bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Reasoning and Decision Making in the Context of Health Information Technology
Authors: Patel Vimla L. , Kaufman David R. , Kannampallil Thomas G.
Published: September 2013

Diagnostic reasoning and medical decision making have been focal areas of research in the fields of medical education, cognition, and artificial intelligence in medicine. Drawing on several decades worth of research, we propose an integrated summary of prior research on diagnostic reasoning and decision making—in terms of both historical development and theoretical shifts. We also characterize the changes in research and theory resulting from the incorporation and adoption of health information technology in the clinical work place. In this paper, we differentiate between the various forms of diagnostic reasoning and trace the evolution of the various models of reasoning, including knowledge-based, exemplar-based, and visual strategies. We also discuss the effect of clinical expertise on reasoning processes. Within the medical decision-making research, we delineate the various approaches highlighting decision-making errors that arise due to the nature of heuristics and biases and other factors. Although there has been significant progress in our understanding, there is still a need for greater theoretical integration of disparate empirical phenomena. Specifically, there is a need to reconcile the various characterizations of reasoning and to evaluate the similarity and differences in the context of current health care practice. Finally, we discuss the role of human factors research in the study of clinical environments and also in relation to devising approaches and methodologies for understanding, evaluating, and supporting the diagnostic reasoning and decision processes.
Communicating Numerical Risk
Authors: Brust-Renck Priscila G. , Royer Caisa E. , Reyna Valerie F.
Published: September 2013

In this chapter, we review evidence from the human factors literature that verbal and visual formats can help increase the understanding of numerical risk information in health care. These visual representations of risk are grounded in empirically supported theory. As background, we first review research showing that people often have difficulty understanding numerical risks and benefits in health information. In particular, we discuss how understanding the meanings of numbers results in healthier decisions. Then, we discuss the processes that determine how communication of numerical risks can enhance (or degrade) health judgments and decisions. Specifically, we examine two different approaches to risk communication: a traditional approach and fuzzy-trace theory. Applying research on the complications of understanding and communicating risks, we then highlight how different visual representations are best suited to communicating different risk messages (i.e., their gist). In particular, we review verbal and visual messages that highlight gist representations that can better communicate health information and improve informed decision making. This discussion is informed by human factors theories and methods, which involve the study of how to maximize the interaction between humans and the tools they use. Finally, we present implications and recommendations for future research on human factors in health care.
Teamwork and Collaboration
Authors: Xiao Yan , Parker Sarah Henrickson , Manser Tanja
Published: September 2013

Safety and quality of health care depend on collaborative efforts of multiprofessional and multidisciplinary teams of care providers. Team research in aviation and the military has produced a wealth of knowledge in terms of concepts and intervention strategies to improve team performance. Research on collaborative work in health care in the past 20 years has uncovered unique characteristics and requirements of teams in hospitals and other health care settings and has provided early assessment of the utility of the theoretical concepts, methodologies, and interventions developed outside health care. In this chapter, we review a set of concepts that have been used in characterizing teams in health care and in improving teamwork. These concepts include the organizational shell to capture the sociotechnical environment in which teams reside as well as nontechnical skills, team leadership, team mental models, and so on. We will review a number of leading interventions to enhance team performance, such as teamwork training (e.g., TeamSTEPPS) and structured communication (e.g., SBAR). Future directions are suggested on better understanding of the interdependencies between teams and their organizational shell, such as standardization of operating procedures and training, and to focus on the patient in terms of teamwork improvement.
Collaborative Cardiovascular Risk Reduction in Primary Care II (CCARP II)
Authors: Yakiwchuk Erin M. , Jorgenson Derek , Mansell Kerry , Laubscher Tessa , LeBras Marlys , Blackburn David F.
Published: September 2013

Background:

Previous pharmacist interventions to reduce cardiovascular (CV) risk have been limited by low patient enrolment. The primary aim of this study was to implement a collaborative pharmacist intervention that used a systematic case-finding procedure to identify and manage patients with uncontrolled CV risk factors.

Methods:

This was an uncontrolled, program implementation study. We implemented a collaborative pharmacist intervention in a primary care clinic. All adults presenting for an appointment with a participating physician were systematically screened and assessed for CV risk factor control by the pharmacist. Recommendations for risk factor management were communicated on a standardized form, and the level of pharmacist follow-up was determined on a case-by-case basis. We recorded the proportion of adults exhibiting a moderate to high Framingham risk score and at least 1 uncontrolled risk factor. In addition, we assessed before-after changes in CV risk factors.

Results:

Of the 566 patients who were screened prior to visiting a participating physician, 186 (32.9%) exhibited moderate or high CV risk along with at least 1 uncontrolled risk factor. Physicians requested pharmacist follow-up for 60.8% (113/186) of these patients. Of the patients receiving the pharmacist intervention, 65.5% (74/113) were at least 50% closer to 1 or more of their risk factor targets by the end of the study period. Significant risk factor improvements from baseline were also observed.

Discussion:

Through implementation of a systematic case-finding approach that was carried out by the pharmacist on behalf of the clinic team, a large number of patients with uncontrolled risk factors were identified, assessed and managed with a collaborative intervention.

Conclusion:

Systematic case finding appears to be an important part of a successful intervention to identify and manage individuals exhibiting uncontrolled CV risk factors in a primary care setting.
Apartheid or Not Apartheid? The Russell Tribunal on Palestine, South Africa Session, November 2011
Authors: Harlow Barbara
Published: September 2013

Apartheid or not apartheid?: that was the question addressed by participants – both jurors and expert witnesses – in the third session of the Russell Tribunal on Palestine over the course of its deliberations in Cape Town, South Africa, from the 5th to the 7th of November, 2011. Specifically, that is, the tribunal adherents were concerned to learn “whether Israel’s policy and certain practices affecting the Palestinian population in Israeli territory and the Palestinian territories occupied by Israel” could be taken to have (1) “amount(ed) to a ‘breach on the international legal prohibition of apartheid,’” and/or (2) did these policies and practices “constitute persecution as a crime against humanity”? This article discusses some of the contributions to that discussion, the competing political and humanitarian stakes, and the vexed comparisons/contrasts between apartheid South Africa and Israel.
Red clover causing symptoms suggestive of methotrexate toxicity in a patient on high-dose methotrexate
Authors: Orr Ancel , Parker Rachel
Published: September 2013

The case report discusses a very serious interaction between red clover and methotrexate not previously documented. It highlights the potential pitfalls of concomitant use of herbal remedies and conventionally prescribed drugs and the importance of advising our patients about OTC drugs. A 52-year-old woman attended her general practitioner for advice on menopausal flushing. She was on methotrexate weekly injections for severe psoriasis and was not keen to consider anything that would possibly affect her skin. Alternative therapies were discussed and red clover was suggested. This was bought OTC. After the third day of taking red clover capsules (430 mg), the patient developed severe vomiting and epigastric pain. She contacted the dermatology clinic that administers the methotrexate injection and was thought to have symptoms suggestive of methotrexate toxicity even though her liver function tests remained within normal levels. She had been receiving methotrexate injections for nearly two years with no adverse effects. The only new drug that had been started was red clover and this was thought to be the probable cause of the toxicity. It was withdrawn. The patient made a full recovery and received her next injection of methotrexate with no adverse effects. The interaction was reported to the MHRA with a yellow card.
Exploring patient priorities among long-term conditions in multimorbidity: A qualitative secondary analysis
Authors: Cheraghi-Sohi Sudeh , Morden Andrew , Bower Peter , Kennedy Anne , Rogers Anne , Richardson Jane , Sanders Tom , Stevenson Fiona , Ong Bie N
Published: September 2013

Objective:

A lack of agreement between health-care providers and patient priorities can impact the health-care provider–patient relationship, treatment concordance and potentially health outcomes. Evidence suggests that people living with multiple morbidities do prioritise among their long-term conditions. However, the evidence revealing the underlying reasons behind this prioritisation remains limited. Given the potential implications for day-to-day self-management activity and ultimately patient outcomes, this study aims to explore how and why people with multimorbidity prioritise some long-term conditions over others and what the potential implications may be for self-management activity, and in turn, suggest how such information may help clinicians negotiate the management of multimorbidity patients.

Methods:

A secondary analysis of qualitative data was conducted utilising four existing data sets collated from the three research centres involved. Purposive sampling provided a sample of 41 participants who had multimorbidity. The research team collectively coded and analysed the data thematically.

Results:

All participants, except two, identified one ‘main’ priority long-term condition. Current priorities were arrived at by participants making comparisons between their long-term conditions, specifically by trading off the various attributes, impacts and perceived consequences of their individual long-term conditions. Two main themes emerged as to why participants identified a particular main long-term condition: (a) proximate issues surrounding barriers to functional health and (b) prioritisation of long-term conditions perceived to have a particular future risk.

Conclusions:

The recent focus on multimorbidity within the medical literature reflects its prevalence. It is therefore important to understand the complexities of the multimorbidity illness experience. We have added to the limited literature on condition prioritisation by revealing some novel understandings of the process of condition prioritisation which can feed into patient–provider consultations in order to allow better communication and treatment planning as well as, ultimately, optimise patient outcomes.
Tweeting News Articles
Authors: Bastos Marco Toledo , Zago Gabriela
Published: September 2013

In this article we investigate the impact of social media readership to the editorial profile of newspapers. We analyze tweets containing links to news articles from eight of the largest national newspapers in the United States, United Kingdom, Spain, Brazil, and Germany. The data collection follows the first two weeks of October 2012 and includes 2,842,699 tweets with links to news articles. Twitter-shortened links were resolved using a three-pass routine and assigned to 1 of the 21 newspaper sections. We found the concentration of links to news articles posted by top users to be lower than reported in the literature and the strategy of relaying headlines on Twitter via automatic news aggregators (feeds) to be inefficient. The results of this investigation show which sections of a newspaper are the most and least read by readers in different parts of the world, with German readers placing greater emphasis on Politics and Economy; Brazilians on Sports and Arts; Spaniards on Local and National news; Britons and Americans on Opinion and World news. We also found that German and Spanish readers are more likely to read multiple national newspapers, while British readers more often resort to foreign sources of news. The results confirm that feedback to news items from a large user base is pivotal for the replication of content and that newspapers and news items can be clustered according to the editorial profile and principles of newsworthiness inherited from legacy media. The results of this investigation shed light onto the networked architecture of journalism that increasingly depends on readership agency.
High Prevalence of Low Skeletal Muscle Mass Associated with Male Gender in Midlife and Older HIV-Infected Persons Despite CD4 Cell Reconstitution and Viral Suppression
Authors: Wasserman Peter , Segal-Maurer Sorana , Rubin David S.
Published: September 2013

Therapeutic goals for HIV-infected patients receiving antiretroviral therapy include minimizing risk of future physical disability. Presarcopenia and sarcopenia precede age-associated physical disability. We investigated their prevalence and the predictive value of patient mid-upper arm circumference (MUAC) for them. Eighty community-dwelling patients ≥45 years old demonstrating durable viral suppression were evaluated. Sarcopenia was defined as low skeletal muscle index (SMI, skeletal muscle kg/height m2) and either low strength or poor performance by handgrip dynamometry and gait speed, respectively. Presarcopenia was defined as low SMI only. MUAC was interpreted according to National Health Statistics percentile. Prevalence of sarcopenia and presarcopenia was 5.0% and 20.0%, respectively. Male gender (odds ratio [OR] 10.72; P < .026), recreational psychoactive substance use (OR 5.13; P < .037), and intravenous drug use transmission category (OR 6.94; P <.0327) were associated with presarcopenia. Higher body mass index (OR 0.80; P < .0007), MUAC (OR 0.83; P < .024), and large skeletal frame (OR 0.09; P < .003) were negatively associated with presarcopenia. Finding that a participant did not have a MUAC <25th percentile on physical examination had a 90.4% negative predictive value for presarcopenia. Although sarcopenia was uncommon, presarcopenia was highly prevalent in midlife and older HIV-infected males. Determination of MUAC percentile may identify those least likely to demonstrate skeletal muscle deficit and improve patient selection for mass and function testing.
Blood Transfusion–Associated HIV Infection in Children in Ibadan, Nigeria
Authors: Brown Biobele J. , Oladokun Regina E. , Ogunbosi Babatunde O. , Osinusi Kikelomo
Published: September 2013

Introduction:

This study describes the epidemiologic features and clinical course of children with blood transfusion-associated HIV infection (TAHI) in Ibadan, Nigeria.

Methodology:

All children diagnosed to have TAHI at the University College Hospital, Ibadan, were studied and compared with children who acquired HIV vertically using the pediatric HIV database in the hospital.

Results:

Transfusion-associated HIV infection accounted for 14 (2.3%) of the 597 children diagnosed to have HIV infection between January 2004 and December 2011. The mean age at diagnosis of TAHI was 10.2 years and that of vertically acquired HIV infection was 3.9 years ( P < .001). In 9 cases, blood transfusion took place in private hospitals and in 5 cases in public hospitals. Median interval between infection and diagnosis of AIDS was 84 months in cases with TAHI and 48 months in vertically acquired cases ( P = .542).

Conclusion:

Optimal blood safety practices are advocated for prevention of TAHI in Nigeria.
CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism
Authors: Zucchetto Antonella , Caldana Chiara , Benedetti Dania , Tissino Erika , Rossi Francesca Maria , Hutterer Evelyn , Pozzo Federico , Bomben Riccardo , Dal Bo Michele , D’Arena Giovanni , Zaja Francesco , Pozzato Gabriele , Di Raimondo Francesco , Hartmann Tanja N. , Rossi Davide , Gaidano Gianluca , Del Poeta Giovanni , Gattei Valter
Published: September 2013

Key Points

CD49d, a negative prognosticator with a key role for microenvironmental interactions in CLL, is near universally expressed in trisomy 12 CLL. CD49d overexpression in trisomy 12 CLL is regulated by a methylation-dependent mechanism.
Inhibition of actin polymerization decreases osteogeneic differentiation of mesenchymal stem cells through p38 MAPK pathway
Authors: Sonowal Himangshu , Kumar Atul , Bhattacharyya Jina , Gogoi Pabitra Kumar , Jaganathan Bithiah Grace
Published: September 2013

Background

Mesenchymal Stem Cells (MSC) are important candidates for therapeutic applications due to their ex vivo proliferation and differentiation capacity. MSC differentiation is controlled by both intrinsic and extrinsic factors and actin cytoskeleton plays a major role in the event. In the current study, we tried to understand the initial molecular mechanisms and pathways that regulate the differentiation of MSC into osteocytes or adipocytes.

Results

We observed that actin modification was important during differentiation and differentially regulated during adipogenesis and osteogenesis. Initial disruption of actin polymerization reduced further differentiation of MSC into osteocytes and osteogenic differentiation was accompanied by increase in ERK1/2 and p38 MAPK phosphorylation. However, only p38 MAPK phosphorylation was down regulated upon inhibition of actin polymerization which as accompanied by decreased CD49E expression.

Conclusion

Taken together, our results show that actin modification is a pre-requisite for MSC differentiation into osteocytes and adipocytes and osteogenic differentiation is regulated through p38 MAPK phosphorylation. Thus by modifying their cytoskeleton the differentiation potential of MSC could be controlled which might have important implications for tissue repair and regeneration.
FGF2-induced effects on transcriptome associated with regeneration competence in adult human fibroblasts
Authors: Kashpur Olga , LaPointe David , Ambady Sakthikumar , Ryder Elizabeth F , Dominko Tanja
Published: September 2013

Background

Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration responsein vivoover scar formation. Here, we compare the transcriptomes of control adult human dermal fibroblasts and induced regeneration-competent (iRC) fibroblasts to identify transcriptional changes that may be related to their regeneration competence.

Results

We identified a unique gene-expression profile that characterizes FGF2-induced iRC fibroblast phenotype. Significantly differentially expressed genes due to FGF2 treatment were identified and analyzed to determine overrepresented Gene Ontology terms. Genes belonging to extracellular matrix components, adhesion molecules, matrix remodelling, cytoskeleton, and cytokines were determined to be affected by FGF2 treatment.

Conclusions

Transcriptome analysis comparing control adult human fibroblasts with FGF2-treated fibroblasts identified functional groups of genes that reflect transcriptional changes potentially contributing to their regeneration competence. This comparative transcriptome analysis should contribute new insights into genes that characterize cells with greater regenerative potential.
Assessment of weight-related factors of adolescents by private practitioners
Authors: Huang Rong , Ho Sai Yin , Lo Wing Sze , Lam Tai Hing
Published: September 2013

Background

Few studies have examined how common physicians assess various weight-related variables and patient characteristics that predict such assessments based on adolescents’ reports. We aimed to examine how common adolescents received weight-related physical measurements and lifestyle enquiries (dietary habits and physical activity) from private practitioners and to identify factors associated with these assessments.

Methods

In the Hong Kong Student Obesity Surveillance (HKSOS) project, 33692 students (44.9% boys; mean age 14.8, SD 1.9 years, age range 11–18) from 42 randomly selected schools completed an anonymous questionnaire. The students were asked “In the past 12 months, has any private practitioners (or their nurses) measured or asked about these items?” Response options included height, weight, waist circumference (WC), blood pressure (BP), BMI, diet, and physical activity. Weight status was based on self-reported weight and height. Logistic regression was used to identify student characteristics associated with each assessment. Analyses were conducted using STATA 10.0.

Results

Among 13283 students who had doctor consultations in the past 12 months, 37.9% received physical measurements or lifestyle enquiries, with weight (20.8%), height (16.8%) and blood pressure (11.5%) being the most common, followed by diet (8.1%), BMI (6.3%), WC and physical activity (both 4.6%). In general, adolescents who were female, older, underweight or overweight/obese, had parents with higher education level, and had actively asked private practitioners for advice about weight were more likely to receive assessments of weight-related factors.

Conclusions

Weight-related factors in adolescents were infrequently assessed by private practitioners in Hong Kong. Generally, unhealthy weight, higher parental education and advice-seeking by adolescents predicted these assessments.
Incidence and prevalence of multiple sclerosis in Europe: a systematic review
Authors: Kingwell Elaine , Marriott James J , Jetté Nathalie , Pringsheim Tamara , Makhani Naila , Morrow Sarah A , Fisk John D , Evans Charity , Béland Sarah Gabrielle , Kulaga Sophie , Dykeman Jonathan , Wolfson Christina , Koch Marcus W , Marrie Ruth Ann
Published: September 2013

Background

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality.

Methods

A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study.

Results

There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates.

Conclusions

Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.
Comparison of clinical and dental panoramic findings: a practice-based crossover study
Authors: Moll Marc A , Seuthe Miriam , von See Constantin , Zapf Antonia , Hornecker Else , Mausberg Rainer F , Ziebolz Dirk
Published: September 2013

Background

Aim was to compare clinical findings with x-ray findings using dental panoramic radiography (DPR). In addition, type and frequency of secondary findings in x-rays were investigated.

Methods

Patients were selected on the basis of available DPRs (not older than 12 months). No therapeutic measures were permitted between the DPR and the clinical findings. The clinical findings were carried out by several investigators who had no knowledge of the purpose of the study. A calibrated investigator established the x-ray findings, independently and without prior knowledge of the clinical findings. The evaluation parameters for each tooth were: missing, healthy, carious, restorative or prosthetically sufficient or insufficient treatment. Type and frequency of additional findings in the DPR were documented, e.g. quality of a root canal filling and apical changes.

Results

Findings of 275 patients were available. Comparison showed a correspondence between clinical and radiographic finding in 93.6% of all teeth (n = 7,789). The differences were not significant (p > 0.05). Regarding carious as well as insufficiently restored or prosthetically treated teeth, respectively there were significant differences between the two methods (p < 0.05). The DPRs showed additional findings: root fillings in 259 teeth and 145 teeth with periapical changes.

Conclusions

With reference to the assessment of teeth, there was no difference between the two methods. However, in the evaluation of carious as well as teeth with insufficiently restorative or prosthetic treatment, there was a clear discrepancy between the two methods. Therefore, it would have been possible to have dispensed with x-rays. Nevertheless, additional x-ray findings were found.
Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression
Authors: Li Xiao-Lei , Jia Lan-Ling , Shi Mu-Mu , Li Xin , Li Zhong-Hua , Li Hui-Feng , Wang En-Hua , Jia Xin-Shan
Published: September 2013

Background

Oct4 is a major transcription factor related to stem cell self-renewal and differentiation. To fulfill its functions, it must be able to enter the nucleus and remain there to affect transcription. KPNA2, a member of the karyopherin family, plays a central role in nucleocytoplasmic transport. The objective of the current study was to examine the association between Oct4 and KPNA2 expression levels with regard to both the clinicopathological characteristics and prognoses of patients with non-small-cell lung cancer (NSCLC).

Methods

Immunohistochemistry was used to detect the expression profile of Oct4 and KPNA2 in NSCLC tissues and adjacent noncancerous lung tissues. Real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression profiles of Oct4 and KPNA2 in lung cancer cell lines. Small interfering RNAs were used to deplete Oct4 and KPNA2 expressions. Double immunofluorescence was used to detect Oct4 expression in KPNA2 knockdown cells. Co-immunoprecipitation was used to detect the interaction of Oct4 and KPNA2.

Results

Oct4 was overexpressed in 29 of 102 (28.4%) human lung cancer samples and correlated with differentiation (P = 0.002) and TNM stage (P = 0.003). KPNA2 was overexpressed in 56 of 102 (54.9%) human lung cancer samples and correlated with histology (P = 0.001) and differentiation (P = 0.045). Importantly, Oct4 and KPNA2 expression levels correlated significantly (P < 0.01). Expression of Oct4 and KPNA2 was associated with short overall survival. In addition, depleting Oct4 and KPNA2 expression using small interfering RNAs inhibited proliferation in lung cancer cell lines. Real-time polymerase chain reaction and western blotting analysis indicated that reduction of KPNA2 expression significantly reduced mRNA and nucleoprotein levels of Oct4. Double immunofluorescence analysis revealed that nuclear Oct4 signals were reduced significantly in KPNA2 knockdown cells. Co-immunoprecipitation experiments revealed that KPNA2 interacts with Oct4 in lung cancer cell lines.

Conclusion

Oct4 and KPNA2 play an important role in NSCLC progression. Oct4 nuclear localization may be mediated by its interaction with KPNA2.
Aptamer-modified magnetic nanoprobe for molecular MR imaging of VEGFR2 on angiogenic vasculature
Authors: Kim Bongjune , Yang Jaemoon , Hwang Myeonghwan , Choi Jihye , Kim Hyun-Ouk , Jang Eunji , Lee Jung Hwan , Ryu Sung-Ho , Suh Jin-Suck , Huh Yong-Min , Haam Seungjoo
Published: September 2013

Nucleic acid-based aptamers have been developed for the specific delivery of diagnostic nanoprobes. Here, we introduce a new class of smart imaging nanoprobe, which is based on hybridization of a magnetic nanocrystal with a specific aptamer for specific detection of the angiogenic vasculature of glioblastoma via magnetic resonance (MR) imaging. The magnetic nanocrystal imaging core was synthesized using the thermal decomposition method and enveloped by carboxyl polysorbate 80 for water solubilization and conjugation of the targeting moiety. Subsequently, the surface of the carboxylated magnetic nanocrystal was modified with amine-functionalized aptamers that specifically bind to the vascular growth factor receptor 2 (VEGFR2) that is overexpressed on angiogenic vessels. To assess the targeted imaging potential of the aptamer-conjugated magnetic nanocrystal for VEGFR2 markers, the magnetic properties and MR imaging sensitivity were investigated using the orthotopic glioblastoma mouse model. In in vivo tests, the aptamer-conjugated magnetic nanocrystal effectively targeted VEGFR2 and demonstrated excellent MR imaging sensitivity with no cytotoxicity.
Geographical variation and factors influencing modern contraceptive use among married women in Ethiopia: evidence from a national population based survey
Authors: Lakew Yihunie , Reda Ayalu A , Tamene Habtamu , Benedict Susan , Deribe Kebede
Published: September 2013

Background

Modern contraceptive use persists to be low in most African countries where fertility, population growth, and unmet need for family planning are high. Though there is an evidence of increased overall contraceptive prevalence, a substantial effort remains behind in Ethiopia. This study aimed to identify factors associated with modern contraceptive use and to examine its geographical variations among 15–49 married women in Ethiopia.

Methods

We conducted secondary analysis of 10,204 reproductive age women included in the 2011 Ethiopia Demographic and Health Survey (DHS). The survey sample was designed to provide national, urban/rural, and regional representative estimates for key health and demographic indicators. The sample was selected using a two-stage stratified sampling process. Bivariate and multivariate logistic regressions were applied to determine the prevalence of modern contraceptive use and associated factors in Ethiopia.

Results

Being wealthy, more educated, being employed, higher number of living children, being in a monogamous relationship, attending community conversation, being visited by health worker at home strongly predicted use of modern contraception. While living in rural areas, older age, being in polygamous relationship, and witnessing one’s own child’s death were found negatively influence modern contraceptive use. The spatial analysis of contraceptive use revealed that the central and southwestern parts of the country had higher prevalence of modern contraceptive use than that of the eastern and western parts.

Conclusion

The findings indicate significant socio-economic, urban–rural and regional variation in modern contraceptive use among reproductive age women in Ethiopia. Strengthening community conversation programs and female education should be given top priority.
Influence of gender roles and rising food prices on poor, pregnant women’s eating and food provisioning practices in Dhaka, Bangladesh
Authors: Levay Adrienne V , Mumtaz Zubia , Faiz Rashid Sabina , Willows Noreen
Published: September 2013

Background

Maternal malnutrition in Bangladesh is a persistent health issue and is the product of a number of complex factors, including adherence to food 'taboos’ and a patriarchal gender order that limits women’s mobility and decision-making. The recent global food price crisis is also negatively impacting poor pregnant women’s access to food. It is believed that those who are most acutely affected by rising food prices are the urban poor. While there is an abundance of useful quantitative research centered on maternal nutrition and food insecurity measurements in Bangladesh, missing is an understanding of how food insecurity is experienced by people who are most vulnerable, the urban ultra-poor. In particular, little is known of the lived experience of food insecurity among pregnant women in this context. This research investigated these lived experiences by exploring food provisioning strategies of urban, ultra-poor, pregnant women. This knowledge is important as discussions surrounding the creation of new development goals are currently underway.

Methods

Using a focused-ethnographic approach, household food provisioning experiences were explored. Data from participant observation, a focus group discussion and semi-structured interviews were collected in an urban slum in Dhaka, Bangladesh. Interviews were undertaken with 28 participants including 12 pregnant women and new mothers, two husbands, nine non-pregnant women, and five health care workers.

Results

The key findings are: 1) women were aware of the importance of good nutrition and demonstrated accurate, biomedically-based knowledge of healthy eating practices during pregnancy; 2) the normative gender rules that have traditionally constrained women’s access to nutritional resources are relaxing in the urban setting; however 3) women are challenged in accessing adequate quality and quantities of food due to the increase in food prices at the market.

Conclusions

Rising food prices and resultant food insecurity due to insufficient incomes are negating the recent efforts that have increased women’s knowledge of healthy eating during pregnancy and their gendered empowerment. In order to maintain the gains in nutritional knowledge and women’s increased mobility and decision-making capacity; policy must also consider the global political economy of food in the creation of the new development goals.
Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes
Authors: Wang Fei , Guo Ye , Chen Qian , Yang Zhuo , Ning Ning , Zhang Yujuan , Xu Yonggang , Xu Xiaodong , Tong Chunrong , Chai Li , Cui Wei
Published: September 2013

Background

Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course. Predicting disease progression is difficult due to lack of specific molecular marker(s). SALL4 plays important roles in normal hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to acute myeloid leukemia (AML) transformation. However, the role of SALL4 in human MDS has not been extensively investigated. In this study, we evaluate the diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in a cohort of MDS patients.

Methods

Fifty-five newly diagnosed MDS, twenty MDS-AML, and sixteen post-treatment MDS patients were selected for our study along with ten healthy donors.

Results

We demonstrated that SALL4 was over-expressed in MDS patients and proportionally increased in MDS patients with high grade/IPSS scores. This expression pattern was similar to that of Bmi-1, an important marker in predicting MDS/AML progression. In addition, the level of SALL4 was positively correlated with increased blast counts, high-risk keryotypes and increased significantly in MDS-AML transformation. Furthermore, higher level of SALL4 expression was associated with worse survival rates and SALL4 level decreased following effective therapy.

Conclusions

To the best of our knowledge, this is the largest series and the first to report the expression pattern of SALL4 in detail in various subtypes of MDS in comparison to that of Bmi-1. We conclude that SALL4 is a potential molecular marker in predicting the prognosis of MDS.
Anesthetic management of a patient with a giant ovarian tumor containing 83 l of fluid
Authors: Bamba Keiko , Watanabe Tatsunori , Kohno Tatsuro
Published: September 2013

We report the anesthetic management of a patient scheduled for tumor resection with a giant ovarian tumor containing 83 l of fluid. A 59-year-old woman [height 154 cm; weight 146 kg (ideal: 52 kg)] with a giant ovarian tumor was scheduled for tumor resection. Her preoperative abdominal circumference was 194 cm, which made supine positioning difficult. The thoracoabdominal computed tomography revealed a right giant cystic ovarian tumor with an estimated mass of 100 kg. Evidence of malignant tumor was not observed. In the operation room, she was intubated using a video laryngoscope (Airway Scope®, Hoya, Tokyo, Japan) in a semirecumbent position under conscious sedation. Following general anesthesia, the tumor fluid was gradually aspirated at a rate of 500 ml/min, and during this procedure, spontaneous respiration was preserved with pressure support ventilation. After the fluid was drained, the tumor was resected in a supine position. There were no major perioperative complications in hemodynamic and respiratory status, such as supine hypotensive syndrome or re-expansion pulmonary edema. Her weight decreased to 50 kg postoperatively. Maintenance of spontaneous respiration and slow aspiration of the tumor fluid prevented respiratory and hemodynamic failure and resulted in safe anesthesia management during giant ovarian tumor resection.
Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy
Authors: Baraf Herbert SB , Becker Michael A , Gutierrez-Urena Sergio R , Treadwell Edward L , Vazquez-Mellado Janitzia , Rehrig Claudia D , Ottery Faith D , Sundy John S , Yood Robert A
Published: September 2013

Introduction

Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.

Methods

Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.

Results

Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).

Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).

Conclusions

Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.

Trial registrations

NCT00325195, NCT01356498
Assessing tumor contrast in radiographically dense breast tissue using Diffuse Optical Spectroscopic Imaging (DOSI)
Authors: Leproux Anaïs , Durkin Amanda , Compton Montana , Cerussi Albert E , Gratton Enrico , Tromberg Bruce J
Published: September 2013

Introduction

Radiographic density adversely affects the performance of X-ray mammography and can be particularly problematic in younger and high-risk women. Because of this limitation, there is significant ongoing effort to develop alternative cancer screening and detection strategies for this population. This pilot study evaluates the potential of Diffuse Optical Spectroscopic Imaging (DOSI) to image known tumors in dense breast tissue.

Methods

We performed a retrospective analysis on 24 radiographically dense breast cancer subjects measured with DOSI over a four-year period (Breast Imaging Reporting and Data System - BI-RADS, category 3 and 4, average age = 39 ± 7.6, average maximum size 31 ± 17 mm). Two previously-described DOSI contrast functions, the tissue optical index (TOI) and the specific tumor component (STC), which are based upon the concentrations and spectral signatures of hemoglobin, water and lipids, respectively, were used to form 2D optical images of breast tumors.

Results

Using TOI and STC, 21 out of 24 breast tumors were found to be statistically different from the surrounding highly vascularized dense tissue and to be distinguishable from the areolar region. For these patients, the tumor to normal contrast was 2.6 ± 1.2 (range 1.3 to 5.5) and 10.0 ± 7.5 (range 3.3 to 26.4) for TOI and STC, respectively. STC images were particularly useful in eliminating metabolic background from the retroareolar region which led to identification of two out of four retroareolar tumors.

Conclusions

Using both the abundance and the disposition of the tissue chromophores recovered from the DOSI measurements, we were able to observe tumor contrast relative to dense breast tissue. These preliminary results suggest that DOSI spectral characterization strategies may provide new information content that could help imaging breast tumors in radiographically dense tissue and in particular in the areolar complex.
PintlincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
Authors: Marín-Béjar Oskar , Marchese Francesco P , Athie Alejandro , Sánchez Yolanda , González Jovanna , Segura Victor , Huang Lulu , Moreno Isabel , Navarro Alfons , Monzó Mariano , García-Foncillas Jesús , Rinn John L , Guo Shuling , Huarte Maite
Published: September 2013

Background

The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway.

Results

Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor.

Conclusions

Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.
STAT5 polarization promotes iTregs and suppresses human T-cell alloresponses while preserving CTL capacity
Authors: Betts Brian C , Veerapathran Anandharaman , Pidala Joseph , Yu Xue-Zhong , Anasetti Claudio
Published: September 2013

Alloreactivity negatively influences outcomes of organ transplantation or HCT from allogeneic donors. Standard pharmacologic immune suppression impairs T-cell function and jeopardizes the beneficial reconstitution of Tregs. Murine transplantation models have shown that STAT3 is highly expressed in alloreactive T cells and may be therapeutically targeted. The influence and effects of STAT3 neutralization in human alloreactivity, however, remain to be elucidated. In this study, S3I-201, a selective small-molecule inhibitor of STAT3, suppressed human DC-allosensitized T-cell proliferation and abrogated Th17 responses. STAT3 blockade significantly enhanced the expansion of potent iTregs and permitted CD8+ cytolytic effector function. Mechanistically, S3I-201 polarized the ratio of STAT phosphorylation in favor of STAT5 over STAT3 and also achieved a significant degree of Foxp3 demethylation among the iTregs. Conversely, selective impairment of STAT5 phosphorylation with CAS 285986-31-4 markedly reduced iTregs. STAT3 represents a relevant target for achieving control over human alloresponses, where its suppression facilitates STAT5-mediated iTreg growth and function.