mechanism by which gene dosage equivalence is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome. As skewed XCI has been linked to development of some solid tumors, including ovarian, breast, and pulmonary and esophageal carcinomas, it is challenging to elucidate the relation of skewed XCI to high-grade gliomas development.

Objective

The present study aimed to determine the general concordance between XCI pattern in blood cells and brain tissues, and SXCI frequencies in female patients with high-grade glioma compared to healthy controls.

Methods

1,103 Chinese females without a detectable tumor and 173 female high-grade glioma patients, were detected in the study. Normal brain tissues surrounding the lesions in gliomas were obtained from 49 patients among the 173 ones, with the microdissection using a laser microdissection microscope Genomic DNA was extracted from the peripheral blood cells and the normal brain tissues from the subjects. Exon 1 of androgen receptor (AR) gene was amplified, and its products of different alleles were resolved on denaturing polyacrylamide gels and visualized after silver staining. The corrected ratios (CR) of the products before and after Hpa II digestion were calculated.

Results

Occurrence of SXCI was detected in both the patients and controls at similar frequencies. However, the phenomenon, as defined as CR ≥ 3, was more frequent in the patients aging ≤40 (23.6%) compared to the corresponding reference group (5.1%, P <0.0001). When CR ≥ 10 was adopted, the frequencies were 5.5% and 1.6%, respectively. Their difference did not attain statistical significance (P = 0.10). When detected, both blood cells and brain tissue were compared after determination of a high concordance of XCI between blood cells and brain tissue collected from the same individuals (n = 48, r =0.57, P <0.01).

Conclusions

The data from the current study demonstrated that SXCI may be a predisposing factor for development of high-grade glioma in young female patients and further study will verify its suitability as a biomarker to assess susceptibility of young female patients to high-grade glioma.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935066233982578
Microarray gene expression profiling of neural tissues in bovine spastic paresis
Authors: Pariset Lorraine , Bongiorni Silvia , Bueno Susana , Gruber Cesare EM , Prosperini Gianluca , Chillemi Giovanni , Bicorgna Silvia , Gentile Arcangelo , Valentini Alessio
Published: June 2013

Background

Bovine Spastic Paresis (BSP) is a neuromuscular disorder which affects both male and female cattle. BSP is characterized by spastic contraction and overextension of the gastrocnemious muscle of one or both limbs and is associated with a scarce increase in body weight. This disease seems to be caused by an autosomal and recessive gene, with incomplete penetration, although no genes clearly involved with its onset have been so far identified. We employed cDNA microarrays to identify metabolic pathways affected by BSP in Romagnola cattle breed. Investigation of those pathways at the genome level can help to understand this disease.

Results

Microarray analysis of control and affected individuals resulted in 268 differentially expressed genes. These genes were subjected to KEGG pathway functional clustering analysis, revealing that they are predominantly involved in Cell Communication, Signalling Molecules and Interaction and Signal Transduction, Diseases and Nervous System classes. Significantly enriched KEGG pathway’s classes for the differentially expressed genes were calculated; interestingly, all those significantly under-expressed in the affected samples are included in Neurodegenerative Diseases. To identify genome locations possibly harbouring gene(s) involved in the disease, the chromosome distribution of the differentially expressed genes was also investigated.

Conclusions

The cDNA microarray we used in this study contains a brain library and, even if carrying an incomplete transcriptome representation, it has proven to be a valuable tool allowing us to add useful and new information to a poorly studied disease. By using this tool, we examined nearly 15000 transcripts and analysed gene pathways affected by the disease. Particularly, our data suggest also a defective glycinergic synaptic transmission in the development of the disease and an alteration of calcium signalling proteins. We provide data to acquire knowledge of a genetic disease for which literature still presents poor results and that could be further and specifically analysed in the next future. Moreover this study, performed in livestock, may also harbour molecular information useful for understanding human diseases.
Factors Associated With Hearing Impairment in Patients With Congenital Hypothyroidism Treated Since the Neonatal Period: A National Population-Based Study
Authors: Lichtenberger-Geslin Lydia , Dos Santos Sophie , Hassani Yasmine , Ecosse Emmanuel , Van Den Abbeele Thierry , Léger Juliane
Published: June 2013

Context:

Untreated hypothyroidism is known to impair hearing, but little is known about the long-term hearing of patients treated for congenital hypothyroidism (CH) since the neonatal period.

Objective:

The purpose of this study was to assess hearing and its determinants in a population-based registry of young adult patients with CH.

Design, Setting, and Participants:

Self-declared hearing loss was evaluated in 1202 of the 1748 eligible patients with CH who completed a questionnaire on health status at a median age of 23.4 years. Audiograms were obtained for one third of the patients declaring hearing loss (37 of 107).

Main Outcome Measures:

Self-declared hearing loss and audiogram characteristics for patients reporting hearing impairment were measured.

Results:

These patients had a risk of self-declared hearing loss more than 3 times higher than that for the reference population (relative risk [RR] = 3.7; 95% confidence interval [CI], 2.9–4.7). Hearing impairment was diagnosed at a median age of 7.0 (25th–75th percentiles, 3.4–19.0) years, and 17% of affected patients required hearing support in early adulthood. Hearing loss was associated with the type of CH (patients with athyreosis and gland in situ were more frequently affected than those with an ectopic gland [RR = 2.61; 95% CI, 1.77–3.88]), with disease severity, as assessed by bone maturation delay at the time of diagnosis, with at least one knee epiphyseal ossification center absent in the most severe form (RR = 2.29; 95% CI, 1.39–3.79), and with other associated chronic diseases (RR = 3.64; 95% CI, 2.35–5.62). A trend for association with serum free T4 concentration at diagnosis was also observed (RR = 1.47; 95% CI, 0.96–2.23). Hearing loss was mostly bilateral (90%), mild to moderate (96%), of the sensorineural type (76%), and concerned high or very high frequencies.

Conclusion:

Despite major improvements in prognosis, hearing loss remains a significant problem, particularly in patients with severe CH. Parents and primary care providers should be aware of this risk, because early diagnosis and intervention could improve the long-term prognosis in these patients.
Transfer of polyglutamine aggregates in neuronal cells occurs in tunneling nanotubes
Authors: Costanzo Maddalena , Abounit Saïda , Marzo Ludovica , Danckaert Anne , Chamoun Zeina , Roux Pascal , Zurzolo Chiara
Published: June 2013

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by CAG expansion in the huntingtin gene, which adds a homopolymeric tract of polyglutamine (polyQ) to the encoded protein leading to the formation of toxic aggregates. Despite rapidly accumulating evidences supporting a role for intercellular transmission of protein aggregates, little is known about whether and how huntingtin (Htt) misfolding progresses through the brain. It has been recently reported that synthetic polyQ peptides and recombinant fragments of mutant Htt are readily internalized in cell cultures and able to seed polymerization of a reporter wild-type Htt. However there is no direct evidence of aggregate transfer between cells and the mechanism has not been explored. By expressing recombinant fragments of mutant Htt in neuronal cells and in primary neurons, here we show that aggregated fragments formed within one cell spontaneously transfer to neighbors in cell culture. We demonstrate that aggregates intercellular spreading requires cell-cell contact and does not occur upon aggregates secretion. Interestingly, we report that the expression of mutant, but not wild-type Htt fragments, increases the number of tunneling nanotubes (TNTs), which in turn provide an efficient mechanism of transfer.
TGFβ receptor I transactivation mediates stretch-induced Pak1 activation and CTGF upregulation in mesangial cells
Authors: Chen G. , Chen X. , Sukumar A. , Gao B. , Curley J. , Schnaper H. W. , Ingram A. J. , Krepinsky J. C.
Published: June 2013

Increased intraglomerular pressure is an important pathogenic determinant of kidney fibrosis in the progression of chronic kidney disease, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical stretch. MC produce extracellular matrix and profibrotic cytokines, including connective tissue growth factor (CTGF) when exposed to stretch. We show that p21-activated kinase 1 (Pak1) is activated by stretch in MC and in vivo in a model marked by elevated intraglomerular pressures. Its activation is essential for CTGF upregulation. Rac1 is an upstream regulator of Pak1 activation. Stretch induces transactivation of the type I transforming growth factor β1 receptor (TβRI) independently of ligand binding. TβRI transactivation is required not only for Rac1/Pak1 activation, but also leads to activation of the canonical TGFβ signaling intermediate Smad3. We show that Smad3 activation is an essential requirement for CTGF upregulation in MC under mechanical stress. Pak1 regulates Smad3 C-terminal phosphorylation and transcriptional activation. However, a second signaling pathway, that of RhoA/Rho-kinase and downstream Erk activation, is also required for stretch-induced CTGF upregulation in MC. Importantly, this is also regulated by Pak1. Thus, Pak1 serves as a novel central mediator in the stretch-induced upregulation of CTGF in MC.
Finite Element Analysis of the Dynamic Response of Composite Floors Subjected to Walking Induced Vibrations
Authors: Behnia Arash , Chai Hwa Kian , Ranjbar Navid , Behnia Nima
Published: June 2013

The applications of composite materials have been widely practiced in modern construction. Structural engineers are often urged to consider aesthetic values as well as the financial aspects in their work, which results in structures that have long span, lightweight and low natural frequencies. These structures exhibit excessive vibrations that cause major discomforts to the occupants. The purpose of this study is to establish a methodology using finite element analysis for assessing the dynamic responses of composite floors and determining the corresponding level of comfort. Linear elastic finite element analysis was conducted using more realistic load models with respect to the application of different geometries of concrete slab and fiber reinforced polymer materials. The composite floor investigated included FRP deck, FRP beams, and concrete slabs of various thicknesses. The resulting maximum peak accelerations indicated the need for more realistic load models to generate a time function including space, time and heel impact descriptions. The FRP deck or beam was satisfactory in terms of serviceability and comfort level. There were no significant differences between the results when fiber reinforced polymer materials or common concrete-steel composite floors were used.
Culture Change in a Professional Sports Team: Shaping Environmental Contexts and Regulating Power
Authors: Cruickshank Andrew , Collins Dave , Minten Sue
Published: June 2013

Although high performing cultures are crucial for the enduring success of professional sport performance teams, theoretical and practical understanding of how they are established and sustained is lacking. To develop knowledge in this area, a case study was undertaken to examine the key mechanisms and processes of a successful culture change programme at English Rugby Union's Leeds Carnegie. Exploring the change process from a 360 degree perspective, semi-structured interviews were conducted with team management, one specialist coach, six players, and the CEO. Analysed and explained through decentred theory, results revealed that culture change was effectively facilitated by team management: A) subtly and covertly shaping the physical, structural, and psychosocial context in which support staff and players made performance-impacting choices, and b) regulating the ‘to and fro’ of power which characterises professional sport performance teams. Decentred theory is also supported as an effective framework for culture change study.
Three-Dimensional Kinematics during the Take-Off Phase in Competitive Long Jumping
Authors: Campos José , Gàmez Javier , Encarnación Alberto , Gutiérrez-Dávila Marcos , Rojas Javier , Wallace Eric S
Published: June 2013

The purpose of the present study was to identify the relationships among selected kinematic variables that affect the take-off phase and performance in elite jumpers. The jump distance was found to be related to: I) the athlete's approach speed before the instant of touch down; and ii) the exchange in spatial velocity components at take-off, which results in a gain in maximum vertical velocity of the centre of mass (CM), favoured by the use of an optimum touch-down angle of the take-off leg, an active landing of the foot at touch-down, and a motion of the take-off leg during the compression phase that helps to manage the loss of horizontal velocity. Nonetheless, the results show that an adequate velocity transformation requires an adaptive technical model to help jumpers to build an efficient individual technical pattern.
Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy
Authors: Paylor Ben , Fernandes Justin , McManus Bruce , Rossi Fabio
Published: June 2013

Arrhythmogenic cardiomyopathy (AC) is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.
Bridging the Gap: Clinical Practice Nursing and the Effect of Role Strain on Successful Role Transition and Intent to Stay in Academia
Authors: Cranford Joan S.
Published: June 2013

The shortage of registered nurses is inextricably linked to the shortage of nursing faculty which has resulted in the turning away of over 40,000 qualified students in 2010. One solution to the faculty shortage has been to recruit faculty from clinical practice. This often becomes problematic resulting in intent to leave academia within five years. Possible factors contributing to this action are role ambiguity and role strain. This study, therefore, examined role strain experienced by nursing faculty and the extent to which role strain predicted satisfaction with the role transition and intent to stay in academia. Findings revealed that role strain does exist among nursing faculty. Role ambiguity and self-assessed competency are significant predictors of role strain, and role strain is a significant predictor of satisfaction with the role transition and intent to stay. The study also looked at whether age, education, and experience affected role strain, and they were found to be poor predictors.
Resisting, Reaching Out and Re-imagining to Independence: LPN’s Transitioning towards BNs and Beyond
Authors: Melrose Sherri , Wishart Paul M.
Published: June 2013

Little is known about the process of how nurses transition between vocational training and institutions of higher education. Understanding this process provides educators with the knowledge to support new groups of university students making this transition. Grounded theory (GT) was used to explore and understand this process. Three studies from a 7-year research program were used as data. The analysis led to the generation of a GT illuminating the process of students transitioning from post-LPN to BN. This GT illustrates how students overcome difficulties encountered moving to a more complex nursing role. The students’ main concern was a lack of independence. The core variable, which resolves this main concern, and which emerged from the analysis of the data is developing independence. There are three sub-core variables, resisting, reaching out and re-imagining which support this core variable of developing independence.