bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing the delivery of safeguarding services: A role for volunteers?
Authors: Tunstill Jane , Malin Nigel 
Published: March 2011

• Summary: This article reports findings from an evaluation of the Volunteers in Child Protection (ViCP) pilot study commissioned by Community Service Volunteers (CSV) and conducted in two English authorities. The study examined expectations, experiences and identified benefits for three stakeholder groups – families, volunteers and social workers; and offered an opportunity to explore the implications of developing an expanded role for volunteers, within child protection services. The study sample comprised the first 14 families in the two authorities to be matched with a volunteer, and including the respective social workers and volunteers, in all 21 individuals were interviewed at two points in time. • Findings: Conclusions to be drawn are that the ViCP project was successful at recruiting and mentoring volunteers to work with families with complex needs; and their contributions suggest that local authority social work could draw on such initiatives to provide support functions. Its inputs could mitigate the negative effects of frequency of change of social workers, and help reduce the increasing dominance of a narrow model of child protection. • Applications: 1) There is an inevitable inter-dependent relationship between the culture of local authority children’s services departments, including the point at, and frequency with which, social workers can access supplementary family support services, from a voluntary sector agency such as ViCP. 2) A ‘shared ownership’ model of social work ( Laming, 2009 ) is explored whereby mentored volunteers help to broaden and enlarge the evidence-base on families to enable improved decision-making and risk assessment.
A high ankle-brachial index is associated with increased aortic pulse wave velocity: the Czech post-MONICA study
Authors: Wohlfahrt Peter , Palouš Daniel , Ingrischová Michaela , Krajčoviechová Alena , Seidlerová Jitka , Galovcová Markéta , Bruthans Jan , Jozífová Marie , Adámková Věra , Filipovský Jan , Cífková Renata 
Published: March 2011

Background: Ankle brachial index (ABI) has been increasingly used in general practice to identify individuals with low ABI at high cardiovascular risk. However, there has been no consensus on the clinical significance of high ABI. The aim of our study was to compare aortic stiffness as a marker of cardiovascular risk in individuals with low (<1.0), normal (1.0–1.4), and high ABI (>1.4).Methods: A total of 911 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, aged 54 ± 13.5 years, 47% of men) were examined. ABI was measured using a handheld Doppler and aortic pulse wave velocity (aPWV) using the Sphygmocor device.Results: Of the 911 individuals, 28 (3.1%) had low ABI and 23 (2.5%) high ABI. There was a U-shaped association between aPWV and ABI. aPWV was significantly higher in individuals with low and high ABI compared with the normal ABI group (11.1 ± 2.8, 8.3 ± 2.3, p < 0.001; 10.8 ± 2.5, 8.3 ± 2.3 m/s, p < 0.001, respectively). In a model adjusted for age, sex, systolic, diastolic, mean blood pressure and examiner, aPWV remained increased in both extreme ABI groups compared with the normal ABI group. In logistic regression analysis, aPWV together with glucose level, male sex, and a history of deep venous thrombosis were independent predictors of high ABI, while cholesterol was not.Conclusion: This is the first study showing increased aortic stiffness in individuals with high ABI, presumably responsible for increased left ventricular mass described previously in this group. These findings suggest increased cardiovascular risk of high ABI individuals.
Engaged scholarship and research impact: integrating the doing and using of research in practice
Authors: McCormack Brendan 
Published: March 2011

Demonstrating impact from research has always been a key consideration in the knowledge production business. However, it can be argued that the models and frameworks available for enabling such impact to be demonstrated are poorly developed. Those that do exist are predominantly derived from a linear uni-dimensional perspective of the knowledge flow from the academy to practice. Little sustained attention has been given to the development of models and ways of working that go beyond traditional approaches to impact monitoring through impact factors and citation indices. Engaged scholarship offers a framework that has as an explicit intention, the creation of connections between researchers/universities and practitioners/health care providers. In this paper a model is offered derived from the theory of ‘engaged scholarship’. The principles of engaged scholarship will be outlined, as well as an articulation of engaged scholarship as an approach to the co-production of knowledge. An example of a practice development and evaluation study will be offered that is consistent with the principles of engaged scholarship. The need for a strategic approach to the development of engaged scholarship will be highlighted, as well as the need for sustained partnerships between the academy and practice.
Down-regulation of stathmin expression is required for megakaryocyte maturation and platelet production
Authors: Iancu-Rubin Camelia , Gajzer David , Tripodi Joseph , Najfeld Vesna , Gordon Ronald E. , Hoffman Ronald , Atweh George F. 
Published: March 2011

AbstractThe final stages of of megakaryocyte (MK) maturation involve a series of steps, including polyploidization and proplatelet formation. Although these processes are highly dependent on dynamic changes in the microtubule (MT) cytoskeleton, the mechanisms responsible for regulation of MTs in MKs remain poorly defined. Stathmin is a highly conserved MT-regulatory protein that has been suggested to play a role in MK differentiation of human leukemic cell lines. However, previous studies defining this relationship have reached contradictory conclusions. In this study, we addressed this controversy and investigated the role of stathmin in primary human MKs. To explore the importance of stathmin down-regulation during megakaryocytopoiesis, we used a lentiviral-mediated gene delivery system to prevent physiologic down-regulation of stathmin in primary MKs. We demonstrated that sustained expression of constitutively active stathmin delayed cytoplasmic maturation (ie, glycoprotein GPIb and platelet factor 4 expression) and reduced the ability of MKs to achieve high levels of ploidy. Moreover, platelet production was impaired in MKs in which down-regulation of stathmin expression was prevented. These studies indicate that suppression of stathmin is biologically important for MK maturation and platelet production and support the importance of MT regulation during the final stages of thrombopoiesis.
Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts
Authors: Renella Raffaele , Roberts Nigel A. , Brown Jill M. , De Gobbi Marco , Bird Louise E. , Hassanali Tasneem , Sharpe Jacqueline A. , Sloane-Stanley Jacqueline , Ferguson David J. P. , Cordell Jacqueline , Buckle Veronica J. , Higgs Douglas R. , Wood William G. 
Published: March 2011

AbstractCongenital dyserythropoietic anemia type 1 (CDA-1), a rare inborn anemia characterized by abnormal chromatin ultrastructure in erythroblasts, is caused by abnormalities in codanin-1, a highly conserved protein of unknown function. We have produced 3 monoclonal antibodies to codanin-1 that demonstrate its distribution in both nucleus and cytoplasm by immunofluorescence and allow quantitative measurements of patient and normal material by Western blot. A detailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genome-wide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1α in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1α is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1α antibodies. Furthermore, we show colocalization of codanin-1 with Sec23B, the protein defective in CDA-2 suggesting that the CDAs might be linked at the molecular level. Mice containing a gene-trapped Cdan1 locus demonstrate its widespread expression during development. Cdan1gt/gt homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis.
An important role of lymphatic vessel activation in limiting acute inflammation
Authors: Huggenberger Reto , Siddiqui Shoib S. , Brander Daniela , Ullmann Stefan , Zimmermann Kathrin , Antsiferova Maria , Werner Sabine , Alitalo Kari , Detmar Michael 
Published: March 2011

AbstractIn contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic vessels. Transgenic delivery of the lymphangiogenic factors VEGF-C and the VEGFR-3 specific ligand mouse VEGF-D significantly limited acute skin inflammation in both experimental models, with a strong reduction of dermal edema. Expression of VEGFR-3 by lymphatic endothelium was strongly down-regulated at the mRNA and protein level in acutely inflamed skin, and no VEGFR-3 expression was detectable on inflamed blood vessels and dermal macrophages. There was no major change of the inflammatory cell infiltrate or the composition of the inflammatory cytokine milieu in the inflamed skin of VEGF-C or VEGF-D transgenic mice. However, the increased network of lymphatic vessels in these mice significantly enhanced lymphatic drainage from the ear skin. These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation.
MicroRNAs in platelet production and activation
Authors: Edelstein Leonard C. , Bray Paul F. 
Published: March 2011

AbstractMicroRNAs are small RNA molecules that modulate protein expression by degrading mRNA or repressing translation. They have been shown to play important roles in hematopoiesis, including embryonic stem cell differentiation, erythropoiesis, granulocytopoiesis/monocytopoiesis, lymphopoiesis, and megakaryocytopoiesis. miR-150 and miR-155 play divergent roles in megakaryocytopoiesis, with the former promoting development of megakaryocytes at the expense of erythrocytes and the latter causing a reduction in megakaryocyte colony formation. Platelets also contain fully functional miRNA machinery, and certain miRNA levels in platelets have been found to coordinate with reactivity to specific agonists and to pathologic states. This review will cover the current state of knowledge of miRNAs in megakaryocytes and platelets and the exciting possibilities for future research.
Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review
Authors: De Luca D. , Cogo P. , Zecca E. , Piastra M. , Pietrini D. , Tridente A. , Conti G. , Carnielli V.P. 
Published: March 2011

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants.This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs.We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.
Pulmonary arterial hypertension: a comparison between children and adults
Authors: Barst R.J. , Ertel S.I. , Beghetti M. , Ivy D.D. 
Published: March 2011

The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults.The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension.Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children.Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines.In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).
Autoimmunity-related demyelination in infection by Japanese encephalitis virus
Authors: Tseng Yu-Fen , Wang Chien-Chih , Liao Shuen-Kuei , Chuang Ching-Kai , Chen Wei-June 
Published: March 2011

Abstract
Japanese encephalitis (JE) virus is the most common cause of epidemic viral encephalitis in the world. The virus mainly infects neuronal cells and causes an inflammatory response after invasion of the parenchyma of the brain. The death of neurons is frequently observed, in which demyelinated axons are commonly seen. The mechanism that accounts for the occurrence of demyelination is ambiguous thus far. With a mouse model, the present study showed that myelin-specific antibodies appeared in sera, particularly in those mice with evident symptoms. Meanwhile, specific T cells proliferating in response to stimulation by myelin basic protein (MBP) was also shown in these mice. Taken together, our results suggest that autoimmunity may play an important role in the destruction of components, e.g., MBP, of axon-surrounding myelin, resulting in demyelination in the mouse brain after infection with the JE virus.
Inhibition of granulocyte migration by tiotropium bromide
Authors: Vacca Gabriela , Randerath Winfried J , Gillissen Adrian 
Published: March 2011

AbstractStudy objectivesNeutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD). Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways. On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).MethodAM and neutrophils were collected from 71 COPD patients. Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 μg/ml). AM supernatant was tested for TNFα, IL8, IL6, LTB4, GM-CSF, MIPα/β and ROS. It was further used in a 96-well chemotaxis chamber to stimulate the migration of fluorescence labelled neutrophils. Control stimulants consisted of acetylcholine (ACh), carbachol, muscarine or oxotremorine and in part PMA (phorbol myristate acetate, 0.1 μg/ml). Potential contribution of M1-3-receptors was ascertained by a) analysis of mRNA transcription by RT-PCR, and b) co-incubation with selective M-receptor inhibitors.ResultsSupernatant from AM stimulated with LPS induced neutrophilic migration which could be reduced by tiotropium in a dose dependent manner: 22.1 ± 10.2 (3 nM), 26.5 ± 18,4 (30 nM), and 37.8 ± 24.0 (300 nM, p < 0.001 compared to non-LPS activated AM). Concomitantly TNFα release of stimulated AM dropped by 19.2 ± 7.2% of control (p = 0.001). Tiotropium bromide did not affect cellular IL8, IL6, LTB4, GM-CSF and MIPα/β release in this setting. Tiotropium (30 nM) reduced ROS release of LPS stimulated AM by 36.1 ± 15.2% (p = 0.002) and in carbachol stimulated AM by 46.2 ± 30.2 (p < 0.001). M3R gene expression dominated over M2R and M1R. Chemotaxis inhibitory effect of tiotropium bromide was mainly driven by M3R inhibition.ConclusionOur data confirm that inhibiting muscarinic cholinergic receptors with tiotropium bromide reduces TNFα mediated chemotactic properties and ROS release of human AM, and thus may contribute to lessen cellular inflammation.
An expression profile analysis of ES cell-derived definitive endodermal cells and Pdx1-expressing cells
Authors: Ogaki Soichiro , Harada Seiko , Shiraki Nobuaki , Kume Kazuhiko , Kume Shoen 
Published: March 2011

Abstract

Background
We developed an efficient in vitro method to differentiate mouse ES cells into the definitive endoderm (DE) and then Pdx1-expressing pancreatic lineages using mesodermal-derived supporting cells, M15. Using this method, resulting ES cell-derived DE and Pdx1-expressing cells were isolated by cell sorting, and their gene expression profiles were investigated with DNA microarray. Genes that were specifically expressed in DE and/or in Pdx1-expressing cells were extracted and their expression patterns in normal embryonic development were studied.

Results
Genes whose expression increased in DE and Pdx1 positive cells compared to the undifferentiated ES cells were chosen and in situ hybridizations were performed. Out of 54 genes examined, 27 were expressed in the DE of E8.5 mouse embryos and 15 genes were expressed in distinct domains in the pancreatic buds of E14.5 embryos. Among those genes expressed were Foxq1, CpM, Foxp4, Pcdh1, and Zmiz1, which were previously reported in other endodermal tissues. Genes, such as Parm1, Tmem184a, Hipk2 and Sox4 were reported to be expressed during early pancreatic development. Nptx2, C2cd4b, Tcf7l2 and Kiss1r were reported to be associated with beta cell or pancreatic functions in the adult. Akr1c19, Aebp2, Pbxip1 and Creb3l1, were novel and have not been described as being expressed either in DE or the pancreas.

Conclusions
We identified 27 genes, including 4 novel genes expressed in DE and pancreatic progenitor cells during normal development using an ES cell in vitro differentiation system. These results showed that DE cells and Pdx1/GFP-expressing cells obtained from our M15 based differentiation method mimic cells during the normal developmental processes. Additionally, ES cells are an excellent model for studies of early developmental processes.
Coordinated gene expression during gilthead sea bream skeletogenesis and its disruption by nutritional hypervitaminosis A
Authors: Fernández Ignacio , Darias Maria , Andree Karl B , Mazurais David , Zambonino-Infante Jose Luís , Gisbert Enric 
Published: March 2011

Abstract
Background
Vitamin A (VA) has a key role in vertebrate morphogenesis, determining body patterning and growth through the control of cell proliferation and differentiation processes. VA regulates primary molecular pathways of those processes by the binding of its active metabolite (retinoic acid) to two types of specific nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which promote transcription of downstream target genes. This process is well known in most of higher vertebrates; however, scarce information is available regarding fishes. Therefore, in order to gain further knowledge of fish larval development and its disruption by nutritional VA imbalance, the relative expression of some RARs and RXRs, as well as several genes involved in morpho- and skeletogenesis such as peroxisome proliferator-activated receptors (PPARA, PPARB and PPARG); retinol-binding protein (RBP); insulin-like growth factors I and II (IGF1 and IGF2, respectively); bone morphogenetic protein 2 (Bmp2); transforming growth factor β-1 (TGFB1); and genes encoding different extracellular matrix (ECM) proteins such as matrix Gla protein (mgp), osteocalcin (bglap), osteopontin (SPP1), secreted protein acidic and rich in cysteine (SPARC) and type I collagen α1 chain (COL1A1) have been studied in gilthead sea bream.

Results
During gilthead sea bream larval development, specific expression profiles for each gene were tightly regulated during fish morphogenesis and correlated with specific morphogenetic events and tissue development. Dietary hypervitaminosis A during early larval development disrupted the normal gene expression profile for genes involved in RA signalling (RARA), VA homeostasis (RBP) and several genes encoding ECM proteins that are linked to skeletogenesis, such as bglap and mgp.

Conclusions
Present data reflects the specific gene expression patterns of several genes involved in larval fish RA signalling and skeletogenesis; and how specific gene disruption induced by a nutritional VA imbalance underlie the skeletal deformities. Our results are of basic interest for fish VA signalling and point out some of the potential molecular players involved in fish skeletogenesis. Increased incidences of skeletal deformities in gilthead sea bream fed with hypervitaminosis A were the likely ultimate consequence of specific gene expression disruption at critical development stages.
Recent evolution of the NF-κB and inflammasome regulating protein POP2 in primates
Authors: Atianand Maninjay K , Fuchs Travis , Harton Jonathan A 
Published: March 2011

Abstract

Background
Pyrin-only protein 2 (POP2) is a small human protein comprised solely of a pyrin domain that inhibits NF-κB p65/RelA and blocks the formation of functional IL-1β processing inflammasomes. Pyrin proteins are abundant in mammals and several, like POP2, have been linked to activation or regulation of inflammatory processes. Because POP2 knockout mice would help probe the biological role of inflammatory regulation, we thus considered whether POP2 is common in the mammalian lineage.

Results
BLAST searches revealed that POP2 is absent from the available genomes of not only mice and rats, but those of other domestic mammals and New World monkeys as well. POP2 is however present in the genome of the primate species most closely related to humans including Pan troglodytes (chimpanzees), Macaca mulatta (rhesus macaques) and others. Interestingly, chimpanzee POP2 is identical to human POP2 (huPOP2) at both the DNA and protein level. Macaque POP2 (mqPOP2), although highly conserved is not identical to the human sequence; however, both functions of the human protein are retained. Further, POP2 appears to have arisen in the mammalian genome relatively recently (~25 mya) and likely derived from retrogene insertion of NLRP2.

Conclusion
Our findings support the hypothesis that the NLR loci of mammals, encoding proteins involved in innate and adaptive immunity as well as mammalian development, have been subject to recent and strong selective pressures. Since POP2 is capable of regulating signaling events and processes linked to innate immunity and inflammation, its presence in the genomes of hominids and Old World primates further suggests that additional regulation of these signals is important in these species.