bluuebunny/crossref_metadata_2025 huggingface dataset:
The rise of cancer in urban India: Cultural understandings, structural inequalities and the emergence of the clinic
Authors: Broom Alex , Doron Assa
Published: May 2011

Cancer services in India have evolved and expanded significantly in recent years, with a surge in the availability of biomedical oncological treatment facilities for certain cohorts of the Indian population in urban areas. Despite significant and sustained economic development in many areas of India, major issues persist in the delivery of cancer care, even in the context of relatively prosperous urban populations. This article explores the dilemmas evident in Indian cancer care as perceived by a group of Indian oncology clinicians. Specifically, the interviews focused on their perspectives on the key challenges facing cancer patients, particularly in relation to help-seeking and access to care. The main concerns that emerged in the interviews were: (a) practical constraint (i.e. access and treatment); (b) cultural values (i.e. communication, stigma and the clinic); and (c) structural conditions (i.e. inequalities related to place, gender and class). We unpack these as important elements of cancer care in contemporary India, and present Farmer’s notion of structural violence, among other concepts, as potentially useful for understanding some facets of this social problem. We conclude that without a greater understanding of social and cultural issues shaping cancer care in India, little progress will be made in coping with a disease that is set to become a major burden within an increasingly prosperous and ageing population.
The pursuit of medical knowledge and the potential consequences of the hidden curriculum
Authors: Michalec Barret
Published: May 2011

This study explores how preclinical medical students experience particular elements of their training, specifically their pursuit for medical knowledge and how this may impact their attributes as well as their relations with those outside of the realm of medicine. Ten first-year and 10 second-year students of a US medical school were interviewed regarding their experiences with and perceptions of their medical training. The students reported a cognitive and emotional distance from non-medical students that appears to be accentuated not only by their strenuous academic responsibilities but also elements of the hidden curriculum nested within medical training. Furthermore, students discuss experiencing disapproval, mistrust, and negative judgment toward laypersons thereby suggesting that this distancing may lend to deleterious effects on students’ ability and willingness to connect with others. A Parsonian lens is utilized to examine the notion of a ‘Knowledge Gap’ as well as aspects of the hidden curriculum in medical education and their role in professionalizing medical students.
Developing social work practice through engaging practitioners in action research
Authors: Fern Elizabeth
Published: May 2011

This article describes a particular approach – a methodology – for examining the ways in which social workers conceptualize children and childhood and the significance of this for developing social work practice. The research described was carried out in Iceland working directly with Icelandic social work practitioners. The methodology adopted used an action research approach, in which young people, who had interacted with social services, were engaged as research consultants. The article evaluates such an approach, paying particular attention to the approach as a method of generating new knowledge, and its usefulness for the development of social work practice.
‘It’s a tricky business!’: The impact of identity work in negotiating research access
Authors: Roesch-Marsh Autumn , Gadda Andressa , Smith Denise
Published: May 2011

The process of gaining research access in the social sciences is becoming increasingly difficult. Changes in legislation and an increasingly managerialist and risk-averse approach to service provision have contributed to organizations adopting a protectionist stance when it comes to granting research access. The student researcher’s experience of negotiating this research access landscape has been neglected. This article explores the findings from three case studies of gaining research access to social service organizations for the purpose of undertaking PhD research. It outlines the reflexive approach which was adopted, through peer support and discussion groups, in order to develop the ideas presented. The article utilizes emerging evidence, policy and identity theory to contextualize and develop understanding around the difficulties experienced in these three case studies. In particular the article highlights how issues of identity impact on the research access process. The article suggests strategies for gaining research access which could be adopted by student researchers, supervisors and universities. The article also recommends that issues to do with research governance and research access be considered in plans aimed at developing social work research capacity.
Speech–Language Pathologists’ Opinions on Response to Intervention
Authors: Sanger Dixie , Mohling Sara , Stremlau Aliza
Published: May 2011

The purpose of this study was to survey the opinions of speech–language pathologists (SLPs) on response to intervention (RTI). Questionnaires were mailed to 2,000 randomly selected elementary and secondary SLPs throughout the United States. Mean results of 583 respondents (29.15%) indicated that SLPs agreed on 37 Likert-type items and responded with neither agree nor disagree on 10 other items. The majority of participants acknowledged the importance of their role in RTI and the value of screening, progress monitoring, assessment, and prevention of continued failure. Some were uncertain whether multidisciplinary team members were knowledgeable and trained to implement RTI. More than 80% of participants indicated challenges related to training, funding, additional personnel, administrative leadership, and planning time. SLPs acknowledged the importance of prevention, collaboration, and well-trained educators in serving struggling learners. However, challenges in implementation of the model will require careful consideration in advancing the discussions on RTI.
Effects of Systemic Hydration on Vocal Acoustics of 18- to 35-Year-Old Females
Authors: Franca Maria Claudia , Simpson Kenneth O.
Published: May 2011

The influence of body hydration and vocal acoustics was investigated in this study. Effects of two levels of hydration on objective measures of vocal acoustics were explored. In an attempt to reduce variability in the degree of systemic hydration and to induce a state of systemic dehydration, participants were instructed to refrain from ingestion of food and liquids for 12 h prior to testing. Following the pretest (i.e., dehydration condition), each participant in the experimental group ingested 1 L of water within 20 min (i.e., rehydration condition). Vocal acoustics were collected at pretest and posttest by using vowel samples, which were then analyzed. Results related to the impact of the hydration condition on shimmer vocal acoustics averaging the 5 vowels for each subject in the analysis were found to have statistical significance, leading to the conclusion that the hydration condition had a positive impact on shimmer vocal acoustics.
Valerie Solanas and the Queer Performativity of Madness
Authors: Rowe Desireé D. , Chávez Karma R.
Published: May 2011

Accusations of madness have long been hurled at queer and feminist bodies, and typically when people are deemed mad, they are granted little agency. This article attempts to read madness as potentially agentic when it manifests as what we call a “queer performativity of madness.” Using the writing of and rhetoric surrounding Valerie Solanas, the infamous radical feminist known for shooting Andy Warhol, we develop the notion of a queer performativity of madness and show how historical figures like Solanas read against the binary oppositions that often create our understanding of sexuality, reason, and politics. Though madness does not always supply agency, we suggest that rethinking madness offers fruitful resources for feminist and queer theory.
The Role of Self-Efficacy Beliefs in Leader Development
Authors: Machida Moe , Schaubroeck John
Published: May 2011

This article examines various ways in which self-efficacy belief influences leader development. Drawing from social cognitive theory, we discuss four self-efficacy concepts that are pertinent to leader development: (a) preparatory self-efficacy, (b) efficacy spirals, (c) learning self-efficacy, and (d) resilient self-efficacy. We argue that the role of self-efficacy in leader development is more complex than traditionally considered. The article also addresses influences of a contextual factors and other individual differences on a leader’s self-efficacy. We then discuss the theoretical and practical implications of these propositions for leader development.
Trouble in Toms River
Authors: Lugg Catherine A. , Tooms Autumn K.
Published: May 2011

Drawing on a recent New Jersey Supreme Court decision (2007), this case addresses a school district’s responsibility regarding homophobic bullying, school culture, and the rights of lesbian, gay, bisexual, and transgender students to be free of discrimination.
Adding a low-dose antihypertensive regimen would substantially improve the control of hypertension and reduce cardiovascular morbidity among uncomplicated hypertensive patients
Authors: Ahola Teemu L , Kantola Ilkka M , Mäki Juhani , Reunanen Antti , Jula Antti M
Published: May 2011

Aims: To assess the utilization of antihypertensive drugs among uncomplicated hypertensive patients in Finland between 2000 and 2006 and to calculate the achievable reduction in cardiovascular morbidity, with intensified antihypertensive treatment. Methods: From the databases of the Social Insurance Institution of Finland, 428,986 treated hypertensives without diabetes or cardiac disease (further named uncomplicated hypertensives) in 2000 and 591,206 in 2006, respectively, were identified. In addition, from the Health 2000 survey representing the whole Finnish adult population, 729 uncomplicated hypertensives were determined to assess their characteristics and control of hypertension. Applying Law′s meta-analyses we calculated the reduction of blood pressure (BP) by intensifying the treatment with low-dose antihypertensive regimens for those with a BP ≥140/90 mmHg. Results: The nationwide data suggests a relative overuse of beta-blockers. Combination antihypertensive treatment increased relatively 8%, while at least three drug combinations increased from 19.8% to 21.6% between 2000 and 2006. However, calculated prevalence of controlled BP (<140/90 mmHg) increased only from 30.3% to 33.9%. Addition of one half standard dose or one to two half standard doses for the treatment of the patients with a BP ≥140/90 mmHg would improve the control of hypertension from 33.9% to 47.8% and 67.3%, respectively. The intensified treatment would reduce strokes by 18% and 28%, and ischaemic heart disease events by 13% and 21%, respectively. Conclusions: Underutilization of preferred drugs and poor control of BP continues. Surprisingly small addition of the number of low-dose antihypertensive regimen is needed in order to substantially improve the control of hypertension and to decrease cardiovascular morbidity among uncomplicated hypertensive patients.
Healthcare experiences of families affected by Huntington disease: need for improved care
Authors: Etchegary Holly
Published: May 2011

Objectives: To explore the healthcare experiences of families affected by Huntington disease (HD), a fatal neurodegenerative genetic disorder, and elicit their suggestions for improvement in the quality of care provided to them.

Methods: 24 semi-structured interviews were completed with members of families affected by HD in Eastern Canada. The sample was chosen to reflect a wide range of experiences with HD (e.g. patients, caregivers, family members at risk, but asymptomatic).

Results: Complex needs for healthcare services and emotional supports were found. Participants expressed frustration at the lack of knowledge about HD displayed by their family physicians. They described numerous difficulties accessing appropriate healthcare and other supports, and anticipated access difficulties in the future. Participants offered several suggestions to improve the quality of care to their families, including better education of healthcare professionals about the complex nature of HD and the provision of regular follow-up support.

Discussion: Health service planners and policy makers must recognize that HD is a debilitating, complicated illness requiring a high degree of care. Sustained follow-up support from knowledgeable healthcare professionals is required from the initial discovery of HD in the family, throughout a lengthy disease trajectory that normally ends with institutionalization.
Acrylamide Polymer Double-Network Hydrogels
Authors: Arnold Markus P. , Daniels Alma U. , Ronken Sarah , García Helena Ardura , Friederich Niklaus F. , Kurokawa Takayuki , Gong Jian P. , Wirz Dieter
Published: May 2011

Background:

In focal repair of joint cartilage and meniscus, initial stiffness and strength of repairs are generally much less than surrounding tissue. This increases early failure potential. Secure primary fixation of the repair material is also a problem. Acrylamide polymer double-network (DN) hydrogels are candidate-improved repair materials. DN gels have exceptional strength and toughness compared to ordinary gels. This stems from the double-network structure in which there is a high molar ratio of the second network to the first network, with the first network highly crosslinked and the second loosely crosslinked. Previous studies of acrylic PAMPS/PDMAAm and PAMPS/PAAm DN gels demonstrated physicochemical stability and tissue compatibility as well as the ability to foster cartilage formation.

Methods:

Mechanical properties related to surgical use were tested in 2 types of DN gels.

Results:

Remarkably, these >90%-water DN gels exhibited dynamic impact stiffness (E*) values (~1.1 and ~1.5 MPa) approaching swine meniscus (~2.9 MPa). Dynamic impact energy-absorbing capability was much lower (median loss angles of ~2°) than swine meniscus (>10°), but it is intriguing that >90%-water materials can efficiently store energy. Also, fine 4/0 suture tear-out strength approached cartilage (~2.1 and ~7.1 N v. ~13.5 N). Initial strength of attachment of DN gels to cartilage with acrylic tissue adhesive was also high (~0.20 and ~0.15 N/mm2).

Conclusions:

DN gel strength and toughness properties stem from optimized entanglement of the 2 network components. DN gels thus have obvious structural parallels with cartilaginous tissues, and their surgical handling properties make them ideal candidates for clinical use.
Modulation of TGF-β signaling by endoglin in murine hemangioblast development and primitive hematopoiesis
Authors: Zhang Liying , Magli Alessandro , Catanese Jacquelyn , Xu Zhaohui , Kyba Michael , Perlingeiro Rita C. R.
Published: May 2011

Endoglin (Eng), an accessory receptor for the transforming growth factor β (TGF-β) superfamily, is required for proper hemangioblast and primitive hematopoietic development. However the mechanism by which endoglin functions at this early developmental stage is currently unknown. Transcriptional analyses of differentiating eng−/− and eng+/+ ES cells revealed that lack of endoglin leads to profound reductions in the levels of key hematopoietic regulators, including Scl, Lmo2, and Gata2. We also detected lower levels of phosphorylated Smad1 (pSmad1), a downstream target signaling molecule associated with the TGF-β pathway. Using doxycycline-inducible ES cell lines, we interrogated the TGF-β signaling pathway by expressing activated forms of ALK-1 and ALK-5, type I receptors for TGF-β. Our results indicate that ALK-1 signaling promotes hemangioblast development and hematopoiesis, as evidenced by colony assays, gene expression and FACS analyses, whereas signaling by ALK-5 leads to the opposite effect, inhibition of hemangioblast and hematopoietic development. In Eng−/− ES cells, ALK-1 rescued both the defective hemangioblast development, and primitive erythropoiesis, indicating that ALK-1 signaling can compensate for the absence of endoglin. We propose that endoglin regulates primitive hematopoiesis by modulating the activity of the Smad1/5 signaling pathway in early stages of development.
Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow–derived mesenchymal stromal cells
Authors: Nwabo Kamdje Armel Hervé , Mosna Federico , Bifari Francesco , Lisi Veronica , Bassi Giulio , Malpeli Giorgio , Ricciardi Mario , Perbellini Omar , Scupoli Maria Teresa , Pizzolo Giovanni , Krampera Mauro
Published: May 2011

Although many literature data are available on the role of Notch signaling in T-cell acute lymphoblastic leukemia (ALL) biology, the importance of this molecular pathway in the development of B-lineage ALL (B-ALL) cells in the BM microenvironment is unknown so far. In this study, we used anti-Notch molecules neutralizing Abs and γ-secretase inhibitor (GSI) XII to investigate the role of the Notch signaling pathway in the promotion of human B-ALL cell survival in presence of stromal cell support. The treatment with combinations of anti-Notch molecule neutralizing Abs resulted in the decrease of B-ALL cell survival, either cultured alone or cocultured in presence of stromal cells from normal donors and B-ALL patients. Interestingly, the inhibition of Notch-3 and -4 or Jagged-1/-2 and DLL-1 resulted in a dramatic increase of apoptotic B-ALL cells by 3 days, similar to what is obtained by blocking all Notch signaling with the GSI XII. Our data suggest that the stromal cell–mediated antiapoptotic effect on B- ALL cells is mediated by Notch-3 and -4 or Jagged-1/-2 and DLL-1 in a synergistic manner.
SALL4 is a robust stimulator for the expansion of hematopoietic stem cells
Authors: Aguila Jerell R. , Liao Wenbin , Yang Jianchang , Avila Cecilia , Hagag Nabil , Senzel Lisa , Ma Yupo
Published: May 2011

HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The lack of donors and current inability to rapidly and efficiently expand HSCs are roadblocks in the development of successful cell therapies. Thus, the challenge of ex vivo human HSC expansion remains a fertile and critically important area of investigation. Here, we show that either SALL4A- or SALL4B-transduced human HSCs obtained from the mobilized peripheral blood are capable of rapid and efficient expansion ex vivo by >10 000-fold for both CD34+/CD38− and CD34+/CD38+ cells in the presence of appropriate cytokines. We found that these cells retained hematopoietic precursor cell immunophenotypes and morphology as well as normal in vitro or vivo potential for differentiation. The SALL4-mediated expansion was associated with enhanced stem cell engraftment and long-term repopulation capacity in vivo. Also, we demonstrated that constitutive expression of SALL4 inhibited granulocytic differentiation and permitted expansion of undifferentiated cells in 32D myeloid progenitors. Furthermore, a TAT-SALL4B fusion rapidly expanded CD34+ cells, and it is thus feasible to translate this study into the clinical setting. Our findings provide a new avenue for investigating mechanisms of stem cell self-renewal and achieving clinically significant expansion of human HSCs.
A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia
Authors: Perrot Aurore , Pionneau Cédric , Nadaud Sophie , Davi Frédéric , Leblond Véronique , Jacob Frédéric , Merle-Béral Hélène , Herbrecht Raoul , Béné Marie-Christine , Gribben John G. , Bahram Seiamak , Vallat Laurent
Published: May 2011

Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70− and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70+ and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70−) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease.
Normalization and centering of array-based heterologous genome hybridization based on divergent control probes
Authors: Darby Brian J , Jones Kenneth L , Wheeler David , Herman Michael A
Published: May 2011

Background

Hybridization of heterologous (non-specific) nucleic acids onto arrays designed for model-organisms has been proposed as a viable genomic resource for estimating sequence variation and gene expression in non-model organisms. However, conventional methods of normalization that assume equivalent distributions (such as quantile normalization) are inappropriate when applied to non-specific (heterologous) hybridization. We propose an algorithm for normalizing and centering intensity data from heterologous hybridization that makes no prior assumptions of distribution, reduces the false appearance of homology, and provides a way for researchers to confirm whether heterologous hybridization is suitable.

Results

Data are normalized by adjusting for Gibbs free energy binding, and centered by adjusting for the median of a common set of control probes assumed to be equivalently dissimilar for all species. This procedure was compared to existing approaches and found to be as successful as Loess normalization at detecting sequence variations (deletions) and even more successful than quantile normalization at reducing the accumulation of false positive probe matches between two related nematode species, Caenorhabditis elegans and C. briggsae. Despite the improvements, we still found that probe fluorescence intensity was too poorly correlated with sequence similarity to result in reliable detection of matching probe sequence.

Conclusions

Cross-species hybridizations can be a way to adapt genome-enabled tools for closely related non-model organisms, but data must be appropriately normalized and centered in a way that accommodates hybridization of nucleic acids with diverged sequence. For short, 25-mer probes, hybridization intensity alone may be insufficiently correlated with sequence similarity to allow reliable inference of homology at the probe level.
Exon sequence requirements for excision in vivo of the bacterial group II intron RmInt1
Authors: Barrientos-Durán Antonio , Chillón Isabel , Martínez-Abarca Francisco , Toro Nicolás
Published: May 2011

Background

Group II intron splicing proceeds through two sequential transesterification reactions in which the 5' and 3'-exons are joined together and the lariat intron is released. The intron-encoded protein (IEP) assists the splicing of the intron in vivo and remains bound to the excised intron lariat RNA in a ribonucleoprotein particle (RNP) that promotes intron mobility. Exon recognition occurs through base-pairing interactions between two guide sequences on the ribozyme domain dI known as EBS1 and EBS2 and two stretches of sequence known as IBS1 and IBS2 on the 5' exon, whereas the 3' exon is recognized through interaction with the sequence immediately upstream from EBS1 [(δ-δ' interaction (subgroup IIA)] or with a nucleotide [(EBS3-IBS3 interaction (subgroup IIB and IIC))] located in the coordination-loop of dI. The δ nucleotide is involved in base pairing with another intron residue (δ') in subgroup IIB introns and this interaction facilitates base pairing between the 5' exon and the intron.

Results

In this study, we investigated nucleotide requirements in the distal 5'- and 3' exon regions, EBS-IBS interactions and δ-δ' pairing for excision of the group IIB intron RmInt1 in vivo. We found that the EBS1-IBS1 interaction was required and sufficient for RmInt1 excision. In addition, we provide evidence for the occurrence of canonical δ-δ' pairing and its importance for the intron excision in vivo.

Conclusions

The excision in vivo of the RmInt1 intron is a favored process, with very few constraints for sequence recognition in both the 5' and 3'-exons. Our results contribute to understand how group II introns spread in nature, and might facilitate the use of RmInt1 in gene targeting.
Deficiency of maize starch-branching enzyme i results in altered starch fine structure, decreased digestibility and reduced coleoptile growth during germination
Authors: Xia Huan , Yandeau-Nelson Marna , Thompson Donald B , Guiltinan Mark J
Published: May 2011

Background

Two distinct starch branching enzyme (SBE) isoforms predate the divergence of monocots and dicots and have been conserved in plants since then. This strongly suggests that both SBEI and SBEII provide unique selective advantages to plants. However, no phenotype for the SBEI mutation, sbe1a, had been previously observed. To explore this incongruity the objective of the present work was to characterize functional and molecular phenotypes of both sbe1a and wild-type (Wt) in the W64A maize inbred line.

Results

Endosperm starch granules from the sbe1a mutant were more resistant to digestion by pancreatic α-amylase, and the sbe1a mutant starch had an altered branching pattern for amylopectin and amylose. When kernels were germinated, the sbe1a mutant was associated with shorter coleoptile length and higher residual starch content, suggesting that less efficient starch utilization may have impaired growth during germination.

Conclusions

The present report documents for the first time a molecular phenotype due to the absence of SBEI, and suggests strongly that it is associated with altered physiological function of the starch in vivo. We believe that these results provide a plausible rationale for the conservation of SBEI in plants in both monocots and dicots, as greater seedling vigor would provide an important survival advantage when resources are limited.
Spatial distribution of the risk of dengue fever in southeast Brazil, 2006-2007
Authors: Cordeiro Ricardo , Donalisio Maria R , Andrade Valmir R , Mafra Ana CN , Nucci Luciana B , Brown John C , Stephan Celso
Published: May 2011

Background

Many factors have been associated with circulation of the dengue fever virus and vector, although the dynamics of transmission are not yet fully understood. The aim of this work is to estimate the spatial distribution of the risk of dengue fever in an area of continuous dengue occurrence.

Methods

This is a spatial population-based case-control study that analyzed 538 cases and 727 controls in one district of the municipality of Campinas, São Paulo, Brazil, from 2006-2007, considering socio-demographic, ecological, case severity, and household infestation variables. Information was collected by in-home interviews and inspection of living conditions in and around the homes studied. Cases were classified as mild or severe according to clinical data, and they were compared with controls through a multinomial logistic model. A generalized additive model was used in order to include space in a non-parametric fashion with cubic smoothing splines.

Results

Variables associated with increased incidence of all dengue cases in the multiple binomial regression model were: higher larval density (odds ratio (OR) = 2.3 (95%CI: 2.0-2.7)), reports of mosquito bites during the day (OR = 1.8 (95%CI: 1.4-2.4)), the practice of water storage at home (OR = 2.5 (95%CI: 1.4, 4.3)), low frequency of garbage collection (OR = 2.6 (95%CI: 1.6-4.5)) and lack of basic sanitation (OR = 2.9 (95%CI: 1.8-4.9)). Staying at home during the day was protective against the disease (OR = 0.5 (95%CI: 0.3-0.6)). When cases were analyzed by categories (mild and severe) in the multinomial model, age and number of breeding sites more than 10 were significant only for the occurrence of severe cases (OR = 0.97, (95%CI: 0.96-0.99) and OR = 2.1 (95%CI: 1.2-3.5), respectively. Spatial distribution of risks of mild and severe dengue fever differed from each other in the 2006/2007 epidemic, in the study area.

Conclusions

Age and presence of more than 10 breeding sites were significant only for severe cases. Other predictors of mild and severe cases were similar in the multiple models. The analyses of multinomial models and spatial distribution maps of dengue fever probabilities suggest an area-specific epidemic with varying clinical and demographic characteristics.
Experience of violence and adverse reproductive health outcomes, HIV risks among mobile female sex workers in India
Authors: Swain Suvakanta N , Saggurti Niranjan , Battala Madhusudana , Verma Ravi K , Jain Anrudh K
Published: May 2011

Background

Female sex workers (FSWs) are a population sub-group most affected by the HIV epidemic in India and elsewhere. Despite research and programmatic attention to FSWs, little is known regarding sex workers' reproductive health and HIV risk in relation to their experiences of violence. This paper therefore aims to understand the linkages between violence and the reproductive health and HIV risks among a group of mobile FSWs in India.

Methods

Data are drawn from a cross-sectional behavioural survey conducted in 22 districts from four high HIV prevalence states (Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu) in India between September 2007 and July 2008. The survey sample included 5,498 FSWs who had moved to at least two different places for sex work in the past two years, and are classified as mobile FSWs in the current study. Analyses calculated the prevalence of past year experiences of violence; and adjusted logistic regression models examined the association between violence and reproductive health and HIV risks after controlling for background characteristics and program exposure.

Results

Approximately one-third of the total mobile FSWs (30.5%, n = 1,676) reported experiencing violence at least once in the past year; 11% reported experiencing physical violence, and 19.5% reported experiencing sexual violence. Results indicate that FSWs who had experienced any violence (physical or sexual) were significantly more likely to be vulnerable to both reproductive health and HIV risks. For example, FSWs who experienced violence were more likely than those who did not experience violence to have experienced a higher number of pregnancies (adjusted odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.0-1.6), ever experienced pregnancy loss (adjusted OR = 1.4, 95% CI = 1.2-1.6), ever experienced forced termination of pregnancy (adjusted OR = 2.4, 95% CI = 2.0-2.7), experienced multiple forced termination of pregnancies (adjusted OR = 2.2, 95% CI = 1.7-2.8), and practice inconsistent condom use currently (adjusted OR = 1.97, 95% CI: 1.4-2.0). Among FSWs who experienced violence, those who experienced sexual violence were more likely than those who had experienced physical violence to report inconsistent condom use (adjusted OR = 1.8, 95% CI: 1.4-2.3), and experience STI symptoms (adjusted OR = 1.3, 95% CI: 1.1-1.7).

Conclusion

The pervasiveness of violence and its association with reproductive health and HIV risk highlights that the abuse in general is an important determinant for reproductive health risks; and sexual violence is significantly associated with HIV risks among those who experienced violence. Existing community mobilization programs that have primarily focused on empowering FSWs should broaden their efforts to promote reproductive health in addition to the prevention of HIV among all FSWs, with particular emphasis on FSWs who experienced violence.
Cell-free synthesis of a functional G protein-coupled receptor complexed with nanometer scale bilayer discs
Authors: Yang Jian-Ping , Cirico Tatiana , Katzen Federico , Peterson Todd C , Kudlicki Wieslaw
Published: May 2011

Background

G protein coupled receptors (GPCRs) represent the largest family of membrane proteins in the human genome and the richest source of targets for the pharmaceutical industry. A major limitation to characterizing GPCRs has been the difficulty in developing high-level heterologous expression systems that are cost effective. Reasons for these difficulties include inefficient transport and insertion in the plasma membrane and cytotoxicity. Additionally, GPCR purification requires detergents, which have a negative effect on receptor yields and stability.

Results

Here we report a detergent-free cell-free protein expression-based method to obtain pharmacologically active GPCRs in about 2 hours. Our strategy relies on the co-translational insertion of modified GPCRs into nanometer-sized planar membranes. As a model we employed an engineered β2-adrenergic receptor in which the third intracellular loop has been replaced with T4 lysozyme (β2AR -T4L). We demonstrated that nanolipoprotein particles (NLPs) are necessary for expression of active β2AR -T4L in cell-free systems. The binding specificity of the NLP- β2AR-T4L complex has been determined by competitive assays. Our results demonstrate that β2AR-T4L synthesized in vitro depends on similar oxidative conditions as those required by an in vivo-expressed receptor.

Conclusions

Although the activation of β2AR-T4L requires the insertion of the T4 lysozyme sequence and the yield of that active protein limited, our results conceptually prove that cell-free protein expression could be used as a fast approach to express these valuable and notoriously difficult-to-express proteins.
Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes
Authors: Gibson Kyle R , Winterburn Tim J , Barrett Fiona , Sharma Sushma , MacRury Sandra M , Megson Ian L
Published: May 2011

Background

Platelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH). Clinical delivery ofN-acetylcysteine (NAC), a biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NACin vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes.

Methods

Blood samples (n= 13) were incubated (2 h, 37°C) with NAC (10-100 micromolar)in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry) was assessed, together with platelet GSH concentration (reduced and oxidized), antioxidant status, reactive oxygen species (ROS) generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO).

Results

At therapeutically relevant concentrations (10-100 micromolar), NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregationin vitro. Plasma NOx was enhanced by 30 micromolar NAC.

Conclusions

Our results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.
Prostate cancer metastases to the rectum: A case report
Authors: Abbas Tariq O , Al-Naimi Abdulla R , Yakoob Rafie A , Al-Bozom Issam A , Alobaidly Abdulkader M
Published: May 2011

Prostate cancer rarely metastasis to the rectum. Findings in the patient reported here emphasize the importance of the relationship between urinary and gastrointestinal symptoms in detecting prostatic neoplasms in older male patients.
SULFs in human neoplasia: implication as progression and prognosis factors
Authors: Bret Caroline , Moreaux Jérôme , Schved Jean-François , Hose Dirk , Klein Bernard
Published: May 2011

Background

The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within the heparan chains. Their action can modulate signaling processes, many of which with key relevance for cancer development and expansion. SULF1 has been associated with tumor suppressor effects in various models of cancer, whereas SULF2 dysregulation was in relation with protumorigenic actions. However, other observations argue for contradictory effects of these sulfatases in cancer, suggesting the complexity of their action in the tumor microenvironment.

Methods

We compared the expression of the genes encoding SULF1, SULF2 and heparan sulfate proteoglycans in a large panel of cancer samples to their normal tissue counterparts using publicly available gene expression data, including the data obtained from two cohorts of newly-diagnosed multiple myeloma patients, the Oncomine Cancer Microarray database, the Amazonia data base and the ITTACA database. We also analysed prognosis data in relation with these databases.

Results

We demonstrated that SULF2 expression in primary multiple myeloma cells was associated with a poor prognosis in two independent large cohorts of patients. It remained an independent predictor when considered together with conventional multiple myeloma prognosis factors. Besides, we observed an over-representation of SULF2 gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that SULF2 was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma.

We observed that, in addition to previous observations, SULF1 gene expression was increased in T prolymphocytic leukemia, acute myeloid leukemia and in renal carcinoma compared to corresponding normal tissues. Furthermore, we found that high SULF1 expression was associated with a poor prognosis in lung adenocarcinoma.

Finally, SULF1 and SULF2 were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers.

Conclusions

SULF1 and SULF2 are overexpressed in various human cancer types and can be associated to progression and prognosis. Targeting SULF1 and/or SULF2 could be interesting strategies to develop novel cancer therapies.
Evolutionary genomics of the pandemic 2009 H1N1 influenza viruses (pH1N 1v)
Authors: Qu Yanhua , Zhang Ruiying , Cui Peng , Song Gang , Duan Ziyuan , Lei Fumin
Published: May 2011

Background

A new strain of human H1N1 influenza A viruses was broken out in the April 2009 and caused worldwide pandemic emergency. The present study is trying to estimate a temporal reassortment history of 2009 H1N1 viruses by phylogenetic analysis based on a total 394 sequences of H1N1viruses isolated from swine, human and avian.

Results

Phylogenetic trees of eight gene segments showed that viruses sampled from human formed a well-supported clade, whereas swine and avian lineages were intermixed together. A new divergence swine sublineage containing gene segments of 2009 H1N1 viruses was characterized, which were closely related with swine viruses collected from USA and South Korea during 2004 to 2007 in six segments (PB2, PB1, PA, HA, NP and NS), and to swine viruses isolated from Thailand during 2004 to 2005 in NA and M. Substitution rates were varied drastically among eight segments and the average substitution rate was generally higher in 2009 H1N1 than in swine and human viruses (F

2

,23 = 5.972, P < 0.01). Similarly, higher d
N/d
S substitution ratios were identified in 2009 H1N1 than in swine and human viruses except M2 gene (F
2, 25 = 3.779, P < 0.05). The ages of 2009 H1N1 viruses were estimated around 0.1 to 0.5 year, while their common ancestors with closest related swine viruses existed between 9.3 and 17.37 years ago.

Conclusion

Our results implied that at least four reassortments or transmissions probably occurred before 2009 H1N1 viruses. Initial reassortment arose in 1976 and avian-like Eurasian swine viruses emerged. The second transmission happened in Asia and North America between 1988 and 1992, and mostly influenced six segments (PB2, PB1, PA, HA, NP and NS). The third reassortment occurred between North American swine and avian viruses during 1998 to 2000, which involved PB2 and PA segments. Recent reassortments occurred among avian-to-swine reassortant, Eurasian and classical swine viruses during 2004 to 2005. South Korea, Thailand and USA, were identified as locations where reassortments most likely happened. The co-circulation of multiple swine sublineages and special lifestyle in Asia might have facilitated mixing of diverse influenza viruses, leading to generate a novel virus strain.
Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer
Authors: Bae Sun Hyun , Park Won , Choi Doo Ho , Nam Heerim , Kang Won Ki , Park Young Suk , Park Joon Oh , Chun Ho Kyung , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol
Published: May 2011

Background

To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer.

Methods

From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy10 (14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT.

Results

Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy10 (p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05).

Conclusions

RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status.
Modularity-based credible prediction of disease genes and detection of disease subtypes on the phenotype-gene heterogeneous network
Authors: Yao Xin , Hao Han , Li Yanda , Li Shao
Published: May 2011

Background

Protein-protein interaction networks and phenotype similarity information have been synthesized together to discover novel disease-causing genes. Genetic or phenotypic similarities are manifested as certain modularity properties in a phenotype-gene heterogeneous network consisting of the phenotype-phenotype similarity network, protein-protein interaction network and gene-disease association network. However, the quantitative analysis of modularity in the heterogeneous network and its influence on disease-gene discovery are still unaddressed. Furthermore, the genetic correspondence of the disease subtypes can be identified by marking the genes and phenotypes in the phenotype-gene network. We present a novel network inference method to measure the network modularity, and in particular to suggest the subtypes of diseases based on the heterogeneous network.

Results

Based on a measure which is introduced to evaluate the closeness between two nodes in the phenotype-gene heterogeneous network, we developed a Hitting-Time-based method, CIPHER-HIT, for assessing the modularity of disease gene predictions and credibly prioritizing disease-causing genes, and then identifying the genetic modules corresponding to potential subtypes of the queried phenotype. The CIPHER-HIT is free to rely on any preset parameters. We found that when taking into account the modularity levels, the CIPHER-HIT method can significantly improve the performance of disease gene predictions, which demonstrates modularity is one of the key features for credible inference of disease genes on the phenotype-gene heterogeneous network. By applying the CIPHER-HIT to the subtype analysis of Breast cancer, we found that the prioritized genes can be divided into two sub-modules, one contains the members of the Fanconi anemia gene family, and the other contains a reported protein complex MRE11/RAD50/NBN.

Conclusions

The phenotype-gene heterogeneous network contains abundant information for not only disease genes discovery but also disease subtypes detection. The CIPHER-HIT method presented here is effective for network inference, particularly on credible prediction of disease genes and the subtype analysis of diseases, for example Breast cancer. This method provides a promising way to analyze heterogeneous biological networks, both globally and locally.
The Hannover experience: Surgical treatment of tongue cancer - A clinical retrospective evaluation over a 30 years period
Authors: Kokemueller Horst , Rana Majeed , Rublack Jennifer , Eckardt Andre , Tavassol Frank , Schumann Paul , Lindhorst Daniel , Ruecker Martin , Gellrich Nils-Claudius
Published: May 2011

Objectives

In this retrospective study, we present a clinical review of our experience with tongue cancer in order to obtain valid criteria for therapeutic decision-making.

Materials and methods

Between 1980 and 2009, a total of 341 patients with squamous cell carcinoma of the tongue were treated at our Department. The average follow-up was 5.2 years. 309 patients received surgical treatment, which was combined in nearly 10% with neoadjuvant and in nearly 20% with postoperative radio(chemo)therapy. 32 patients were excluded from surgery and received primary radiation.

Results

Local and regional failure occurred in 23.9% and 20.4%, leading to a total failure rate of 37.2% after an average duration of 1,6 years. N-Status, extracapsular spread and clear margins were identified as the dominant factors for survival, which was calculated with 54.5% after 5 years.

Conclusions

We recommend categorical bilateral neck dissection in order to reliably remove occult lymph node metastases. Adjuvant treatment modalities should be applied more frequently in controlled clinical trials and should generally be implemented in cases with unclear margins and lymphatic spread.

Clinical relevance

This study provides new treatment strategies for primary tumour disease and for tumour recurrence.