bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best practice in smoking cessation services for pregnant women: results of a survey of three services reporting the highest national returns, and three beacon services
Authors: Lee Michelle , Hajek Peter , McRobbie Hayden , Owen Lesley 
Published: August 2006

Aims: The NHS allocated dedicated funds to establish specialist smoking cessation services for pregnant smokers in England in 2000. An early survey revealed some uncertainty as to how the new services should work and monitor their outcome. The current survey focused on identifying examples of good practice in this difficult new field. Method: Three services with the highest number of successful four-week quitters reported for the 2003/4 monitoring year were identified from Department of Health (DH) monitoring records, and three services were nominated from those known in the field as examples of best practice. There was no overlap between the two groups. All six services provided in-depth interviews. Results: All three highest ranking services that reported close to 100 per cent success rates included unaided quitters identified from hospital wards, rather then smokers actually treated. They had only minimal or average genuine treatment provision for pregnant smokers in place. The three beacon services far exceeded the national throughput and outcome average identified in the previous survey, and provided a wealth of useful information. Although they differed in staffing levels and other aspects of their activities, they all shared several key elements, including a systematic training of midwives in how to refer pregnant smokers, offering nicotine replacement treatment to almost all clients and having an efficient system of providing the prescriptions, offering flexible home visits, and providing intensive multi-session treatment delivered by a small number of dedicated staff. Conclusion: Smoking cessation services for pregnant women may need clearer guidance on what they are expected to provide, and how they should monitor their outcome. The key features of the beacon services can serve as a practical model of current best practice applicable across most PCTs.
The Future of Evidence in Evidence-based Practice
Authors: Magill Molly 
Published: August 2006

Summary: This article considers factors important to the broad-scale adoption of an evidence-based approach to social work practice (EBP). Elements of the EBP framework, and particularly directions for future research, are examined in terms of a number of criticisms voiced in the literature. Findings: Scholars in social work and allied disciplines have emphasized the implications of evidential hierarchies, and particularly the questionable clinical relevance of randomized controlled trials. While offering important considerations, arguments in opposition of EBP can be misconceived. Evidence-based practice is not merely a ‘best practice’ orientation, but a heuristic framework intended to foster explicit and accountable decisional capacities. Where EBP is limited highlights empirical questions that remain unanswered. Future directions for the approach will require the participation of both practitioners and researchers. Applications: The article delineates the role of operationalized clinical decision-making, local clinical research, and the unique utilities of evaluation methodologies in building knowledge for a more clinically relevant evidence-base for social work practice.
Parents, Professionals, and Paranoia
Authors: Piper Heather , Powell John , Smith Hannah 
Published: August 2006

Summary: In this paper, we appeal to professionals and others to take a more considered approach to the increasing panic relating to the touching of children of all ages. We attempt to disrupt the current trend by drawing attention to that which is currently being deferred in professional practice, yet which is evident in many formal and informal guidelines. We suggest that the contradictions we identify throughout the paper result more from a culture of fear than one of caring. We draw on our own small-scale earlier research experiences, and relevant and related literature in the area, but also note a scarcity of both in the UK context. We conclude that touching, at least in anglicized societies, has become an area that now requires fine judgements dependent on the interactive processes between all parties and that a broad-based analysis is clearly required. But we consider hesitation and ambiguity to be unavoidable in ethical decision making, something to be encouraged and not avoided by the search for blueprints, in our attempts to manage the perceived ‘risks’. Findings: Current practice is more dependent on fears of accusation and litigation than any concern for a child. Most child care workers ‘know’ this on the one hand, but nevertheless still attempt to justify their actions as sensible decision making. For example, a play group leader will claim he or she can’t put a plaster on a child because of a potential allergy: this is in spite of completed forms requesting information relating to allergies for each child, and allergies cease to be an issue anyway when a child is taken to the medical box and instructed from a distance on how to apply a plaster themselves. Contradictory accounts such as this are abundant in this area, and we suggest that many workers are behaving more like ‘victims’ than professionals. Applications: This paper is concerned with drawing attention to the need for all professionals working with children and young people of all ages to question their current and future decision making in relation to the wide range of touching practices that occur on a daily basis. Professionals should make their own mind up in relation to ethical matters, remembering that the ‘radicals’ of today become the ‘liberals’ of tomorrow.
T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage.
Authors: Talebian Laleh , Li Zhe , Guo Yalin , Gaudet Justin , Speck Maren E. , Sugiyama Daisuke , Kaur Prabhjot , Pear Warren S. , Maillard Ivan , Speck Nancy A. 
Published: August 2006

Abstract
The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4−CD8− double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.
Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors
Authors: Navas Tony A. , Mohindru Mani , Estes Myka , Ma Jing Ying , Sokol Lubomir , Pahanish Perry , Parmar Simrit , Haghnazari Edwin , Zhou Li , Collins Robert , Kerr Irene , Nguyen Aaron N. , Xu Yin , Platanias Leonidas C. , List Alan A. , Higgins Linda S. , Verma Amit 
Published: August 2006

AbstractThe myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38α by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38α isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS.
PKCδ regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation
Authors: Pula Giordano , Schuh Kai , Nakayama Keiko , Nakayama Keiichi I. , Walter Ulrich , Poole Alastair W. 
Published: August 2006

AbstractProtein kinase Cδ (PKCδ) has been shown by pharmacologic approaches to negatively regulate collagen-induced platelet aggregation. Here we addressed the molecular and cellular mechanisms underlying this negative regulation. Using PKCδ–/– platelets, we show that the mechanism did not involve altered inside-out signaling to integrin αIIbβ3 and did not affect early signaling events downstream of GPVI, because there was no difference in tyrosine phosphorylation of PLCγ2 between wild-type and PKCδ–/– platelets. There was also no increase in secretion of dense granule content, in contrast to studies using rottlerin where secretion was enhanced. Importantly, however, there was marked enhancement of filopodia generation in PKCδ–/– platelets upon adhesion to collagen compared with wild-type platelets. Filopodia play an essential role regulating adhesive events leading to platelet aggregation by increasing platelet-platelet contact. We show that the critical effector for PKCδ is vasodilator-stimulated phosphoprotein (VASP), a major regulator of actin cytoskeleton dynamics. PKCδ physically interacts with VASP constitutively and regulates its phosphorylation on Ser157. In VASP–/– platelets, the enhancement of filopodia generation, actin polymerization, and platelet aggregation by rottlerin is ablated. PKCδ is therefore a critical negative regulator of filopodia, and hence platelet aggregation, through a functional interaction with the actin organizer VASP.
Recording long-term potentiation of synaptic transmission by three-dimensional multi-electrode arrays
Authors: Kopanitsa Maksym V , Afinowi Nurudeen O , Grant Seth GN 
Published: August 2006

AbstractBackgroundMulti-electrode arrays (MEAs) have become popular tools for recording spontaneous and evoked electrical activity of excitable tissues. The majority of previous studies of synaptic transmission in brain slices employed MEAs with planar electrodes that had limited ability to detect signals coming from deeper, healthier layers of the slice. To overcome this limitation, we used three-dimensional (3D) MEAs with tip-shaped electrodes to probe plasticity of field excitatory synaptic potentials (fEPSPs) in the CA1 area of hippocampal slices of 129S5/SvEvBrd and C57BL/6J-TyrC-Brdmice.ResultsUsing 3D MEAs, we were able to record larger fEPSPs compared to signals measured by planar MEAs. Several stimulation protocols were used to induce long-term potentiation (LTP) of synaptic responses in the CA1 area recorded following excitation of Schäffer collateral/commissural fibres. Either two trains of high frequency tetanic stimulation or three trains of theta-burst stimulation caused a persistent, pathway specific enhancement of fEPSPs that remained significantly elevated for at least 60 min. A third LTP induction protocol that comprised 150 pulses delivered at 5 Hz, evoked moderate LTP if excitation strength was increased to 1.5× of the baseline stimulus. In all cases, we observed a clear spatial plasticity gradient with maximum LTP levels detected in proximal apical dendrites of pyramidal neurones. No significant differences in the manifestation of LTP were observed between 129S5/SvEvBrd and C57BL/6J-TyrC-Brdmice with the three protocols used. All forms of plasticity were sensitive to inhibition ofN-methyl-D-aspartate (NMDA) receptors.ConclusionPrincipal features of LTP (magnitude, pathway specificity, NMDA receptor dependence) recorded in the hippocampal slices using MEAs were very similar to those seen in conventional glass electrode experiments. Advantages of using MEAs are the ability to record from different regions of the slice and the ease of conducting several experiments on a multiplexed platform which could be useful for efficient screening of novel transgenic mice.
Adiponectin-induced secretion of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) is impaired in monocytes from patients with type I diabetes
Authors: Abke Sabine , Neumeier Markus , Weigert Johanna , Wehrwein Gabriele , Eggenhofer Elke , Schäffler Andreas , Maier Kevin , Aslanidis Charalampos , Schölmerich Jürgen , Buechler Christa 
Published: August 2006

Abstract

Background
Systemic adiponectin is reduced in patients with cardiovascular disease (CVD) and low adiponectin may contribute to the pathogenesis of atherosclerosis. However, circulating adiponectin is elevated in type 1 diabetes (T1D) patients, who have also a higher incidence to develop CVD. Because monocytes play an important role in atherosclerosis, we analysed the influence of adiponectin on cytokine and chemokine release in monocytes from T1D patients and controls.

Methods
Systemic adiponectin was determined in the plasma and the high-molecular weight (HMW) form of adiponectin was analysed by immunoblot. Monocytes were isolated from T1D patients and controls and the adiponectin-stimulated release of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) was analysed.

Results
Systemic adiponectin was higher in T1D patients. Immunoblot analysis of the plasma indicate abundance of HMW adiponectin in T1D patients and controls. IL-6, CCL2 and CXCL8 secretion in response to adiponectin were found induced in monocytes from controls whereas only IL-6 was upregulated in T1D cells. The induction of IL-6 by adiponectin was abrogated by an inhibitor of the NFκB pathway.

Conclusion
These data indicate that adiponectin-mediated induction of IL-6, CCL2 and CXCL8 is disturbed in monocytes from T1D patients and therefore elevated systemic adiponectin in T1D patients may be less protective when compared to controls.
Endotoxin-induced myocardial dysfunction in senescent rats
Authors: Rozenberg Sandrine , Besse Sophie , Brisson Hélène , Jozefowicz Elsa , Kandoussi Abdelmejid , Mebazaa Alexandre , Riou Bruno , Vallet Benoît , Tavernier Benoît 
Published: August 2006

Abstract
Introduction
Aging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction.

Methods
Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca2+ sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO2) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated.

Results
LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 ± 4 vs 53 ± 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 ± 7 vs 100 ± 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca2+ sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO2 were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals.

Conclusion
Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca2+-sensitizing agents may not be as effective in aged subjects as in younger subjects.
Regulation of Akt/PKB by phosphatidylinositol 3-kinase-dependent and -independent pathways in B-cell chronic lymphocytic leukemia cells: role of protein kinase Cβ
Authors: Barragán Montserrat , de Frias Mercè , Iglesias-Serret Daniel , Campàs Clara , Castaño Esther , Santidrián Antonio F , Coll-Mulet Llorenç , Cosialls Ana M , Domingo Alicia , Pons Gabriel , Gil Joan 
Published: August 2006

Abstract
Apoptosis of B cell chronic lymphocytic leukemia (B-CLL) cells is regulated by the PI-3K-Akt pathway. In the present work, we have analyzed the mechanisms of Akt phosphorylation in B-CLL cells. Freshly isolated cells present basal Akt phosphorylation, which is PI-3K-dependent, as incubation with the PI-3K inhibitor LY294002 decreased Ser-473 and Thr-308 phosphorylation in most samples analyzed (seven out of 10). In three out of 10 cases, inhibition of protein kinase C (PKC) inhibited basal Akt phosphorylation. Stromal cell-derived factor-1α, IL-4, and B cell receptor activation induced PI-3K-dependent Akt phosphorylation. PMA induced the phosphorylation of Akt at Ser-473 and Thr-308 and the phosphorylation of Akt substrates, independently of PI-3K in B-CLL cells. In contrast, PKC-mediated phosphorylation of Akt was PI-3K-dependent in normal B cells. Finally, a specific inhibitor of PKCβ blocked the phosphorylation and activation of Akt by PMA in B-CLL cells. Taken together, these results suggest a model in which Akt could be activated by two different pathways (PI-3K and PKCβ) in B-CLL cells.
Pivotal Advances: High-mobility group box 1 protein—a cytokine with a role in cardiac repair
Authors: Germani Antonia , Limana Federica , Capogrossi Maurizio C 
Published: August 2006

AbstractThe nuclear protein high-mobility group box 1 (HMGB1) has been largely characterized for its role in inflammation. However, HMGB1 released by inflammatory cells, as well as by necrotic cells, may also act as a signal of tissue damage and participate in tissue repair by recruiting stem cells to the injury site. The emergence of this function has focused the interest on HMGB1 as a molecule with an active role in tissue regeneration. We recently demonstrated that HMGB1 administration in a mouse model of myocardial infarction activates cardiac stem cells and promotes their differentiation into cardiomyocytes. The regenerative effect results in the improvemet of cardiac function. In this review, we highlight the beneficial role of HMGB1 and discuss growth factor-based therapeutic approaches for the treatment of myocardial infarction.
Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis
Authors: Lorenowicz Magdalena J , van Gils Janine , de Boer Martin , Hordijk Peter L , Fernandez-Borja Mar 
Published: August 2006

Abstract
Extravasation of leukocytes is a crucial process in the immunological defense. In response to a local concentration of chemokines, circulating leukocytes adhere to and migrate across the vascular endothelium toward the inflamed tissue. The small guanosinetriphosphatase Rap1 plays an important role in the regulation of leukocyte adhesion, polarization, and chemotaxis. We investigated the role of a guanine nucleotide exchange protein for Rap1 directly activated by cAMP (Epac1) in adhesion and chemotaxis in a promonocytic cell line and in primary monocytes. We found that Epac1 is expressed in primary leukocytes, platelets, CD34-positive hematopoietic cells, and the leukemic cell lines U937 and HL60. Epac activation with an Epac-specific cAMP analog induced Rap1 activation, β1-integrin-dependent cell adhesion, and cell polarization. In addition, activated Epac1 enhanced chemotaxis of U937 cells and primary monocytes. Similar to activation of Epac1, stimulation of cells with serotonin to induce cAMP production resulted in Rap1 activation, increased cell adhesion and polarization, and enhanced chemotaxis. The effects of serotonin on U937 cell adhesion were dependent on cAMP production but could not be blocked by a protein kinase A inhibitor, implicating Epac in the regulation of serotonin-induced adhesion. In summary, our work reveals the existence of previously unrecognized cAMP-dependent signaling in leukocytes regulating cell adhesion and chemotaxis through the activation of Epac1.
Roles of leukocytosis and cysteinyl leukotriene in polymorphonuclear leukocyte-dependent plasma extravasation
Authors: Tokita Kazutaka , Uchida Yasuhiro , Yamamoto Tetsuro 
Published: August 2006

AbstractThe PMN-dependent plasma extravasation is a major mechanism of permeability enhancement in acute inflammation. To reveal the pathophysiological significance of the PMN-dependent plasma extravasation, we prepared a systemic leukocytotic guinea pig model by a daily injection of recombinant human (rh)G-CSF. The extent of the PMN-dependent plasma extravasation, regarded as the late-phase permeability induced by an intradermal injection of zymosan-activated guinea pig plasma (ZAP) or of rhC5a, clearly correlated to the circulating PMN number. The augmentation of local response following the systemic response seemed to be the characteristic feature of the PMN-dependent plasma extravasation. We then revealed the molecular mechanism of the PMN-dependent plasma extravasation. Neither the antihistaminic agent diphenhydramine, nor the bradykinin B2 receptor antagonist, HOE140, affected the ZAP-induced, late-phase extravasation. In contrast to this, pretreatment with an antagonist of cysteinyl leukotriene (cys-LT) 1 receptor, pranlukast, significantly reduced the late-phase extravasation. Similarly, it was reduced by pretreatment with a 5-lipoxygenase inhibitor, MK-886, indicating the participation of cys-LTs in the PMN-dependent plasma extravasation. Histologically, pretreatment with pranlukast or MK-886 did not affect the ZAP-induced PMN infiltration. Consistently, a combined treatment with pranlukast and diphenhydramine completely suppressed the early-phase extravasation. As pranlukast pretreatment did not affect plasma extravasation induced by mast cell degranulation, and depletion of platelets did not influence the pranlukast-inhibitable plasma extravasation induced by rhC5a injection, cys-LTs are most likely produced by transcellular biosynthesis involving PMNs and vascular wall cells.