bluuebunny/crossref_metadata_2025 huggingface dataset:
Docosahexaenoic Acid and Periodontitis in Adults
Authors: Naqvi A.Z. , Hasturk H. , Mu L. , Phillips R.S. , Davis R.B. , Halem S. , Campos H. , Goodson J.M. , Van Dyke T.E. , Mukamal K.J.
Published: June 2014

Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1β (IL-6 and IL-1β). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (–0.29 ± 0.13; p = .03) and gingival index (–0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (–5.3 ng/mL, standard error [SE] = 2.4, p = .03) and IL-1β (–20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (–1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved periodontal outcomes in people with periodontitis, indicating its potential therapeutic efficacy (clinicaltrials.gov NTC01976806).
The Effects of a Tier 3 Intervention on the Mathematics Performance of Second Grade Students With Severe Mathematics Difficulties
Authors: Bryant Brian R. , Bryant Diane Pedrotty , Porterfield Jennifer , Dennis Minyi Shih , Falcomata Terry , Valentine Courtney , Brewer Chelsea , Bell Kathy
Published: June 2014

The purpose of this study was to determine the effectiveness of a systematic, explicit, intensive Tier 3 (tertiary) intervention on the mathematics performance of students in second grade with severe mathematics difficulties. A multiple-baseline design across groups of participants showed improved mathematics performance on number and operations concepts and procedures, which are the foundation for later mathematics success. In the previous year, 12 participants had experienced two doses (first and second semesters) of a Tier 2 intervention. In second grade, the participants continued to demonstrate low performance, falling below the 10th percentile on a researcher-designed universal screener and below the 16th percentile on a distal measure, thus qualifying for the intensive intervention. A project interventionist, who met with the students 5 days a week for 10 weeks (9 weeks for one group), conducted the intensive intervention. The intervention employed more intensive instructional design features than the previous Tier 2 secondary instruction, and also included weekly games to reinforce concepts and skills from the lessons. Spring results showed significantly improved mathematics performance (scoring at or above the 25th percentile) for most of the students, thus making them eligible to exit the Tier 3 intervention.
Relative Clauses in Southeast Asian Englishes
Authors: Suárez-Gómez Cristina
Published: June 2014

This article examines adnominal relative clauses in Asian Englishes, looking specifically at the distribution of relative words. Drawing on data from the ICE corpora, it compares the varieties spoken in India, Hong Kong, and Singapore. In particular it considers (a) linguistic factors such as the degree of animacy of the antecedent and the syntactic function realized by the relative word in the relative clause and (b) extralinguistic issues such as the effect of cognitive constraints typically associated with language contact situations and the impact of sociocultural factors, which can often determine differences between varieties. An examination of these issues uncovers specificities in the distribution of relative words that are related both to the different degrees of development of the corresponding local standard variety and to the interaction between the superstrate and the different substrate languages.
CEO Optimism and Analyst Forecast Bias
Authors: Wong M. H. Franco , Zhang X. Frank
Published: June 2014

We examine analysts’ forecast behavior in a setting in which CEOs are optimistic and analysts react rationally to CEO optimism. We document that the bias in analysts’ consensus forecasts is negatively related to the level of CEO optimism. The negative relation is stronger for small firms, firms with low analyst followings, and firms with high uncertainty. Analysts revise downward their forecasts for next year’s earnings less relative to their revision for current year’s earnings for firms with more optimistic CEOs, a result consistent with optimistic CEOs are subject to self-attribution bias. The stock price reactions to downward forecast revisions and missing analysts’ forecasts are less negative for firms with optimistic CEOs, indicating that investors understand the implications of CEO optimism for analysts’ forecast bias and subsequent revisions.
Factors Influencing Escherichia coli and Enterococcus durans Growth in Parenteral Nutrition With and Without Lipid Emulsion to Inform Maximum Duration of Infusion Policy Decisions
Authors: Austin Peter David , Hand Kieran Sean , Elia Marinos
Published: June 2014

Background: Recommendations effectively restrict the infusion duration of lipid‐containing parenteral nutrition (PN) from a single bag, purportedly because it encourages growth of potential microbial contaminants more than lipid‐free PN. Since other variables, including osmolarity, may independently affect microbial growth, this study examined variables affecting growth of Escherichia coli and Enterococcus durans in PN infusates. Materials and Methods: Growth of E coli and E durans was assessed in quadruplicate in 12 different PN infusates, with and without lipid, in varying glucose concentrations. Results: Results are presented as mean log10 colony‐forming units (cfu)/mL ± SEM at 48 hours. The log10cfu/mL of both E coli and E durans in PN increased considerably after adjustment for baseline log10cfu/mL and pH, from 1.093 to 2.241 (P < .001) and from 0.843 to 3.451 (P < .001) respectively. Growth of each microorganism was independently increased by lipid inclusion, or increasing the proportion of nonnitrogen energy from lipid, and reduced by raising the glucose concentration or energy density. Increasing the osmolarity of lipid‐PN with glucose or sodium chloride reduced growth but only significantly for sodium chloride (E coli, P = .025; E durans, P = .045). Induced changes in pH affected the growth of the 2 organisms differently. Conclusion: The presence of lipid and an increasing proportion of energy from lipid in PN favored the growth of E coli and E durans. Osmolarity changes and the nutrient type causing these changes independently affect the growth of these microbes. Each effect needs to be considered when establishing guidelines based on the growth of potential contaminants in different types of PN.
Intermittent warm blood versus cold crystalloid cardioplegia for myocardial protection: a propensity score-matched analysis of 12-year single-center experience
Authors: de Jonge M , van Boxtel AG , Soliman Hamad MA , Mokhles MM , Bramer S , Osnabrugge RLJ , van Straten AHM , Berreklouw E
Published: June 2014

Objectives:

This study analyzes the efficacy in myocardial protection of two types of cardioplegia solutions, namely, blood and crystalloid cardioplegia, both given intermittently in patients undergoing coronary artery bypass grafting (CABG).

Methods:

Adult patients undergoing primary isolated coronary artery bypass grafting between January 1998 and January 2011 with cardiopulmonary bypass, using either blood or crystalloid cardioplegia, were identified in our database. Propensity score matching was performed to create comparable patient groups. Multivariate logistic regression analysis was performed to identify independent risk factors for perioperative myocardial damage. The primary endpoint of the study was the maximum creatine kinase-MB (CK-MB) value within 5 days postoperatively with a cut-off point of 100 U/L. Early mortality and perioperative low cardiac output syndrome in both groups were compared.

Results:

The study included 7138 CABG patients: 3369 patients using crystalloid cardioplegia and 3769 using blood cardioplegia. After propensity score matching, 2585 patients per study group remained for the analysis. Wilcoxon signed-rank test revealed significantly higher CK-MB levels in patients operated with the use of blood cardioplegia. Multivariate regression analysis identified blood cardioplegia as an independent risk factor for elevated CK-MB levels. However, it was associated with lower aspartate aminotransferase (AST) levels. The type of cardioplegia had no influence on early mortality, postoperative low cardiac output syndrome or intensive care unit stay.

Conclusions:

Blood cardioplegia was identified as an independent risk factor for elevated levels of CK-MB after CABG, but was associated with lower AST levels. The authors conclude that the type of cardioplegia had no significant influence on clinical outcome.
Relations Between Student Perceptions of Their School Environment and Academic Achievement
Authors: Gietz Carmen , McIntosh Kent
Published: June 2014

This study examined student perceptions of their school environment (specifically, safety and inclusion in the school, experiences being bullied, and clear expectations for behaviour) and their relation with academic achievement at the school level. Participants were students in 969 elementary schools and 73 middle schools who took part in a provincewide achievement test and student satisfaction survey in Canada. Hierarchical multiple regression analyses were conducted to determine the amount of variance in student achievement explained by student perceptions of the school environment when controlling for school-level poverty and accounting for nesting by district. Results showed that perceptions of the school environment were significantly associated with academic success, above and beyond effects of school-level poverty and district. These results are discussed with regard to critical targets for enhancing the school environment to maximize academic achievement.
Hurricane Sandy
Authors: Trento Laura , Allen Sarah
Published: June 2014

Natural disasters and weather‐related emergencies can strike at a moment's notice. Individuals with chronic health conditions and other special needs are especially vulnerable. Basic services such as water, electricity, gas, and telephone service may not be available. Home parenteral and enteral nutrition consumers are at a serious risk as they depend on clean water and power for nutrient delivery. Creating a comprehensive emergency preparedness plan is imperative for both the home parenteral and enteral consumer and home care provider to ensure that special needs are met. Home care providers can assist home parenteral and enteral consumers in disaster and emergency planning.
Violence and the Code of the Street
Authors: Naterer Andrej
Published: June 2014

This article explores violence among street children in Makeevka, Ukraine. Drawing on qualitative and quantitative data gathered during longitudinal field research, extra-, intra-, and inter-group violence is analyzed with an emphasis on the child’s situational interpretation and adoption of the code of the street through subsequent code/identity switching and subcultural reactions. The main findings suggest that street children subculture has developed a unique code based on the need to survive and on solidarity and reciprocity; violent acts emerging among them must be understood within this context. The influence of violence on the children’s lives and street careers is considered, and alternative explanations of violence are discussed.
New Literacy Studies
Authors: Naraian Srikala , Surabian Mark
Published: June 2014

Even as research continues to suggest the potential of assistive technology for improving student outcomes, it remains under-utilized in schools. Among numerous challenges to the effective utilization of assistive technology, research has suggested that educators are inadequately prepared to consider and implement the use of such technologies. In this article, we complement the effort to delineate the competencies needed by teachers for this purpose by suggesting that New Literacy Studies can serve as a generative frame to stimulate the dispositions necessary for a strong commitment to the use of assistive technology (AT) and to increase accessibility in the classroom. Specifically, we examine constructs within sociocultural approaches to literacy, multimodality, and critical literacy, thereby strengthening the interconnections between curriculum, pedagogy, and technology-based support for students with disabilities. We offer several implications of this approach for educators and teacher educators.
The effect of the temperature on the wear and resistance of automotive connectors subjected to vibration tests
Authors: El Abdi Rochdi , Benjemâa Noureddine
Published: June 2014

A connector is designed to allow the passage of a current across different electrical systems. A connector subjected to car vibrations and a high temperature can suffer damage. This damage leads to a rapid degradation in the electrical performance, which results in a considerable increase in the electrical contact resistance. This work aims to address the influences of a variety of factors such as the fretting amplitude, the frequency, the temperature and the current on the performance of tin-plated automotive connectors. The changes due to the degradation in the electric conduction of the connectors under mechanical vibrations and temperature cycles are analysed. A detailed analysis of the contact surface is made using a profilometer, an optical microscope and a scanning electron microscope.
Slum types and adaptation strategies: identifying policy-relevant differences in Bangalore
Authors: Krishna Anirudh , Sriram M S , Prakash Purnima
Published: June 2014

An empirical analysis of the lived experiences of more than 2,000 households in different Bangalore slums shows how migration patterns, living conditions, livelihood strategies and prospects for the future vary widely across distinct types of slums that were initially identified from satellite images and studied over a 10-year period. Shocks and responses vary in nature and intensity, and coping and accumulative strategies diverge across slum types. More fine-grained policy analyses that recognize this diversity of slum types will help people deal with shocks and increase resilience more effectively.
Genital ulcers: it is not always simplex …
Authors: Haidari G , MacMahon E , Tong CYW , White JA
Published: June 2014

Patients with vulval aphthae, also termed Lipschütz ulcers, often present to genitourinary medicine clinics. Typically, these ulcers present as acute, painful, vulval ulcers in young women and adolescents. The aetiology is unknown, and often these ulcers are accompanied by flu-like symptoms. Previous case reports have linked such lesions to acute viral infections such as Epstein–Barr virus, cytomegalovirus and influenza A. We report the first case of influenza B virus and adenovirus infections associated with this presentation.
Cerebral large vessel vasculitis in systemic lupus erythematosus
Authors: Böckle B C , Jara D , Aichhorn K , Junker D , Berger T , Ratzinger G , Sepp N T
Published: June 2014

Neuropsychiatric systemic lupus erythematosus (NPSLE) is defined by involvement of the central nervous system in systemic lupus erythematosus (SLE), with a wide range of both neurological and psychiatric manifestations. Although its aetiopathogenesis is not fully elucidated, NPSLE seems to be a consequence of cerebral vascular pathology including thromboembolism, small-vessel vasculopathy and, in rare cases, true vasculitis. Cerebral vasculitis is rare, and cerebral large-vessel vasculitis in SLE is even more unusual. We report the case of a female patient with the diagnosis of SLE. She presented with stroke-like symptoms, headache and vertigo, and palpable purpura on her legs. Further investigations revealed that she suffered from both vasculitis of the cerebral large vessels and coexisting cutaneous small-vessel vasculitis.
Do Caste and Class Define Inequality? Revisiting Education in a Kerala Village
Authors: Scaria Suma
Published: June 2014

Is there a strong correlation between caste and class in access to education, especially higher education? This is the broader question addressed by the study in the context of Kerala, the southernmost state in India, with impressive conventional indicators in education. Micro-level insights based on the study of a village in Kerala show that old forms of inequalities have been replaced by new forms of inequalities in education. Notwithstanding Kerala’s impressive indicators, huge inequalities exist in the educational attainments of the population. The Scheduled Castes (SCs) are still at the bottom of the rankings in enrolment in higher education despite the adoption of a positive discrimination policy and educational subsidy by the state. This situation is explained through an examination of three issues: the perception of the lower employment potential of conventional or mainstream higher education; the educational polices of the state and disparate access to economic resources. The study concludes by offering a few policy recommendations to make higher education more inclusive for marginalised sections of society.
Sight-Singing Pedagogy
Authors: Floyd Eva G. , Haning Marshall A.
Published: June 2014

The purpose of this study was to examine the sight-singing pedagogy content of choral methods textbooks, with the intent of determining what elements of sight-singing pedagogy are most commonly included in these resources. A content analysis was conducted to analyze information related to sight-singing pedagogy in 10 textbooks that are commonly used in undergraduate choral methods courses. Results of this content analysis indicated that although most choral methods textbooks contain some information about teaching sight-singing and music literacy skills, this information is often quite limited and does not include reference to helping students internally organize sound. In addition, information about concepts such as assessment and curriculum planning for sight-singing skills is included in only a small percentage of popular textbooks. Evaluation of these findings can help to illuminate the ways in which textbooks communicate the priorities and core values of a particular field of study, such as choral music education.
Telehealth in the School Setting
Authors: Reynolds Cori A. , Maughan Erin D.
Published: June 2014

Telehealth, the provision of health care through long-distance telecommunications technology, is a tool that can be used by school nurses to address and improve the health status of schoolchildren. The purpose of this literature review is to examine research related to implementation of telehealth in the school setting. A review of the literature was conducted using CINAHL, ERIC, Medline, and PubMed databases and the search terms such as telehealth, telecare, telemedicine, school, and schools. Fifteen research studies related to telehealth in the school setting were identified. Themes identified included benefits, barriers, feasibility, and limitations of telehealth. Implications for practice are presented, along with the potential of telehealth to integrate with the Affordable Care Act. School nurses who use telehealth can further meet the health needs of children in their care. The future of health care and school nursing is changing, and telehealth is a tool that can improve care in an innovative and efficient way.
Internet-Based Cognitive Behavioral Therapy for Adults With ADHD in Outpatient Psychiatric Care
Authors: Pettersson Richard , Söderström Staffan , Edlund-Söderström Kerstin , Nilsson Kent W.
Published: June 2014

Objective: The purpose of the study was to evaluate an Internet-based cognitive behavioral therapy (iCBT) program targeting difficulties and impairments associated with adult ADHD. Method: Forty-five adults diagnosed with ADHD were randomized to either self-help (iCBT self-help format [iCBT-S]), self-help with weekly group sessions (iCBT group-therapy format [iCBT-G]), or a waiting-list control group. Treatment efficacy was measured at pre- and posttreatment and at 6-month follow-up. Results: Intention-to-treat (ITT) analysis showed a significant reduction in ADHD symptoms for the iCBT-S group in comparison with the waiting-list controls at posttreatment, with a between-group effect size of d = 1.07. The result was maintained at 6-month follow-up. No significant difference was found at posttreatment or 6-month follow-up between the iCBT-S and iCBT-G groups. Conclusion: The findings show that a CBT treatment program administered through the Internet can be a promising treatment for adult ADHD. Limitations of the study design and directions for future research are discussed.
Reconsidering the Link Between Impulsivity and Suicidal Behavior
Authors: Anestis Michael D. , Soberay Kelly A. , Gutierrez Peter M. , Hernández Theresa D. , Joiner Thomas E.
Published: June 2014

It is widely accepted that suicidal behavior often occurs with little planning. We propose, however, that suicidal behavior is rarely if ever impulsive—that it is too frightening and physically distressing to engage in without forethought—and that suicidal behavior in impulsive individuals is accounted for by painful and fearsome behaviors capable of enhancing their capacity for suicide. We conducted a meta-analysis of the association between trait impulsivity and suicidal behavior and a critical review of research considering the impulsiveness of specific suicide attempts. Meta-analytic results suggest the relationship between trait impulsivity and suicidal behavior is small. Furthermore, studies examining a mediating role of painful and provocative behaviors have uniformly supported our model. Results from our review suggest that researchers have been unable to adequately measure impulsivity of attempts and that measures sensitive to episodic planning must be developed to further our understanding of this phenomenon.
Reflections on using physical objects as data generation strategies: An example from a study of youth violence and healing
Authors: Berihun Gebrehiwot , Kumsa Martha Kuwee , Hussein Abdullahi , Jackson Jemila , Baksh Amilah , Crutchley Jenany , Ellis Shani , Ma Yunfei
Published: June 2014

In this article, we present an innovative methodological use of physical objects in facilitating the construction and reconstruction of meaning in a qualitative social work research project exploring youth violence and healing among racial minority youth in Canada. To highlight the role of physical objects in making visible the intricate processes of meaning making and remaking, we provide a close-up view of a symbolic objects activity performed by members of a Research Advisory Group in one site of a larger multisite project. We discuss the implications for broader qualitative practices in social work.
The Expanding Role of School Nurses
Authors: Luffy Robin , Wagner Christine
Published: June 2014

Children with asthma are at risk of experiencing the effects of ozone on the respiratory system at a lower concentration than normal or with a greater morbidity. The North Texas Asthma Consortium partnered with the U.S. Environmental Protection Agency, the Department of Health and Human Services, and the Asthma Coalition of Texas to implement an ozone awareness program in schools in North Texas. The goal of the ozone awareness program was to introduce and support a process for schools to raise ozone awareness in the school and community. Schools participating in the program fly a green, yellow, orange, or red flag each day alerting students, school staff, parents, and community members about the ozone. Activities for an active indoor curriculum on high ozone days, education about asthma and the effect of ozone, tools for implementing the program, and flags were provided. The program has been presented to almost 250 schools with 85 schools participating.
New Insights Into Stages of Lyme Disease Symptoms From a Novel Hospital-Based Registry
Authors: Lobraico Jessika , Butler Amber , Petrini Joann , Ahmadi Ramin
Published: June 2014

Background: Western Connecticut Health Network created the Lyme Disease Registry in response to the community’s request and clinical need for more Lyme disease research. The registry includes acute, recovered, and persistently symptomatic patients to better define the different stages of the disease. The design of the registry was guided by community and clinician input through a community-based participatory research process. Methods: Registry participants are asked questions regarding their diagnosis, symptoms, treatments, recovery, and satisfaction with the Registry. A blood specimen is also collected and stored at the initial appointment. Results: The Lyme Disease Registry has enrolled 256 participants, 24% are acute cases, 45% are persistently symptomatic cases, and 31% are recovered cases. The symptoms experienced by the group of patients with persistent symptoms had unexpectedly strong overlap with those experienced by acutely infected patients. Conclusion: The difference between symptoms in the acutely infected patients and those experiencing persistent symptoms is not as large as initially thought.
Diabetes Knowledge, Health Belief, and Diabetes Management Among the Igala, Nigeria
Authors: Adejoh Samuel Ojima
Published: June 2014

The study examined the association and influence of diabetes knowledge and health beliefs on diabetes management among the Igala, Nigeria. Data were collected using a structured questionnaire administered to 152 respondents living with diabetes. The data were analyzed using SPSS. Almost half of the respondents had low diabetes knowledge. Significant relationship existed between level of diabetes knowledge and diabetes management (1, N = 152) = 8.456, p = .004. There was a significant positive relationship between perceived severity (0.549, p = .000), perceived benefits (12.383, p = .000), and diabetes management. The regression result showed that diabetes knowledge influenced diabetes management (β = .262, t = 3.328, p = .001) and health beliefs affected diabetes management (β = .07865, t = 2.439, p < .016). Although diabetes knowledge and health belief are cognitive factors in diabetes management, they should not be considered in isolation of other social factors.
Influence of chromium on microstructure and etching behaviour of new Ni–Fe–Al based alloy
Authors: Huttner F. , Necker M. , Rösler J.
Published: June 2014

In the present study, the influence of chromium on the microstructure and etching behaviour of the polycrystalline alloy Ni–13Fe–8Al–4Ti (at-) has been examined. The alloy was recently designed for nanomembrane fabrication, but although it showed the necessary γ/γ′ microstructure with cubic, well aligned γ′ precipitates, it proved to be unsuitable for nanomembrane fabrication as the γ matrix was dissolved during chemical etching. To obtain the passivation of the γ matrix, chromium has been added in further modifications containing 1, 2, 3 and 4 at- chromium. Moreover, the influence of heat treatment and the different cooling rates of heat treatment in air/vacuum have been investigated. For chemical phase extraction, the application of the chemical etchants MoO3 acid and ‘G’ etchant has been examined, the formability was characterised by Vickers hardness testing. The main purpose of the present study, namely the passivation of the γ matrix, could be achieved by the addition of 4 at- chromium and etching with ‘G’ etchant.
Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients
Authors: Neven Bénédicte , Bruneau Julie , Stolzenberg Marie-Claude , Meyts Isabelle , Magerus-Chatinet Aude , Moens Leen , Lanzarotti Nina , Weller Sandra , Amiranoff Denise , Florkin Benoit , Bader-Meunier Brigitte , Leverger Guy , Ferster Alice , Chantrain Christophe , Blanche Stéphane , Picard Capucine , Molina Thierry Jo , Brousse Nicole , Durandy Anne , Rizzi Marta , Bossuyt Xavier , Fischer Alain , Rieux-Laucat Frederic
Published: June 2014

Key Points

ALPS predisposes to invasive bacterial infections, notably following splenectomy, and is associated with defective B-cell function. Poor anti-polysaccharide IgM antibody production and spleen MZ disorganization correlate with lymphoproliferation.
Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia
Authors: Malcovati Luca , Papaemmanuil Elli , Ambaglio Ilaria , Elena Chiara , Gallì Anna , Della Porta Matteo G. , Travaglino Erica , Pietra Daniela , Pascutto Cristiana , Ubezio Marta , Bono Elisa , Da Vià Matteo C. , Brisci Angela , Bruno Francesca , Cremonesi Laura , Ferrari Maurizio , Boveri Emanuela , Invernizzi Rosangela , Campbell Peter J. , Cazzola Mario
Published: June 2014

Key Points

Different driver mutations have distinct effects on phenotype of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Accounting for driver mutations may allow a classification of these disorders that is considerably relevant for clinical decision-making.
Rac2 is involved in bleomycin-induced lung inflammation leading to pulmonary fibrosis
Authors: Arizmendi Narcy , Puttagunta Lakshmi , Chung Kerri L , Davidson Courtney , Rey-Parra Juliana , Chao Danny V , Thebaud Bernard , Lacy Paige , Vliagoftis Harissios
Published: June 2014

Background

Pulmonary fibrotic diseases induce significant morbidity and mortality, for which there are limited therapeutic options available. Rac2, a ras-related guanosine triphosphatase expressed mainly in hematopoietic cells, is a crucial molecule regulating a diversity of mast cell, macrophage, and neutrophil functions. All these cell types have been implicated in the development of pulmonary fibrosis in a variety of animal models. For the studies described here we hypothesized that Rac2 deficiency protects mice from bleomycin-induced pulmonary fibrosis.

Methods

To determine the role of Rac2 in pulmonary fibrosis we used a bleomycin-induced mouse model. Anesthetized C57BL/6 wild type and rac2

-/-
mice were instilled intratracheally with bleomycin sulphate (1.25 U/Kg) or saline as control. Bronchoalveolar lavage (BAL) samples were collected at days 3 and 7 of treatment and analyzed for matrix metalloproteinases (MMPs). On day 21 after bleomycin treatment, we measured airway resistance and elastance in tracheotomized animals. Lung sections were stained for histological analysis, while homogenates were analyzed for hydroxyproline and total collagen content.

Results

BLM-treated rac2

-/-
mice had reduced MMP-9 levels in the BAL on day 3 and reduced neutrophilia and TNF and CCL3/MIP-1α levels in the BAL on day 7 compared to BLM-treated WT mice. We also showed that rac2

-/-
mice had significantly lower mortality (30%) than WT mice (70%) at day 21 of bleomycin treatment. Lung function was diminished in bleomycin-treated WT mice, while it was unaffected in bleomycin-treated rac2

-/-
mice. Histological analysis of inflammation and fibrosis as well as collagen and hydroxyproline content in the lungs did not show significant differences between BLM-treated rac2

-/-
and WT and mice that survived to day 21.

Conclusion

Rac2 plays an important role in bleomycin-induced lung injury. It is an important signaling molecule leading to BLM-induced mortality and it also mediates the physiological changes seen in the airways after BLM-induced injury.
Decision tree model for predicting long-term outcomes in children with out-of-hospital cardiac arrest: a nationwide, population-based observational study
Authors: Goto Yoshikazu , Maeda Tetsuo , Nakatsu-Goto Yumiko
Published: June 2014

Introduction

At hospital arrival, early prognostication for children after out-of-hospital cardiac arrest (OHCA) might help clinicians formulate strategies, particularly in the emergency department. In this study, we aimed to develop a simple and generally applicable bedside tool for predicting outcomes in children after cardiac arrest.

Methods

We analyzed data of 5,379 children who had undergone OHCA. The data were extracted from a prospectively recorded, nationwide, Utstein-style Japanese database. The primary endpoint was survival with favorable neurological outcome (Cerebral Performance Category (CPC) scale categories 1 and 2) at 1 month after OHCA. We developed a decision tree prediction model by using data from a 2-year period (2008 to 2009, n = 3,693), and the data were validated using external data from 2010 (n = 1,686).

Results

Recursive partitioning analysis for 11 predictors in the development cohort indicated that the best single predictor for CPC 1 and 2 at 1 month was the prehospital return of spontaneous circulation (ROSC). The next predictor for children with prehospital ROSC was an initial shockable rhythm. For children without prehospital ROSC, the next best predictor was a witnessed arrest. Use of a simple decision tree prediction model permitted stratification into four outcome prediction groups: good (prehospital ROSC and initial shockable rhythm), moderately good (prehospital ROSC and initial nonshockable rhythm), poor (prehospital non-ROSC and witnessed arrest) and very poor (prehospital non-ROSC and unwitnessed arrest). By using this model, we identified patient groups ranging from 0.2% to 66.2% for 1-month CPC 1 and 2 probabilities. The validated decision tree prediction model demonstrated a sensitivity of 69.7% (95% confidence interval (CI) = 58.7% to 78.9%), a specificity of 95.2% (95% CI = 94.1% to 96.2%) and an area under the receiver operating characteristic curve of 0.88 (95% CI = 0.87 to 0.90) for predicting 1-month CPC 1 and 2.

Conclusions

With our decision tree prediction model using three prehospital variables (prehospital ROSC, initial shockable rhythm and witnessed arrest), children can be readily stratified into four groups after OHCA. This simple prediction model for evaluating children after OHCA may provide clinicians with a practical bedside tool for counseling families and making management decisions soon after patient arrival at the hospital.
Comparative assessment of plant protection products: how many cases will regulatory authorities have to answer?
Authors: Faust Michael , Vogs Carolina , Rotter Stefanie , Wöltjen Janina , Höllrigl-Rosta Andreas , Backhaus Thomas , Altenburger Rolf
Published: June 2014

Background

The substitution principle has been included in the EU pesticides legislation as a new element. Comparative assessments will have to be conducted for all uses of plant protection products (PPPs) that contain active substances with certain hazardous properties, the so-called candidates for substitution (CFS). This study investigated the resulting workload in terms of the number of cases for comparative assessments that regulatory authorities may have to face. The analysis was carried out for Germany as an example.

Main text

In Germany, the requirement for comparative assessments may affect up to 25% of all PPPs and around 50% of all uses of PPPs. In absolute terms, these are around 350 candidate products with 1,850 different uses. Alternative products without CFS may be available for around 40% of these uses. On average, a candidate product is authorised for around 18 different uses. For 11 of these uses, no alternatives are authorised. For the remaining seven uses, slightly more than seven alternatives are available on average. Multiplication of these factors gives an indicative figure of around 18,500 possible pairwise comparisons of candidate products with alternative products for every common use.

Conclusions

The high number of expectable cases poses a formidable challenge for the efficient conduct of the new task of comparative assessments by competent Member States authorities. To this end, new data handling systems, assessment procedures, and decision rules need to be established.
Editorial: (Micro)Plastics and the environment
Authors: Wagner Martin , Engwall Magnus , Hollert Henner
Published: June 2014

(Micro)Plastics in the aquatic environment are an issue of emerging concern. However, to date, there is considerable lack of knowledge on the abundance and toxicity of plastic debris in aquatic ecosystems, especially with regard to the freshwater situation. In this editorial, we briefly discuss important aspects of the research on environmental (micro)plastics to stimulate research and call for papers.
Phase field simulation of dendrite growth with boundary heat flux
Authors: Du Lifei , Zhang Rong
Published: June 2014

Boundary heat flux has a significant effect on solidification behavior and microstructure formation, for it can directly affect the interfacial heat flux and cooling rate during phase transition. In this study, a phase field model for non-isothermal solidification in binary alloys is employed to simulate the free dendrite growth in undercooled melts with induced boundary heat flux, and an anti-trapping current is introduced to suppress the solute trapping due to the larger interface width used in simulations than a real solidifying material. The effect of heat flux input/extraction from different boundaries was studied first. With heat input from boundaries, the temperature can be raised and the dendritic morphology changed with gradient temperature distribution caused by the heat flux input coupling with latent heat release during the liquid-solid phase transition. Also, the concentration distribution can be also influenced by this irregular temperature distribution. Heat flux extraction from the boundaries can decrease the temperature, which results in rapid solidification with small solute segregation and concentration changes in the dendrite structures. Also, dendrite growth manner changes caused by undercooling variation, the result of competition between heat flux and latent heat release from phase transition, are also studied. Results indicate that heat flux in the simulation zone significantly reduces the undercooling, thus slowing down the dendrite formation and enhancing the solute segregation, while large heat extraction can enlarge the undercooling and lead to rapid solidification with large dendrite tip speed and small secondary dendrite arm spacing, while solute segregation tends to be steady. Therefore, the boundary heat flux coupling with the latent heat release from the solidification has an effective influence on the temperature gradient distribution within the simulation zone, which leads to the morphology and concentration changes in the dendritic structure formation.
HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells
Authors: Stone Simone Cardozo , Rossetti Renata Ariza Marques , Bolpetti Aline , Boccardo Enrique , de Araujo Souza Patricia Savio , Lepique Ana Paula
Published: June 2014

Tumors are complex structures containing different types of cells and molecules. The importance of the tumor microenvironment in tumor progression, growth, and maintenance is well-established. However, tumor effects are not restricted to the tumor microenvironment. Molecules secreted by, as well as cells that migrate from tumors, may circulate and reach other tissues. This may cause a series of systemic effects, including modulation of immune responses, and in some cases, leukocytosis and metastasis promotion. Leukocytosis has been described as a poor prognostic factor in patients with cervical cancer. The main etiological factor for cervical cancer development is persistent infection with high oncogenic risk HPV. Our laboratory has been exploring the effects of high oncogenic risk, HPV-associated tumors on lymphoid organs of the host. In the present study, we observed an increase in myeloid cell proliferation and alteration in cell signaling in APCs in the spleen of tumor-bearing mice. In parallel, we characterized the cytokines secreted in the inflammatory and tumor cell compartments in the tumor microenvironment and in the spleen of tumor-bearing mice. We show evidence of constitutive activation of the IL-6/STAT3 signaling pathway in the tumor, including TAMs, and in APCs in the spleen. We also observed that IL-10 is a central molecule in the tolerance toward tumor antigens through control of NF-κB activation, costimulatory molecule expression, and T cell proliferation. These systemic effects over myeloid cells are robust and likely an important problem to be addressed when considering strategies to improve anti-tumor T cell responses.
Cancer incidence in people with affective disorder: nationwide
cohort study in Taiwan, 1997–2010
Authors: Hung Yen-Ni , Yang Shu-Yu , Huang Ming-Chyi , Lung For-Wey , Lin Shih-Ku , Chen Kuan-Yu , Kuo Chian-Jue , Chen Ying-Yeh
Published: June 2014

Background

Cancer is a serious public health problem worldwide, and its relationship
with affective disorders is not clear.

Aims

To investigate alcohol- and tobacco-related cancer risk among patients
with affective disorders in a large Taiwanese cohort.

Method

Records of newly admitted patients with affective disorders from January
1997 through December 2002 were retrieved from the Psychiatric Inpatient
Medical Claims database in Taiwan. Cancers were stratified by site and
grouped into tobacco- or alcohol-related cancers. Standardised incidence
ratios (SIRs) were calculated to compare the risk of cancer between those
with affective disorders and the general population.

Results

Some 10 207 patients with bipolar disorder and 9826 with major depression
were included. The risk of cancer was higher in patients with major
depression (SIR = 2.01, 95% CI 1.85–2.19) than in those with bipolar
disorder (SIR 1.39, 95% CI 1.26–1.53). The elevated cancer risk among
individuals ever admitted to hospital for affective disorders was more
pronounced in tobacco- and/or alcohol-related cancers.

Conclusions

Elevated cancer risk was found in patients who had received in-patient
care for affective disorders. They require holistic approaches to
lifestyle behaviours and associated cancer risks.
The SMRT Coregulator Enhances Growth of Estrogen Receptor-α-Positive Breast Cancer Cells by Promotion of Cell Cycle Progression and Inhibition of Apoptosis
Authors: Blackmore Julia K. , Karmakar Sudipan , Gu Guowei , Chaubal Vaishali , Wang Liguo , Li Wei , Smith Carolyn L.
Published: June 2014

The SMRT coregulator functions as a dual coactivator and corepressor for estrogen receptor-α (ERα) in a gene-specific manner, and in several studies its elevated expression correlates with poor outcome for breast cancer patients. A specific role of SMRT in breast cancer progression has not been elucidated, but SMRT knock-down limits estradiol-dependent growth of MCF-7 breast cancer cells. In this study, small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) approaches were used to determine the effects of SMRT depletion on growth of ERα-positive MCF-7 and ZR-75–1 breast cancer cells, as well as the ERα-negative MDA-MB-231 breast cancer line. Depletion of SMRT inhibited growth of ERα-positive cells grown in monolayer but had no effect on growth of the ERα-negative cells. Reduced SMRT levels also negatively impacted the anchorage-independent growth of MCF-7 cells as assessed by soft agar colony formation assays. The observed growth inhibitions were due to a loss of estradiol-induced progression through the G1/S transition of the cell cycle and increased apoptosis in SMRT-depleted compared with control cells. Gene expression analyses indicated that SMRT inhibits apoptosis by a coordinated regulation of genes involved in apoptosis. Functioning as a dual coactivator for anti-apoptotic genes and corepressor for pro-apoptotic genes, SMRT can limit apoptosis. Together these data indicate that SMRT promotes breast cancer progression through multiple pathways leading to increased proliferation and decreased apoptosis.
Functional Characterization of Obesity-Associated Variants Involving the α and β Isoforms of Human SH2B1
Authors: Pearce Laura R. , Joe Ray , Doche Michael E. , Su Hsiao-Wen , Keogh Julia M. , Henning Elana , Argetsinger Lawrence S. , Bochukova Elena G. , Cline Joel M. , Garg Sumedha , Saeed Sadia , Shoelson Steven , O'Rahilly Stephen , Barroso Inês , Rui Liangyou , Farooqi I. Sadaf , Carter-Su Christin
Published: June 2014

We have previously reported rare variants in sarcoma (Src) homology 2 (SH2) B adaptor protein 1 (SH2B1) in individuals with obesity, insulin resistance, and maladaptive behavior. Here, we identify 4 additional SH2B1 variants by sequencing 500 individuals with severe early-onset obesity. SH2B1 has 4 alternatively spliced isoforms. One variant (T546A) lies within the N-terminal region common to all isoforms. As shown for past variants in this region, T546A impairs SH2B1β enhancement of nerve growth factor-induced neurite outgrowth, and the individual with the T546A variant exhibits mild developmental delay. The other 3 variants (A663V, V695M, and A723V) lie in the C-terminal tail of SH2B1α. SH2B1α variant carriers were hyperinsulinemic but did not exhibit the behavioral phenotype observed in individuals with SH2B1 variants that disrupt all isoforms. In in vitro assays, SH2B1α, like SH2B1β, enhances insulin- and leptin-induced insulin receptor substrate 2 (IRS2) phosphorylation and GH-induced cell motility. None of the variants affect SH2B1α enhancement of insulin- and leptin-induced IRS2 phosphorylation. However, T546A, A663V, and A723V all impair the ability of SH2B1α to enhance GH-induced cell motility. In contrast to SH2B1β, SH2B1α does not enhance nerve growth factor-induced neurite outgrowth. These studies suggest that genetic variants that disrupt isoforms other than SH2B1β may be functionally significant. Further studies are needed to understand the mechanism by which the individual isoforms regulate energy homeostasis and behavior.