bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Postnatal Acquisition of the Intestinal Microbiome in the Early Development of Immune Function
Authors: Dimmitt Reed A , Staley Elizabeth M , Chuang Gin , Tanner Scott M , Soltau Thomas D , Lorenz Robin G
Published: July 2010

Objectives:

Therapy with broad‐spectrum antibiotics is a common practice for premature infants. This treatment can reduce the biodiversity of the fecal microbiota and may be a factor in the cause of necrotizing enterocolitis. In contrast, probiotic treatment of premature infants reduces the incidence of necrotizing enterocolitis. We hypothesized that 1 mechanism for these observations is the influence of bacteria on postnatal development of the mucosal immune system.

Materials and Methods:

Expression of immune molecules and microbial sensors was investigated in the postnatal mouse gastrointestinal tract by real‐time polymerase chain reaction. Subsequently, 2‐week‐old specific pathogen‐free and microbial‐reduced (MR; antibiotic treated) mice were compared for immune molecule and microbial sensor expression, mesenteric lymph node T‐cell numbers and activation, intestinal barrier function/permeability, systemic lymphocyte numbers, and T‐cell phenotype commitment.

Results:

Toll‐like receptor 2, 4, and 5 expression was highest in 2‐week‐old specific pathogen‐free mice, and this expression was decreased in MR mice. There was no difference in intestinal tight‐junctional function, as evaluated by fluorescein isothiocyanate‐dextran uptake, but MR mice had increased bacterial translocation across the intestinal epithelial barrier. MR mice had significantly fewer splenic B cells and mesenteric lymph node CD4+ T cells, but there were normal numbers of splenic T cells. These systemic T cells from MR mice produced more interleukin‐4 and less interferon‐γ and IL‐17, indicative of maintenance of the fetal, T‐helper cell type 2 phenotype.

Conclusions:

The present study shows that intestinal commensal microbiota have an influence on early postnatal immune development. Determining specific bacteria and/or bacterial ligands critical for this development could provide insight into the mechanisms by which broad‐spectrum antibiotics and/or probiotic therapy influence the development of the mucosal immune system and mucosal‐related diseases.
Munchausen Syndrome by Proxy: Ongoing Clinical Challenges
Authors: Squires Janet E , Squires Robert H
Published: July 2010

In 1977, Roy Meadow, a pediatric nephrologist, first described a condition he subsequently coined Munchausen syndrome by proxy. The classic form involves a parent or other caregiver who inflicts injury or induces illness in a child, deceives the treating physician with fictitious or exaggerated information, and perpetrates the trickery for months or years. A related form of pathology is more insidious and more common but also damaging. It involves parents who fabricate or exaggerate symptoms of illness in children, causing overly aggressive medical evaluations and interventions. The common thread is that the treating physician plays a role in inflicting the abuse upon the child. Failure to recognize the problem is common because the condition is often not included in the differential diagnosis of challenging or confusing clinical problems. We believe that a heightened “self‐awareness” of the physician's role in Munchausen syndrome by proxy will prevent or reduce the morbidity and mortality associated with this diagnosis. In addition, we believe contemporary developments within the modern health care system likely facilitate this condition.
In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates
Authors: Ahmad Aijaz , Khan Amber , Khan Luqman Ahmad , Manzoor Nikhat
Published: July 2010

The speciesCandidais a group of opportunistic pathogenic commensals in immune-compromised patients. Treatment ofCandidainfections is becoming increasingly difficult due to antifungal drug resistance, especially with fluconazole (FLC), which is a commonly used azole. In the present study thein vitroantifungal activity of eugenol (EUG) and methyleugenol (MEUG) alone and in combination against 64 FLC-sensitive and 34 FLC-resistant clinicalCandidaisolates is highlighted. All the strains were susceptible to both the naturally occurring phenyl propanoids. The nature of the interaction was studied from fractional inhibitory concentration indices (FICIs) for both EUG plus FLC, and MEUG plus FLC combinations calculated from chequerboard microdilution assays. FICI values depicted a high synergism of FLC with both compounds, which was greatest with MEUG. FLC-resistantCandidaisolates showed high sensitivity to both compounds. No antagonistic activity was seen in the strains tested in the present study. From these results we suggest that EUG and MEUG have great potential as antifungals, and that FLC can be supplemented with EUG and MEUG to treat FLC-resistantCandidainfections.
Bacillus subtilis mutants harbouring a single copy of the rRNA operon exhibit severe defects in growth and sporulation
Authors: Nanamiya Hideaki , Sato Makiko , Masuda Kenta , Sato Mikiko , Wada Tetsuya , Suzuki Shota , Natori Yousuke , Katano Masato , Akanuma Genki , Kawamura Fujio
Published: July 2010

The number of copies of rRNA genes in bacterial genomes differs greatly among bacterial species. It is difficult to determine the functional significance of the heterogeneity of each rRNA operon fully due to the existence of multiple rRNA operons and because the sequence heterogeneity among the rRNA genes is extremely low. To overcome this problem, we sequentially deleted the tenrrnoperons ofBacillus subtilisand constructed seven mutant strains that each harboured a singlerrnoperon (eitherrrnA,B,D,E,I,JorO) in their genome. The growth rates and sporulation frequencies of these mutants were reduced drastically compared with those of the wild-type strain, and this was probably due to decreased levels of ribosomes in the mutants. Interestingly, the ability to sporulate varied significantly among the mutant strains. These mutants have proved to be invaluable in our initial attempts to reveal the functional significance of the heterogeneity of each rRNA operon.
A Metabolomic Approach to Study Major Metabolite Changes during Acclimation to Limiting CO2 in Chlamydomonas reinhardtii
Authors: Renberg Linda , Johansson Annika I. , Shutova Tatiana , Stenlund Hans , Aksmann Anna , Raven John A. , Gardeström Per , Moritz Thomas , Samuelsson Göran
Published: July 2010

Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high- and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.
Global genomic and RNA profiles for novel risk stratification of neuroblastoma
Authors: Ohira Miki , Nakagawara Akira
Published: July 2010

Neuroblastoma is one of the most common solid tumors in children. Its clinical behavior ranges widely from spontaneous regression to life‐threatening aggressive growth. The molecular etiology of neuroblastoma is still enigmatic and the overall cure rate of advanced disease is still very poor. Recent microarray‐based technology provided us with important information such as comprehensive genomic alterations and gene expression profiles to help us understand the molecular characteristics of each tumor in detail. Several retrospective studies have revealed that these signatures are strongly correlated with patient prognoses and led to the construction of new risk stratification systems, some of which are considered for evaluation in upcoming clinical studies in a prospective way. Large‐scale analyses using a variety of genetic tools also discovered a major familial neuroblastoma predisposition gene ALK, as well as new candidate susceptibility genes at 6q22 and 2q35 for sporadic neuroblastoma. Of note, ALK is mutated in 6–9% of sporadic cases, and is either amplified or constitutively activated through mutations mainly within the kinase domain, promoting the possibility of new therapeutic strategies using ALK inhibitors. Additional candidates for outcome predictors such as the methylation phenotype of tumor DNA and expression profiles of microRNA have also been proposed. Such variety of information will help us understand the heterogeneity of neuroblastoma biology and further, the combined use of these signatures will be beneficial in predicting prognosis with high accuracy, as well as choosing a suitable therapy for the individual patient. (Cancer Sci 2010; 101: 2295–2301)
Review article: lymphatic system and associated adipose tissue in the development of inflammatory bowel disease
Authors: Von Der Weid P.‐Y. , Rainey K. J.
Published: July 2010

Background The lymphatic system plays critical roles in tissue fluid homoeostasis, immune defence and metabolic maintenance. Lymphatic vessels transport lymph, proteins, immune cells and digested lipids, allowing fluid and proteins to be returned to the blood stream, lipids to be stored and metabolized and antigens to be sampled in lymph nodes. Lymphatic drainage is mainly driven by rhythmic constrictions intrinsic to the vessels and critically modulated by fluid pressure and inflammatory mediators.

Aim To collect and discuss the compelling available information linking the lymphatic system, adiposity and inflammation.

Methods A literature search was performed through PubMed focusing on lymphatic system, inflammation, immune cells and fat transport and function in the context of IBD.

Results Evidence collected allows us to propose the following working model. Compromised lymph drainage, reported in IBD, leads to oedema, lymphangiogenesis, impaired immune cell trafficking and lymph leakage. Lymph factor(s) stimulate adipose tissue to proliferate and produce cytokines, which affect immune cell functions and exacerbate inflammation.

Conclusions Understanding the lymphatic system’s role in immune cell trafficking and immune responses, contribution to fat transport, distribution, metabolism and implication in the pathogenesis of chronic intestinal inflammation may provide the basis for new therapeutic strategies and improved quality‐of‐life.
Children with atopic histories exhibit impaired lipopolysaccharide‐induced Toll‐like receptor‐4 signalling in peripheral monocytes
Authors: Préfontaine D. , Banville‐Langelier A.‐A. , Fiset P.‐O. , Guay J. , An J. , Mazer M. , Hamid Q. , Mazer B. D.
Published: July 2010

Background
The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll‐like receptor (TLR)‐4 on CD4+ cells in nasal mucosa.

Objective
To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4+ leucocytes.

Methods
Peripheral blood mononuclear cells from children (aged 2–18) and adults with or without a history of atopic conditions were cultured with/without IL‐4 or LPS for up to 24 h. Expression of surface TLR‐4, CD14, CD4, CD3, as well as of intracellular phosphorylated p42/p44ERK and p38 mitogen‐activated protein kinase (MAPK) were assessed by flow cytometry.

Results
A history of atopy in children was associated with impaired LPS‐induced TLR‐4‐dependent phosphorylation of p42/44ERK and p38 MAPK by CD4+ monocytes. Decreased LPS signalling was reproduced by pre‐incubation of control cells with recombinant IL‐4. LPS stimulation also decreased TLR‐4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4+ T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non‐atopic children, TLR‐4 expression on monocytes of children with atopic histories decreased as a function of age.

Conclusions
This study provides evidence for defective LPS recognition on circulating CD4+ leucocytes of subjects with atopic histories compared with those from non‐atopic children. CD4+TLR4+ monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR‐4‐mediated innate immune function compared with non‐atopic children.

Cite this as: D. Préfontaine, A.‐A. Banville‐Langelier, P.‐O. Fiset, J. Guay, J. An, M. Mazer, Q. Hamid and B. D. Mazer, Clinical & Experimental Allergy, 2010 (40) 1648–1657.
Socio‐economic status, geographic remoteness and childhood food allergy and anaphylaxis in Australia
Authors: Mullins R. J. , Clark S. , Camargo C. A.
Published: July 2010

Background
The risk factors for food allergy (FA) and anaphylaxis remain uncertain.

Objective
We examined the association between socio‐economic status (SES), geographic remoteness and childhood FA and anaphylaxis in Australia.

Methods
Sales of infant hypoallergenic formulae (IHF; 2008–2009) and EpiPens (2006–2007) in children aged 0–4 years and hospital anaphylaxis admission rates (2002–2006) in age groups 0–4, 5–14, 15–24, 25–64 and 65+ years were used as proxy markers of FA and anaphylaxis in Australia. Government and commercially derived data were analysed by SES and geographic remoteness (very remote, remote, outer regional, inner regional and major cities).

Results
Annual IHF sales rates were higher in those with the greatest compared with the least socio‐economic advantage (47 830 vs. 21 384 tins/100 000 population; P<0.001). EpiPen sales trends were also higher in those with the greatest socio‐economic advantage in all age groups, most marked in those aged 0–4 (1713 vs. 669/100 000; P=0.002) and 5–14 years (1628 vs. 600/100 000; P=0.001). Formula sales rates were higher in major cities than remote/very remote regions (37 421 vs. 6704/100 000; P<0.001) with similar EpiPen sales trends, particularly in ages 0–4 (1166 vs. 601/100 000; P=0.045) and 5–14 years (1099 vs. 588/100 000; P<0.001). Socio‐economic advantage and geographic remoteness remained statistically significant in multivariable analysis of prescription rates (P<0.01) and were unchanged by adjustment for health services access. While anaphylaxis admission rates were higher in those with the greatest compared with the least socio‐economic advantage in children aged 0–4 years (129 vs. 92/100 000 population/year; P=0.03), the opposite was observed in older age groups (e.g. aged 25–64 years: 43 vs. 76, P=0.01). There was no association between geographic remoteness and anaphylaxis admissions.

Conclusion
Socio‐economic advantage and residence in major cities may be risk factors for developing childhood FA and anaphylaxis. Further study will determine the extent to which economic factors and location of residence also influence access to health services.

Cite this as: R. J. Mullins, S. Clark and C. A. Camargo Jr., Clinical & Experimental Allergy, 2010 (40) 1523–1532.
Circulating CD14+CD16+ monocyte levels predict tissue invasive character of cholangiocarcinoma
Authors: Subimerb C , Pinlaor S , Lulitanond V , Khuntikeo N , Okada S , McGrath M S , Wongkham S
Published: July 2010

Chronic inflammation as a risk factor for cancer development is driven in part by monocyte/macrophages, which in many cancers exhibit pro-tumorigenic activity. In this study we identified elevation in CD14+CD16+, a minor blood monocyte subpopulation in cholangiocarcinoma (CCA) patients, compared to normal and biliary disease patient specimens. Tumour association was suggested by the observation that this elevated level decreased to normal after tumour resection. Moreover, the elevated level of CD14+CD16+ monocytes in CCA patient blood correlated with degree of MAC387-positive (recent blood-derived macrophage migrant-specific marker) tumour-associated macrophage infiltration as determined by immunohistochemistry. These CD14+CD16+ monocytes were suggested to enhance tumour progression as this subpopulation possesses (i) high expression of adhesion molecules (CD11c, CD49d, and CD54) and scavenger receptor (CD163), which enable them to adhere strongly to endothelial cells, and (ii) that peripheral blood monocytes from CCA patients express high levels of growth and angiogenic factor-related genes (epiregulin, VEGF-A and CXCL3). Elevation of peripheral CD14+CD16+ monocyte levels was associated with features associated with poor prognosis CCA parameters (non-papillary type and high number of tissue macrophages). These data indicate that the CD14+CD16+ monocytes from CCA patients with pro-tumorigenic characteristics may associate with rapid tumour progression and poor patient outcome. If confirmed in subsequent studies, the level of CD14+CD16+ monocytes may serve as a marker for disease activity in CCA patients and serve as a target for pathogenic macrophage specific drug development.
Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases
Authors: Marzano A V , Cugno M , Trevisan V , Fanoni D , Venegoni L , Berti E , Crosti C
Published: July 2010

Pyoderma gangrenosum (PG) is a rare, immune-mediated inflammatory skin disease presenting with painful ulcers having undermined edges. Less commonly, bullous and vegetative variants exist. Histology consists of a neutrophil-rich dermal infiltrate. We characterized immunohistochemically the infiltrate in different variants of PG and in another neutrophilic dermatosis as Sweet's syndrome. We studied 21 patients with PG, eight with Sweet's syndrome and 20 controls, evaluating skin immunoreactivity for inflammatory cell markers (CD3, CD163 and myeloperoxidase), cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-8 and IL-17], metalloproteinases (MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF). Immunoreactivities of CD3, CD163, myeloperoxidase, TNF-α, IL-8, IL-17, MMP-2, MMP-9 and VEGF were significantly higher in both PG and Sweet's syndrome than in controls (P = 0·0001). Myeloperoxidase (neutrophil marker), IL-8 (cytokine chemotactic for neutrophils) and MMP-9 (proteinase-mediating tissue damage) were expressed more significantly in both ulcerative and bullous PG than in vegetative PG as well as in Sweet's syndrome (P = 0·008–P = 0·0001). In ulcerative PG, the expression of CD3 (panT cell marker) and CD163 (macrophage marker) were significantly higher in wound edge than wound bed (P = 0·0001). In contrast, the neutrophil marker myeloperoxidase was expressed more significantly in wound bed than wound edge (P = 0·0001). Our study identifies PG as a paradigm of neutrophil-mediated inflammation, with proinflammatory cytokines/chemokines and MMPs acting as important effectors for the tissue damage, particularly in ulcerative and bullous PG where damage is stronger. In ulcerative PG, the wound bed is the site of neutrophil-recruitment, whereas in the wound edge activated T lymphocytes and macrophages pave the way to ulcer formation.
A critical update on the immunopathogenesis of Stiff Person Syndrome
Authors: Alexopoulos Harry , Dalakas Marinos C.
Published: July 2010

Eur J Clin Invest 2010; 40 (11): 1018–1025

Background  Stiff Person Syndrome (SPS) is a relatively rare but often overlooked autoimmune neurological disorder that targets antigens within the brain’s inhibitory pathways resulting in incapacitating stiffness and spasms that impact on the patients’ quality of life. Although a number of immunomodulating therapies significantly improve the patients’ symptoms, the exact pathogenic mechanisms remain unclear.

Materials and methods  The current literature on SPS was reviewed and combined with the authors' experience with many patients and various laboratory studies. The majority of the patients have high‐titre anti‐GAD (Glutamic Acid Decarboxylase) antibodies in the sera and CSF suggesting dysfunction of the GABAergic neurotransmission. These antibodies are excellent disease markers but their pathogenic role remains uncertain.

Conclusions  This review provides a critical assessment on the immunobiology of SPS, describes the identification of anti‐GABARAP antibodies as a new antigenic target in the GABAergic synapse and identifies the areas for future research.
A critical function of toll‐like receptor‐3 in the induction of anti‐human immunodeficiency virus activities in macrophages
Authors: Zhou Yu , Wang Xu , Liu Manqing , Hu Quan , Song Li , Ye Li , Zhou Dunjin , Ho Wenzhe
Published: July 2010

Toll‐like receptor‐3 (TLR‐3) recognizes double‐stranded RNA and induces multiple intracellular events responsible for innate anti‐viral immunity against a number of viral infections. Activation of TLR‐3 inhibits human immunodeficiency virus (HIV) replication, but the mechanism(s) underlying the action of TLR‐3 activation on HIV are largely unknown. Here we demonstrate that treatment of monocyte‐derived macrophages with poly I:C, a synthetic ligand for TLR‐3, significantly inhibited HIV infection and replication. Investigation of the mechanisms showed that TLR‐3 activation resulted in the induction of type I interferon inducible antiviral factors, including APOBEC3G and tetherin, the newly identified anti‐HIV cellular proteins. In addition, poly I:C‐treated macrophages expressed increased levels of CC chemokines, the ligands for CCR5. Furthermore, TLR‐3 activation in macrophages induced the expression of cellular microRNAs (miRNA‐28, ‐125b, ‐150, ‐223 and ‐382), the newly identified intracellular HIV restriction factors. These findings indicate that TLR‐3‐mediated induction of multiple anti‐HIV factors should be beneficial for the treatment of HIV disease where innate immune responses are compromised by the virus.
The work of nurse practitioners
Authors: Gardner Glenn , Gardner Anne , Middleton Sandy , Della Phillip , Kain Victoria , Doubrovsky Anna
Published: July 2010

gardner g., gardner a., middleton s., della p., kain v. & doubrovsky a. (2010) The work of nurse practitioners.Journal of Advanced Nursing 66(10), 2160–2169.

Aim. This paper is a report of a study of variations in the pattern of nurse practitioner work in a range of service fields and geographical locations, across direct patient care, indirect patient care and service‐related activities.

Background. The nurse practitioner role has been implemented internationally as a service reform model to improve the access and timeliness of health care. There is a substantial body of research into the nurse practitioner role and service outcomes, but scant information on the pattern of nurse practitioner work and how this is influenced by different service models.

Methods. We used work sampling methods. Data were collected between July 2008 and January 2009. Observations were recorded from a random sample of 30 nurse practitioners at 10‐minute intervals in 2‐hour blocks randomly generated to cover 2 weeks of work time from a sampling frame of 6 weeks.

Results. A total of 12,189 individual observations were conducted with nurse practitioners across Australia. Thirty individual activities were identified as describing nurse practitioner work, and these were distributed across three categories. Direct care accounted for 36·1% of how nurse practitioners spend their time, indirect care accounted for 32·0% and service‐related activities made up 31·9%.

Conclusion. These findings provide useful baseline data for evaluation of nurse practitioner positions and the service effect of these positions. However, the study also raises questions about the best use of nurse practitioner time and the influences of barriers to and facilitators of this model of service innovation.
Child sexual abuse: is it a risk factor for pregnancy?
Authors: Yampolsky Lee , Lev‐Wiesel Rachel , Ben‐Zion Itzahk Z.
Published: July 2010

yampolsky l., lev‐wiesel r. & ben‐zion i.z.
(2010) Child sexual abuse: is it a risk factor for pregnancy? Journal of Advanced Nursing 66(9), 2025–2037.

Aim.  This paper is a report of a study of the relationship of post‐traumatic stress symptoms, depression, and health status to high risk pregnancy status in survivors of childhood sexual abuse.

Background.  Studies examining the long‐term effects of childhood sexual abuse have delineated diverse psychological, cognitive, and social difficulties in adult survivors that often manifest somatically.

Methods.  A random sample of 1835 mid‐pregnant Jewish women was recruited in Israel over an 18‐month period in 2005–2007. Participants were divided into three sub‐groups consisting of the different combinations between pregnancy at risk (yes/no), childhood sexual abuse (yes/no), other than childhood sexual abuse trauma (yes no), and no trauma (yes/no). They completed a self‐administered questionnaire consisting of five scales: a demographic variables scale, the Post‐traumatic Stress Disorder Symptom Scale, Center for Epidemiologic Studies Depression Scale, Traumatic Events Questionnaire, and Childhood Sexual Experiences Scale.

Findings.  Pregnant survivors of childhood sexual abuse suffered higher distress levels which heightened poor health, hence increasing the probability of high risk pregnancy compared to women who had had other than sexual abuse trauma or reported no trauma. Post traumatic stress symptoms and avoidance (a sub‐category) were found to explain chronic illnesses, whereas depression was found to explain gynecological problems in pregnant sexually‐abused survivors.

Conclusion.  Healthcare workers need to recognize and address the psychological state of pregnant child sexual abuse survivors. Screening of pregnant women for child sexual abuse is needed to assess survivors’ psychological well‐being and recognize their unique concerns during pregnancy monitoring.
Predicting nursing turnover with catastrophe theory
Authors: Wagner Cheryl M.
Published: July 2010

wagner c.m. (2010) Predicting nursing turnover with catastrophe theory. Journal of Advanced Nursing 66(9), 2071–2084.

Aim.  This paper is a report of a study comparing an innovative nonlinear model and a traditional linear model for accuracy in prediction of nursing turnover.

Background.  An international, sustained nursing shortage creates a need to target accurately the staff population at risk for turnover. Existing linear methodology is cumbersome with the number of variables needed, while producing inadequate results. Nonlinear modelling methods offer increased simplicity and accuracy in predictability.

Methods.  A correlational survey with a longitudinal cohort prospective study was carried out in 2005–2006 with a convenience sample of 1033 Registered Nurses from the Midwest region of the United States of America. At time 1, 756 usable questionnaires were returned and 496 at time 2. Data analysis included analyses of a cusp catastrophe model, a cube‐shaped four‐dimensional figure with a top that provided a down‐turning slope area (the catastrophe/cusp zone). This fluid, dynamic cusp version employed the smallest number of control and dependent variables.

Results.  The exceedingly small turnover sample preempted the use of the computerized program Cuspfit; a proven quasi‐quantitative methodology demonstrated 80·4% predictability in the cusp catastrophe model overall and 53·6% correct predictions of actual terminations, particularly in nurses with <5 years of nursing experience. Additional accurate predictions were obtained with the use of a time‐staged model. Organizational commitment and anticipated turnover were accurate predictor variables; job tension was not.

Conclusion.  Catastrophe models are useful in predicting nursing turnover. Future nursing researchers should act on this evidence to benefit forthcoming studies and the profession.
Against all odds: Australian women’s experiences of recovery from breast cancer
Authors: Elmir Rakime , Jackson Debra , Beale Barbara , Schmied Virginia
Published: July 2010

Aim.  The aim of this study was to generate insight into younger women’s experiences of recovery from breast cancer‐related breast surgery and to contribute to the knowledge base for clinicians practising in this field.

Background.  Despite the abundance of literature concerning the impact of breast cancer and breast loss on older women over 50 years of age, fewer studies have been conducted specifically with women younger than 50 years focusing on the recovery from breast cancer and related breast surgery. The effects of breast cancer on younger women differ to those of older women; younger women may have difficulty coming to terms with loss of fertility, perceived loss of femininity, sexuality and may experience body image disfigurement. Younger women may face these issues as a result of the treatment and surgery they have received to confine the breast cancer and attempt to improve their chances of survival.

Design.  A phenomenological qualitative methodology was used to capture the true essence and lived experience of four Australian women under the age of 50, who had undergone surgery as a result of being diagnosed with breast cancer.

Methods.  Tape‐recorded semi‐structured face‐to‐face interviews.

Results.  Thematic analysis revealed four major themes. These were ‘It absolutely encompassed me,’‘Being overwhelmed,’‘Living with fear and uncertainty’ and ‘Finding strength within.’

Conclusions.  Findings of this study shed light on the experiences of recovery from breast cancer‐related surgery in women under 50.

Relevance to clinical practice.  This research study will assist clinicians in understanding the needs of younger women undergoing breast cancer‐related breast surgery, who may require counselling in relation to fertility and relationship issues and assistance in coping with the demands of work and home life.
Adaptive assessment of student's knowledge in programming courses
Authors: Chatzopoulou D.I. , Economides A.A.
Published: July 2010

This paper presents Programming Adaptive Testing (PAT), a Web‐based adaptive testing system for assessing students' programming knowledge. PAT was used in two high school programming classes by 73 students. The question bank of PAT is composed of 443 questions. A question is classified in one out of three difficulty levels. In PAT, the levels of difficulties are adapted to Bloom's taxonomy lower levels, and students are examined in their cognitive domain. This means that PAT has been designed according to pedagogical theories in order to be appropriate for the needs of the course ‘Application Development in a Programming Environment’. If a student answers a question correctly, a harder question is presented, otherwise an easier one. Easy questions examine the student's knowledge, while difficult questions examine the student's skills to apply prior knowledge to new problems. A student answers a personalized test composed of 30 questions. PAT classifies a student in one out of three programming skills' levels. It can predict the corresponding classification of students in Greek National Exams. Furthermore, it can be helpful to both students and teachers. A student could discover his or her programming shortcomings. Similarly, a teacher could objectively assess his or her students as well as discover the subjects that need to be repeated.
Guiding students to the right questions: adaptive navigation support in an E‐Learning system for Java programming
Authors: Hsiao I.‐H. , Sosnovsky S. , Brusilovsky P.
Published: July 2010

Rapid growth of the volume of interactive questions available to the students of modern E‐Learning courses placed the problem of personalized guidance on the agenda of E‐Learning researchers. Without proper guidance, students frequently select too simple or too complicated problems and ended either bored or discouraged. This paper explores a specific personalized guidance technology known as adaptive navigation support. We developed JavaGuide, a system, which guides students to appropriate questions in a Java programming course, and investigated the effect of personalized guidance a three‐semester long classroom study. The results of this study confirm the educational and motivational effects of adaptive navigation support.
Sleep disturbances and behavioural problems in adults with Prader–Willi syndrome
Authors: Maas A. P. H. M. , Sinnema M. , Didden R. , Maaskant M. A. , Smits M. G. , Schrander‐Stumpel C. T. R. M. , Curfs L. M. G.
Published: July 2010

Background  Individuals with Prader–Willi syndrome (PWS) are at risk of sleep disturbances, such as excessive daytime sleepiness (EDS) and sleep apnoea, and behavioural problems. Sleep disturbances and their relationship with other variables had not been researched extensively in adults with PWS.

Method  Sleep disturbances and behavioural problems were investigated in adults with genetically confirmed PWS using standardised questionnaires. Results of adults with paternal deletion (n = 45) were compared with those of adults with maternal uniparental disomy (n = 33).

Results  Eleven adults with PWS (i.e. 15%) had a current sleep problem, mostly night waking problems. Twenty‐six adults with PWS (i.e. 33%) suffered from severe EDS. No differences in prevalence of sleep disturbances between genetic subtypes were found. Seventeen adults with deletion (i.e. 38%) and 17 adults with maternal uniparental disomy (i.e. 52%) had behavioural problems. No significant relationships were found between sleep disturbances and behavioural problems.

Conclusions  In adults with PWS, EDS is the most common type of sleep disturbance. Men and individuals with relative high body mass index are at increased risk for EDS. More research, aimed at developing a suitable screening instrument for sleep apnoea in adults with PWS, is necessary. Clinical implications of the findings are discussed.
Multistage dolomitization and distribution of dolomitized bodies in Early Jurassic carbonate platforms (Southern Alps, Italy)
Authors: RONCHI PAOLA , JADOUL FLAVIO , CERIANI ANDREA , DI GIULIO ANDREA , SCOTTI PAOLO , ORTENZI ANDREA , PREVIDE MASSARA ELISABETTA
Published: July 2010

The Early Jurassic dolomitized carbonates are a hydrocarbon exploration target in Northern Italy. Of these carbonates, the Liassic Albenza Formation platform and the overlying Sedrina Formation shelf were studied to define a pervasive dolomitization model and to shed light on dolomite distribution in the sub‐surface. Field work, as well as analyses of well cores, stable isotopes, trace elements and fluid inclusions, was carried out on the outcropping thrust belt and sub‐surface deformed foreland of the Southern Alps. Petrographic analyses showed a first, pervasive, replacement dolomitization phase (D1) followed by volumetrically less important dolomite cement precipitation phases (D2, D3 and D4). The δ18O values fall between −8·2‰ and 0·1‰ Vienna‐Pee Dee Belemnite with the more depleted samples belonging to dolomite cement‐rich dolostones; the δ13C ranges from 2·6‰ to 3·7‰ Vienna‐Pee Dee Belemnite. Analysis of trace elements showed different Fe and Mn contents in the sub‐surface and outcropping dolostones, and a higher Fe in the younger dolomite cements. An increase in the precipitation temperature (up to 130 °C from fluid inclusion data) and a decrease in diagenetic fluid salinity (from sea water to brackish) are observed from the first pervasive replacement dolomite to the dolomite cement phases. Field observations indicate that, in the Albenza Formation, dolomitization was limited to palaeohighs or faulted platform margins in the Early Jurassic carbonates. The pervasive replacement phase is interpreted based on a ‘compaction model’; the formation fluids expelled from compacting basinal carbonates could have funnelled along faults into permeable palaeohighs. The high homogenization temperature of the dolomite cements and decreased salinities indicate precipitation at great depth with an influx of meteoric water. These data, along with the thermal history, suggest that the dolomite cements precipitated according to the ‘tectonic squeegee’ dolomitization model. The dolomite precipitation temperature was set against the thermal history of the carbonate platform to interpret the timing of dolomite precipitation. The dolomite precipitation temperatures (90 to 100 °C) were reached in the studied formations first in the thrust fold belt (Early Tertiary, 60 Ma), and then in the foreland succession during the Late Tertiary (10 Ma). This observation suggests that the dolomite precipitation fronts moved southwards over time, recording a ‘diagenetic wave’ linked to the migration of the orogenic system. Observations suggest that the porosity increased during the first phase of replacement dolomitization while the dolomite cementation phases partially occluded the pores. The distribution of porous dolomitized bodies is therefore linked to the ‘compaction dolomitization’ model.
‘Virtual Parrots’ Confirm Mating Preferences of Female Budgerigars
Authors: Moravec Marin L. , Striedter Georg F. , Burley Nancy T.
Published: July 2010

Parrots comprise one of the several taxa in which life‐long learning of new vocal signals used in intraspecific communication is known to occur routinely. The functions and evolutionary bases of this ability are largely unknown. In the budgerigar (Melopsittacus undulatus), males typically imitate their partner’s contact call type during pair formation. However, a female’s initial choice among unfamiliar males is not based on their production of her call type, because birds without prior social contact rarely produce the same call type. Here, we demonstrate that female budgerigars prefer unfamiliar males with calls that are similar to their own, as measured by spectrogram cross‐correlation, but which are not imitations. This was shown by training females via operant conditioning to control access to movies of courting males and by systematically varying the audio tracks of these movies. Females learned this task easily and interacted with virtual males as if they were real. This methodology will be useful for exploring functions and mechanisms of social communication, because it eliminates the confounding impact of short‐term changes in a stimulus individual’s behavior on a test individual’s response. Our results suggest that the neuroplastic vocal abilities of budgerigars, and perhaps other parrots, have been shaped by sexual selection.
CALCIUM ANTAGONIST PROPERTY OF CPU228, A DOFETILIDE DERIVATIVE, CONTRIBUTES TO ITS LOW INCIDENCE OF TORSADES DE POINTES IN RABBITS
Authors: Huang Zhi‐Jiang , Dai De‐Zai , Li Na , Na Tao , Ji Min , Dai Yin
Published: July 2010

Torsades de pointes (TDP) is a severe adverse effect during the clinical use of dofetilide, a selective blocker of the rapid component of the delayed rectifier potassium channel (IKr). The present study was designed to test whether CPU228, a derivative of dofetilide with calcium (Ca2+) antagonist properties, could reduce TDP without reducing the blockade ofIKr.

The incidence of TDP in a rabbit model and the effective refractory period (ERP) were measured and compared for dofetilide and CPU228. Suppression ofIKrand the L‐type Ca2+current (ICa,L) and the Ca2+transients of isolated cardiomyocytes were investigated by whole‐cell patch‐clamp and Fluo‐3 dye spectrophotometry.

The incidence of TDP was greatly reduced by CPU228 relative to dofetilide, occurring in only one of six rabbits compared with five of six rabbits following dofetilide (P < 0.05). In isolated atria, prolongation of ERP by CPU228 was less than that of dofetilide and no reverse frequency dependence was observed. Negative inotropism by CPU228 was significant against positive inotropism by dofetilide. CPU228 inhibited bothIKrandICa,Lcurrents and the IC50forICa,Linhibition was 0.909 µmol/L. At 3 µmol/L, CPU228 significantly suppressed the Ca2+transients.

CPU228 is able to blockICa,L, contributing to decreased TDP, while also blockingIKractivity. By combined blockade ofIKrandICa,L, CPU228 shares the property of complex Class III anti‐arrhythmic agents.
Clustered protocadherin family
Authors: Yagi Takeshi
Published: July 2010

The brain is a complex system composed of enormous numbers of differentiated neurons, and brain structure and function differs among vertebrates. To examine the molecular mechanisms underlying brain structure and function, it is important to identify the molecules involved in generating neural diversity and organization. The clustered protocadherin (Pcdh) family is the largest subgroup of the diverse cadherin superfamily. The clustered Pcdh proteins are predominantly expressed in the brain and their gene structures in vertebrates are diversified. In mammals, the clustered Pcdh family consists of three gene clusters: Pcdh‐α, Pcdh‐β, and Pcdh‐γ. During brain development, this family is upregulated by neuronal differentiation, and Pcdh‐α is then dramatically downregulated by myelination. Clustered Pcdh expression continues in the olfactory bulb, hippocampus, and cerebellum until adulthood. Structural analysis of the first cadherin domain of the Pcdh‐α protein revealed it lacks the features that classical cadherins require for homophilic adhesiveness, but it contains Pcdh‐specific loop structures. In Pcdh‐α, an RGD motif on a specific loop structure binds β1‐integrin. For gene expression, the gene clusters are regulated by multiple promoters and alternative cis splicing. At the single‐cell level, several dozen Pcdh‐α and ‐γ mRNA are regulated monoallelically, resulting in the combinatorial expression of distinct variable exons. The Pcdh‐α and Pcdh‐γ proteins also form oligomers, further increasing the molecular diversity at the cell surface. Thus, the unique features of the clustered Pcdh family may provide the molecular basis for generating individual cellular diversity and the complex neural circuitry of the brain.
Manifold functions of the Nail‐Patella Syndrome gene Lmx1b in vertebrate development
Authors: Dai Jin‐Xia , Johnson Randy L. , Ding Yu‐Qiang
Published: July 2010

The LIM (Lin‐1, Isl‐1 and Mec‐3)‐homeodomain transcription factor 1 beta (Lmx1b) is widely expressed in vertebrate embryos, and is implicated in the development of diverse structures such as limbs, kidneys, eyes and brains. LMX1B mutations in humans cause an autosomal dominant inherited disease called nail‐patella syndrome (NPS), which is characterized by abnormalities of the arms and legs as well as kidney disease and glaucoma. Expression of Lmx1b in the dorsal compartment of growing limb buds is critical for specification of dorsal limb cell fates and consequently dorsoventral patterning of limbs. In addition, Lmx1b is involved in the differentiation of anterior eye structures, formation of the glomerular basement membrane in kidneys and development of the skeleton, especially calvarial bones. In the central nervous system, Lmx1b controls the inductive activity of isthmic organizer, differentiation and maintenance of central serotonergic neurons, as well as the differentiation and migration of spinal dorsal horn neurons. Although details of the genetic programs involved in these developmental events are largely unknown, it is suggested that Lmx1b plays central roles in fate determination or cell differentiation in these tissues. Sustained expression of Lmx1b in the postnatal and mature mouse brain suggests that it also plays important roles in brain maturation and in the regulation of normal brain functions. This review aims to highlight recent insights into the many activities of Lmx1b in vertebrates.
Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovary
Authors: Ha Choong‐Sik , Joo Bo‐Sun , Kim Seung‐Chul , Joo Jong‐Kil , Kim Hwi‐Gon , Lee Kyu‐Sup
Published: July 2010

Aims:  This study investigated whether estrogen administration during superovulation enhances oocyte quality using a mice model. We also investigated whether this estrogen treatment regulates the expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), in the ovary.

Method:  Female mice were co‐injected with various doses of estrogen (1 µM, 10 µM and 100 µM) and pregnant mare serum gonadotrophin during superovulation, followed by human chorionic gonadotrophin injection 48 hours later. Then they were mated with individual males. After 18 hours, zygotes were flushed and cultured to blastocyst. The expression of VEGF and eNOS in the ovary was examined using Western blot and immunohistochemistry. The control group was superovulated without estrogen.

Results:  Both numbers of ovulated zygotes and the rate of embryo development to blastocyst were significantly increased in the 1‐µM estrogen dose compared to the control group. VEGF and eNOS expressions were stimulated by estrogen treatment. In particular, VEGF expression was significantly increased at 1‐µM estrogen concentration, whereas, eNOS expression was significantly increased in all estrogen concentrations compared to controls.

Conclusions:  The study showed that estrogen co‐injection during superovulation increased the ovarian response, embryo developmental competence and expressions of VEGF and eNOS in the ovary.
Ovarian malignant melanoma without evidence of teratoma
Authors: Lee Seung‐Ho , Lee Kwang‐Beom , Shin Jin‐Woo , Chung Dong‐Hae , Park Chan‐Yong
Published: July 2010

A 46‐year‐old woman with ovarian malignant melanoma had advanced intraperitoneal metastasis, retroperitoneal and inguinal lymph node metastases. Extensive debulking surgery was performed and chemotherapy was given. Microscopically, no evidence of other accompanying tumor, such as teratoma was noted. Detailed examination of the patient failed to identify any evidence of another primary melanoma site. It is assumed that spontaneous regression of the primary lesion occurred. Despite the surgery and chemotherapy, the patient died within 2 months of diagnosis. Considering this case, it is assumed that the combination of surgical debulking and chemotherapy are not always beneficial in ovarian malignant melanoma and the prognosis of ovarian malignant melanoma is very poor.