bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKα kinases
Authors: Lefort Karine , Mandinova Anna , Ostano Paola , Kolev Vihren , Calpini Valerie , Kolfschoten Ingrid , Devgan Vikram , Lieb Jocelyn , Raffoul Wassim , Hohl Daniel , Neel Victor , Garlick Jonathan , Chiorino Giovanna , Dotto G. Paolo
Published: March 2007

Little is known about the regulation and function of the Notch1 gene in negative control of human tumors. Here we show that Notch1 gene expression and activity are substantially down-modulated in keratinocyte cancer cell lines and tumors, with expression of this gene being under p53 control in these cells. Genetic suppression of Notch signaling in primary human keratinocytes is sufficient, together with activated ras, to cause aggressive squamous cell carcinoma formation. Similar tumor-promoting effects are also caused by in vivo treatment of mice, grafted with keratinocytes expressing oncogenic ras alone, with a pharmacological inhibitor of endogenous Notch signaling. These effects are linked with a lesser commitment of keratinocytes to differentiation, an expansion of stem cell populations, and a mechanism involving up-regulation of ROCK1/2 and MRCKα kinases, two key effectors of small Rho GTPases previously implicated in neoplastic progression. Thus, the Notch1 gene is a p53 target with a role in human tumor suppression through negative regulation of Rho effectors.
Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast
Authors: Ito-Harashima Sayoko , Kuroha Kazushige , Tatematsu Tsuyako , Inada Toshifumi
Published: March 2007

mRNA surveillance system represses the expression of nonstop mRNA by rapid mRNA degradation and translation repression. Here we show that the level of protein product of nonstop mRNA containing a poly(A) tail was reduced 100-fold, and this reduction was due to rapid mRNA degradation, translation repression, and protein destabilization, at least in part, by the proteasome. Insertion of a poly(A) tract upstream of a termination codon resulted in translation repression and protein destabilization, but not rapid mRNA decay. We propose that translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization.
Microtubule-induced cortical cell polarity
Authors: Siegrist Sarah E. , Doe Chris Q.
Published: March 2007

Most cells are polarized. Embryonic and stem cells can use their polarity to generate cell diversity by asymmetric cell division, whereas differentiated cells use their polarity to execute specific functions. For example, fibroblasts form an actin-rich leading edge required for cell migration, neurons form distinctive axonal and dendritic compartments important for directional signaling, and epithelial cells have apical and basolateral cortical domains necessary for maintaining tissue impermeability. It is well established that actin and actin-associated proteins are essential for generating molecular and morphological cell polarity, but only recently has it become accepted that microtubules can induce and/or maintain polarity. One common feature among different cell types is that microtubules can establish the position of cortical polarity, but are not required for cortical polarity per se. In this review, we discuss how different cell types utilize microtubules and microtubule-associated signaling pathways to generate cortical cell polarity, highlight common mechanisms, and discuss open questions for directing future research.
Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly
Authors: Vogel Rutger O. , Janssen Rolf J.R.J. , van den Brand Mariël A.M. , Dieteren Cindy E.J. , Verkaart Sjoerd , Koopman Werner J.H. , Willems Peter H.G.M. , Pluk Wendy , van den Heuvel Lambert P.W.J. , Smeitink Jan A.M. , Nijtmans Leo G.J.
Published: March 2007

Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathways) in the assembly of mitochondrial complex I (NADH:ubiquinone oxidoreductase). An N-terminal targeting signal directs Ecsit to mitochondria, where it interacts with assembly chaperone NDUFAF1 in 500- to 850-kDa complexes as demonstrated by affinity purification and vice versa RNA interference (RNAi) knockdowns. In addition, Ecsit knockdown results in severely impaired complex I assembly and disturbed mitochondrial function. These findings support a function for Ecsit in the assembly or stability of mitochondrial complex I, possibly linking assembly of oxidative phosphorylation complexes to inflammatory response and embryonic development.
The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
Authors: Bracken Adrian P. , Kleine-Kohlbrecher Daniela , Dietrich Nikolaj , Pasini Diego , Gargiulo Gaetano , Beekman Chantal , Theilgaard-Mönch Kim , Minucci Saverio , Porse Bo T. , Marine Jean-Christophe , Hansen Klaus H. , Helin Kristian
Published: March 2007

The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood. Here, we show that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 is down-regulated in stressed and senescing populations of cells, coinciding with decreased levels of associated H3K27me3, displacement of BMI1, and activation of transcription. These results provide a model for how the INK4A-ARF locus is activated and how Polycombs contribute to cancer.
Trends in the utilization and wastage of coagulation factor concentrates: the application of a regional tracking programme
Authors: ARNOLD D. M. , WEBERT K. E. , CARRUTHERS J. , ALMONTE T. , DECKER K. , SEROSKI W. , REED J. , CHAN A. K. C. , PAI M. , WALKER I.
Published: March 2007

Summary.  The Commission of Inquiry on the Blood System in Canada (‘Krever Commission’, 1997) recommended an active programme of surveillance for all blood products. To describe trends in the utilization of coagulation factor concentrates using a comprehensive factor tracking programme. Between 2001 and 2004 in the region of Southern Ontario, we prospectively tracked all coagulation factor concentrates that were distributed from the national blood supplier, issued by hospitals for inpatient use or for home infusions, infused at hospital facilities or at home and wasted. Discrepancies were reconciled by independent audits. Trends in the utilization of FVIII, FIX and FVIIa concentrates are reported. A total of 466 patients with inherited or acquired bleeding disorders were registered. Utilization of FVIII, FIX and FVIIa increased by an average of 13.7%, 33.2% and 34.2% per year respectively. Most FVIII and FIX infusions were administered at home while most FVIIa infusions were in hospital. The increase in FVIII and FIX usage was attributable to an increase in per‐patient use, predominantly for prophylaxis. In total, 1.7% of coagulation factor concentrates was wasted during the study period, at a cost of over 1 million Canadian dollars. Utilization of coagulation factor concentrates increased steadily during the study period. A regional programme to track utilization is feasible and may be used to describe trends, assist planning, and reduce costs by minimizing wastage.
Interleukin‐12‐ and interferon‐γ‐mediated natural killer cell activation by Agaricus blazei Murill
Authors: Yuminamochi Eri , Koike Taisuke , Takeda Kazuyoshi , Horiuchi Isao , Okumura Ko
Published: March 2007

Dried fruiting bodies of Agaricus blazei Murill (A. blazei) and its extracts have generally used as complementary and alternative medicines (CAMs). Here, we report that the oral administration of A. blazei augmented cytotoxicity of natural killer (NK) cells in wild‐type (WT) C57BL/6, C3H/HeJ, and BALB/c mice. Augmented cytotoxicity was demonstrated by purified NK cells from treated wild‐type (WT) and RAG‐2‐deficient mice, but not from interferon‐γ (IFN‐γ) deficient mice. NK cell activation and IFN‐γ production was also observed in vitro when dendritic cell (DC)‐rich splenocytes of WT mice were coincubation with an extract of A. blazei. Both parameters were largely inhibited by neutralizing anti‐interleukin‐12 (IL‐12) monoclonal antibody (mAb) and completely inhibited when anti‐IL‐12 mAb and anti‐IL‐18 mAb were used in combination. An aqueous extract of the hemicellulase‐digested compound of A. blazei particle; (ABPC) induced IFN‐γ production more effectively, and this was completely inhibited by anti‐IL‐12 mAb alone. NK cell cytotoxicty was augmented with the same extracts, again in an IL‐12 and IFN‐γ‐dependent manner. These results clearly demonstrated that A. blazei and ABPC augmented NK cell activation through IL‐12‐mediated IFN‐γ production.
Mycobacterium tuberculosis heat‐shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin‐10 production and inhibits T‐cell proliferation in vitro
Authors: Motta Adriana , Schmitz Carla , Rodrigues Luiz , Ribeiro Flávia , Teixeira Cesar , Detanico Thiago , Bonan Carla , Zwickey Heather , Bonorino Cristina
Published: March 2007

In different inflammatory disease models, heat‐shock proteins (hsp) and hsp‐derived peptides have been demonstrated to possess anti‐inflammatory properties. While some studies have shown that hsp can directly interact with antigen‐presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS‐free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS‐free TBhsp70 inhibits murine DC maturation in vitro, while LPS‐contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor‐α production by DC, but interleukin‐10. In vivo, only LPS‐contaminated TBhsp70 induces up‐regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin‐induced T‐cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties.
Clinical amelioration of murine lupus by a peptide based on the complementarity determining region‐1 of an autoantibody and by cyclophosphamide: similarities and differences in the mechanisms of action
Authors: Sharabi Amir , Azulai Hava , Sthoeger Zev M. , Mozes Edna
Published: March 2007

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies and systemic clinical manifestations. In this study we investigated the beneficial effects on murine lupus accomplished by a peptide based on the sequence of the complementarity‐determining region 1 of an anti‐DNA autoantibody (hCDR1) when given alone or in combination with cyclophosphamide (CYC), and determined the mechanisms underlying those effects. SLE‐afflicted (NZB × NZW) F1 mice were treated for 12 weeks with injections of hCDR1, CYC or a combination of both drugs. We found that hCDR1 and CYC ameliorated serological and renal manifestations of the diseased mice, down‐regulated interferon‐γ and interleukin‐10, and up‐regulated transforming growth factor‐β. These effects were associated with an increment of naive CD4+ cells at the expense of the number of CD4+ cells with the memory/activated phenotype. Further, the number of CD8+ cells in the diseased mice was increased by the two drugs, resulting in a significant decrease in the CD4 : CD8 ratio. However, whereas the frequency and activity of CD4+ CD25+ CD45RBlow regulatory T cells and the expression of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) in CD4+ cells were up‐regulated by hCDR1 treatment, they were minimally affected following treatment with CYC. CTLA‐4 played an important role in the activity of the hCDR1‐induced CD4+ CD25+ cells as manifested by down‐regulation of CD28 expression, decrease of activation‐induced apoptosis, and modulation of the cytokine profile in CD4+ CD25– cells derived from SLE‐afflicted mice. Thus, although the two drugs have similar ameliorative effects, hCDR1 but not CYC elicits regulatory pathways that are of importance for tolerance induction in SLE.
Histamine H4 receptor agonists have more activities than H4 agonism in antigen‐specific human T‐cell responses
Authors: Sugata Yuji , Okano Mitsuhiro , Fujiwara Tazuko , Matsumoto Rie , Hattori Hisashi , Yamamoto Miki , Nishibori Masahiro , Nishizaki Kazunori
Published: March 2007

Histamine not only mediates immediate allergic reactions, it also regulates cellular immune responses. H4R is the most recently identified histamine receptor (HR). In the present study, we examined the in vitro effect of histamine and H4R agonists on the responses of human T cells to purified protein derivative from Mycobacterium tuberculosis (PPD) and to Cry j1, the major allergen of Cryptomeria japonica pollen. Dimaprit, clobenpropit and clozapine, which are H4R agonists, dose‐dependently blocked both PPD‐induced interferon‐γ and Cry j1‐induced interleukin‐5 production by both peripheral blood mononuclear cells (PBMCs) and antigen‐specific T‐cell lines. However, the addition of thioperamide, an H3R/H4R antagonist, as well as a mixture of d‐chlropheniramine, famotidine and thioperamide, did not reverse the inhibition. Pretreatment of PBMCs with SQ22536 and 8‐bromoadenosine‐3′,5′‐cyclic monophosphorothioate, Rp‐isomer, had varying abilities to reverse the inhibitory effects of H4R agonists, except for clobenpropit. Moreover, the addition of H4R agonists induced annexin‐V expression on PBMCs, especially in CD19+ and CD4+ cells. cDNA microarray analysis revealed that, among 16 600 genes tested, increased expression following treatment with clozapine was seen in 0·8% of the genes, whereas decreased expression was seen in 3·0% of the genes. These results suggest that H4R agonists inhibit antigen‐specific human T‐cell responses, although H4R does not appear to be important for this effect. In addition, the present study indicated that there may be orphan receptors or HR subtypes which can bind dimaprit, clobenpropit and clozapine, and that can exert an inhibitory effect on antigen‐specific cellular responses via a cAMP/cAMP‐dependent protein kinase‐dependent, apoptotic pathway.
Lost in the present but confident of the past: experiences of being in a psycho‐geriatric unit as narrated by persons with dementia
Authors: Edvardsson David , Nordvall Karin
Published: March 2007

Aim.  To illuminate meanings of being in a psycho‐geriatric unit.

Background.  There are known risks associated with moving persons with dementia from home to an institution, but little is known about how they experience being in psycho‐geriatric units.

Method.  Using open‐ended research interviews, six persons with mild to severe dementia were asked to narrate about their experiences in the hospital. The interviews were interpreted using a phenomenological hermeneutical method of analysis.

Results.  The comprehensive understanding of being in a psycho‐geriatric unit points towards an understanding of being lost in the present but confident of the past. The analysis showed that the participants appeared lost as they could not narrate where they were and why, but that they became confident when narrating about their previous life. The analysis also showed that being in the hospital meant sharing living space with strangers, invasions of private space and establishing new acquaintances. Being in the unit could also mean boredom and devaluation for participants. The interviews were interpreted in the light of narrative theory of identity: persons with dementia narrating about previous life experiences as to make claims of how to be interpreted by others; as persons instead of merely as ‘demented’ patients.

Conclusions.  Experiences of care narrated by persons with dementia present meaningful and useful information that can provide feedback to inform care practice.

Relevance to clinical practice.  Experiences of care from persons with dementia provide meaningful information about care and the doing and being of staff. Creating time for conversations with these persons may facilitate well‐being.
Patients’ self‐report of procedural pain in the intensive care unit
Authors: Siffleet Jo , Young Jeanne , Nikoletti Sue , Shaw Thérèse
Published: March 2007

Aim.  To determine which routine nursing procedures performed on conscious intensive care unit (ICU) patients were painful and which routine procedures were not painful.

Background.  Current empirical evidence supports that routine procedures are often not viewed in the context of causing pain to the critically ill patient. Given the complexity of illness and the need to prioritize care in ICU patients, clinicians may not consider routine procedures as causing pain. With patients in intensive care undergoing frequent routine procedures, greater understanding of which procedures inflict pain is warranted to improve patient care and inform and shape nursing practice.

Design.  A prospective, descriptive study using a convenience sample of ICU patients was used.

Methods.  Sixty‐one patients were asked to rate pain intensity experienced prior to and during a routine nursing procedure using a verbal numeric rating scale. The procedures observed were turning, tracheal suctioning, line removal, deep breathing and coughing exercises, simple dressings and drain removal.

Results.  Results showed that certain routine procedures cause pain with significant differences observed between pre‐ and postprocedure pain scores for drain removal (p = 0·042), deep breathing and coughing exercises (p = 0·003), suctioning (p = 0·025), positional change (p = 0·000) and line removal (p = 0·010). A higher proportion of morphine was administered to those patients undergoing drain removal (50%), deep breathing and coughing exercises (38·5%) and turns (32·6%) but results show that <50% of patients actually received analgesia. Heart rate, systolic and diastolic blood pressure all increased slightly postprocedure but were not found to be statistically significant.

Conclusion.  Haemodynamic measures are not suitable indicators for the presence of pain. Nurses need to recognise that certain routine procedures can cause pain and should therefore plan patient care with this in mind.

Relevance to clinical practice.  Nurses need to recognise of the fact that routine procedures can cause pain and to use analgesia appropriately to minimize this pain. Practice guidelines should recommend that pain relieving measures be considered as part of routine procedural instructions. Analgesic prescription and administration could be improved for this patient group.
Supporting self‐care of patients following general abdominal surgery
Authors: Williams Bev
Published: March 2007

Aims and Objectives.  To determine whether the information people receive following general abdominal surgery is sufficient for them to be able to care for themselves at home in the community.

Background.  Health promotion is a consideration for individuals in all phases of health and illness but little is known about how best to promote health during hospitalization and in the transition from hospital to home in the community.

Methods.  A self‐report questionnaire was used at the point of discharge and a telephone interview was conducted following discharge to determine the adequacy of discharge information received.

Results.  Patients who received information on pain and wound management, activity, nutrition and complications generally felt that it was sufficient at the point of discharge and still felt informed up to three weeks following discharge. Up to 50% of patients did not receive information or received inaccurate formation. The majority of the patients who were given information about pain and wound management did not experience any concerns following discharge. However, many of the patients who did not receive information on pain and wound management experienced concerns that required them to make a non‐routine visit to a health care facility after discharge.

Conclusion.  The findings emphasize the importance of nurses providing specific and accurate verbal and printed discharge information to all patients who have undergone abdominal surgery.

Relevance to Clinical Practice.  Patients who receive accurate and relevant discharge information are less likely to access health care agencies following discharge. Practicing nurses need to ascertain patients’ information needs and nurse educators need to ensure that discharge teaching and self‐care are emphasized in undergraduate nursing curricula.
Aggression and violence in mental health services: categorizing the experiences of Irish nurses
Authors: MAGUIRE J. , RYAN D.
Published: March 2007

There is growing evidence that nurses in mental health services are likely to be victims of violence or aggression. One of the key difficulties in comparing international findings, however, has been that there has been an inadequate categorization of the types of incident to which staff are exposed. The current study aimed to identify the types of violent or aggressive incidents that staff in Irish Mental Health Services were exposed to within a 1‐month long period. A cross‐sectional study was undertaken with all nurses working in one of the Mental Health Services in Ireland, serving both an urban and rural population. Data were collected through a questionnaire (Scale of Aggressive and Violent Experiences) adapted from the Perceptions of Prevalence of Aggression Scale. The questionnaire was designed to collect data relating to both personal and professional demographics of the sample as well as experiences of aggressive or violent incidents respondents may have encountered in their work situation. There was a response rate of 31%. Data were analysed utilizing SPSS‐11. Both descriptive and inferential analyses were undertaken. The relevant data were subjected to a series of one‐way anovas and chi‐squared analysis. The findings suggest that nursing staff in this Mental Health Service experienced high levels of verbal aggression, with distinctions obvious between threatening and non‐threatening aggression, suggesting discernment in terms of intentionality. Additionally, respondents encountered greater levels of covert or indirect violence or aggression than forms that were overtly directed towards staff. The implications are discussed in relation to both policy and practice.
Perspectives on the prevalence and treatment of personality disorder
Authors: WINSHIP G. , HARDY S.
Published: March 2007

Personality disorder (PD) is the most prevalent psychiatric disorder. A methodical literature search identified that PD is under researched compared with other mental health problems such as depression or schizophrenia. Social and psychotherapeutic approaches emerge as dominant treatment approaches with PD where there is good evidence of efficacy. Collaborative group‐based therapeutic approaches appear to offer a therapeutic counterpoise to the anti‐social traits often prevalent in PD. A retrospective analysis of formal group therapy on acute inpatient units (treating PD patients among other mental health disorders) reveals only one violent incident in over 40 000 treatment hours of formal group therapy. It is argued that group‐based and social therapy should be the recommended treatment approach because these approaches have been shown to create a safe and contained milieu, establishing a good base for therapeutic gain with PD patients. The case for widening the scope of collaborative group and community‐based therapies is considered and the merits and shortcomings of a key worker system with PD patients are critiqued.
Exploring the relationship between perceived emotional intelligence, coping, social support and mental health in nursing students
Authors: MONTES‐BERGES B. , AUGUSTO J.‐M.
Published: March 2007

Studies conducted with nurses or nursing students have shown that emotional intelligence is a skill that minimizes the negative stress consequences. The present work examines the role of perceived emotional intelligence (PEI) measured by the Trait Meta‐Mood Scale, in the use of stress‐coping strategies, in the quantity and quality of social support and in the mental health of nursing students. The results indicated positive correlations between clarity and social support, social support and repair, and social support and mental health. Hierarchy regression analysis pointed out that clarity and emotional repair are predictors of social support, and emotional repair is the main predictor of mental health. These results show the importance of PEI in stress coping within the nursing framework.
A national survey of community psychiatric nurses and their client care activities in Ireland
Authors: MCCARDLE J. , PARAHOO K. , MCKENNA H.
Published: March 2007

Increasingly, people with mental health problems in Ireland and in the UK are receiving mental health services in the community. The aim of this study was to identify the predominant approaches to care used by community psychiatric nurses (CPNs) and the theoretical bases of their practice. One hundred and sixteen questionnaires out of 203 sent to CPNs throughout Ireland were returned, giving a response rate of 57.1%. In addition, 33 home visits by 13 CPNs were observed. The findings showed that over 96% of the sample were in full‐time employment; most (71.4%) worked a 9–5 weekday shift; 31% had a postregistration counselling qualification, and about a quarter were based in hospitals. The average caseload size was 61 and the service was predominantly a closed referral one. The main client care activities were: assessment of clients, medication management, health promotion, and client and family support. From the observations, there was no evidence of CPNs practising cognitive, behaviour therapy or family therapies to any great extent. This study provides baseline data for monitoring trends in community mental health nursing in Ireland, and for informing future policy regarding service provision and training of CPNs.
Transference in the nurse–patient relationship
Authors: EVANS A. M.
Published: March 2007

The therapeutic relationship has been considered foundational to psychiatric nursing practice since at least the mid‐20th century. However, this does not, in itself, guarantee either its continuity or relevance to current practice. Concepts such as the therapeutic relationship require sustained attention, both in theory and in practice, to illustrate ongoing relevance to the discipline. This paper addresses the therapeutic relationship in psychiatric nursing via aspects of psychoanalytic theory, particularly the notion of transference, as theorized by both Freud and Lacan. Two case fragments provide practice material, through which transference in the nurse–patient relationship is explored. The nurse, in the context of his/her relationship with the patient, a sick stranger, offers both a listening and the potential development of transference. This transference can be experienced, in part, as a form of attachment to the nurse, one that is not regarded pejoratively as dependency. There is the potential, within the nurse–patient relationship, for a psychical holding to develop, one from within which both the patient can speak and transference might arise. It is argued that listening to the patient has the potential to assist the patient and, with the development of transference, can provide the context for important work.
Surveying the attitudes of acute mental health nurses
Authors: MUNRO S. , BAKER J. A.
Published: March 2007

Recent UK policy and guidance indicates the importance of positive attitudes towards mental health service users. This is especially true in acute inpatient care, where service users are often at their most vulnerable and have higher levels of contact with mental health staff. The following paper details secondary analysis of data collected for the validation of an attitude measurement scale with a sample of 140 nursing staff in acute settings. The results demonstrate that a wide range of attitudes are held by mental health nurses towards acute mental health care. Overall, the results indicate generally positive attitudes. Significant differences were found between qualified and unqualified staff, and males and females for some questions. Recommendations are made for future attitudinal research of mental health staff.
Early intervention in psychosis: a rural perspective
Authors: KELLY M. , O’MEARA HOWARD A. , SMITH J.
Published: March 2007

Over the past decade, there has been great interest in both the development and delivery of early intervention in psychosis services in the United Kingdom, supported by national policy and a Policy Implementation Guide (PIG). Despite this, the PIG fails to distinguish the delivery of early intervention services to different population groups. The paper aims to augment available literature with the range of complex issues that practitioners may face when working in rural settings and link this to the development of early intervention services in rural communities. This paper will also outline some of the fundamental factors that challenge delivery of early intervention to individuals with a first episode of psychosis and their families in rural communities. Important key areas for consideration will be highlighted for both the planning and delivery of early intervention to rural communities.
The Keele–Exeter young cluster survey – I. Low-mass pre-main-sequence stars in NGC 2169
Authors: Jeffries R. D. , Oliveira J. M. , Naylor Tim , Mayne N. J. , Littlefair S. P.
Published: March 2007

We have used RCIC CCD photometry from the Isaac Newton telescope and intermediate-resolution spectroscopy from the Gemini North telescope to identify and characterize low-mass (0.15 < M/M⊙ < 1.3) pre-main-sequence stars in the young open cluster NGC 2169. Isochrone fitting to the high- and low-mass populations yields an intrinsic distance modulus of 10.13+0.06−0.09 mag and a model-dependent age of 9 ± 2 Myr. Compared to the nearby, kinematically defined groups of a similar age, NGC 2169 has a large low-mass population which potentially offers a more precise statistical investigation of several aspects of star formation and early stellar evolution. By modelling the distribution of low-mass stars in the IC versus RC−IC diagram, we find that any age spread among cluster members has a Gaussian full width at half-maximum (FWHM) ≤ 2.5 Myr. A young age and a small age spread (<10 Myr) are supported by the lack of significant lithium depletion in the vast majority of cluster members. There is no clear evidence for accretion or warm circumstellar dust in the low-mass members of NGC 2169, bolstering the idea that strong accretion has ceased and inner discs have dispersed in almost all low-mass stars by ages of 10 Myr.
Validation of CADESI‐03, a severity scale for clinical trials enrolling dogs with atopic dermatitis
Authors: Olivry Thierry , Marsella Rosanna , Iwasaki Toshiroh , Mueller Ralf ,   The International Task Force On Canine Atopic Dermatitis
Published: March 2007

In dogs, atopic dermatitis (AD) is a common and chronic allergic skin disease that often necessitates treatment with pharmacological interventions. In the last 30 years, numerous clinical trials testing the efficacy of anti‐inflammatory drugs have been reported, but there has been a lack of consistency in the assessment of outcome measures. Several clinical scales have been employed over time, but none of these scoring systems were ever tested for validity and reliability. A committee of the International Task Force on Canine Atopic Dermatitis evaluated the currently available scales used to assess disease morbidity in humans and dogs with AD, and a third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI‐03) was designed. This version was expanded from previous ones by redistribution and increase in body sites tested, the use of an additional lesion reflecting underlying pruritus (e.g. self‐induced alopecia) and an increase in the numerical range of severity for each lesion. The CADESI‐03 scale was tested for validity and reliability in a cohort of 38 dogs with AD. Overall, this revised version of the CADESI was found to exhibit acceptable content, construct, criterion, and inter‐ and intra‐observer reliability and sensitivity to change. As a result, this scale is recommended as a validated tool for assessment of disease severity in clinical trials testing the efficacy of interventions in dogs with AD.
Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes
Authors: Bäumer Wolfgang , Kietzmann Manfred
Published: March 2007

The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human atopic dermatitis. Their direct impact on keratinocytes, especially canine keratinocytes, is less obvious. Thus, an investigation was carried out to ascertain whether cyclosporin A and cilomilast modulate keratinocyte proliferation and secretion of proinflammatory mediators. Cyclosporin A inhibited canine and murine keratinocyte proliferation, whereas cilomilast had no affect. Cyclosporin A and cilomilast reduced the lipopolysaccharide‐induced prostaglandin E2 synthesis in canine and murine keratinocytes. Both immunomodulators also inhibited the production of the CXC chemokine KC and CCL2 in the murine keratinocyte cell line MSC‐P5. The two immunomodulators also significantly reduced the interferon‐γ‐induced production of interferon‐γ‐inducible protein 10 in human keratinocytes (HaCaT cells). Thus, cyclosporin A and cilomilast directly modulate keratinocyte functions which might contribute to the anti‐inflammatory and immunomodulatory action of these compounds in the treatment of allergic skin diseases.
Variability of laboratory identification and antibiotic susceptibility reporting ofPseudomonasspp. isolates from dogs with chronic otitis externa
Authors: Schick Anthea E. , Angus John C. , Coyner Kimberly S.
Published: March 2007

The purpose of this study was to evaluate interlaboratory variation in isolation and antibiotic susceptibility pattern ofPseudomonasspp. as reported to veterinarians for cases of canine chronic bacterial otitis externa. Twenty‐six dogs with unilateral or bilateral bacterial otitis externa from multiple referral practices were included in this prospective study. Triplicate samples collected simultaneously from the same location in the external ear canal were randomly submitted to three laboratories for culture and susceptibility testing.Pseudomonasspp. were isolated from 18 of 34 (53%) ears. All three laboratories agreed on the presence ofPseudomonasspp. in 15 (83.3%) ears sampled. However, two laboratories agreed on two (11.1%) occasions, and on one occasion (5.5%)Pseudomonasspp. were identified in only one laboratory. Minimum inhibitory concentration (MIC) susceptibilities to 11 antibiotics were compared between laboratories B and C. Using laboratory‐defined susceptibility of sensitive (S), intermediate (I) and resistant (R), none of the 16Pseudomonasspp. with MIC data reported had identical patterns of antibiotic susceptibility. Agreement in susceptibility to individual antibiotics was observed in 13 of 16 (81%) occasions for amikacin and gentamicin, 10 of 16 (63%) occasions for ticarcillin, and nine of 16 (56%) for enrofloxacin. These results indicate thatPseudomonasspp. were identified by all three laboratories chosen for this study in 83% of the time. Moreover, antibiotic susceptibility patterns and MIC values reported to veterinarians may not agree between laboratories. Veterinarians should interpret bacterial culture and susceptibility results with multiple caveats including variability between laboratories.
Prioritization and resource allocation in health care. The views of older people receiving continuous public care and service
Authors: Werntoft Elisabet , Hallberg Ingalill R. , Edberg Anna‐Karin
Published: March 2007

Objective  To describe the views of people, 65 years and over, receiving continuous public care and service, on prioritization and resource allocation in health care, in relation to gender, age, housing, health‐related quality of life (QoL) and degree of activities of daily living (ADL) dependency.

Background  How older people receiving continuous public care and service view prioritization and resource allocation in health care is sparsely investigated, although this group most certainly has the experience and also often is the target in discussions concerning prioritization. It is necessary, for democracy and for the development of new models of service delivery, to find out how people receiving long‐term care and service view these issues.

Design  146 persons, 34 men (23%) and 112 women (77%), aged 66–100 years were interviewed face to face, following a structured questionnaire.

Results  The respondents thought that the patients’ well‐being, way of living and family situation should affect prioritization, not age per se. Resourcing of several health‐care services were considered to be below what is required by a majority of the respondents. The respondents wanted doctors to decide on prioritization at an individual level and wanted higher taxes to finance increasing health‐care costs. Although the respondents wanted publicly financed health care, a relatively high number were willing to pay for treatment.

Conclusions  Knowledge of how older people receiving care and services, view prioritization and resource allocation has not previously been available. It seems that their views are in line with the Swedish Parliamentary Priority Commission which suggested that no account should be taken of age when allocating resources within the health‐care system. Respondents’ age, gender, housing, health‐related QoL and degree of dependency in ADL had limited influence on their views of resource allocation.
Patient and public involvement: What next for the NHS?
Authors: Hogg Christine N. L.
Published: March 2007

Introduction  Patient and public involvement is the cornerstone of the ‘patient‐led’ National Health Service (NHS). Though the UK has had state sponsored arrangements for patient and public involvement since 1974, they have become fragmented and unstable. Patients’ forums and the Commission for Patient and Public Involvement in Health replaced community health councils (CHCs) and their national association in England in 2003, but now will be replaced by local involvement networks (LINks) and the Commission will be abolished in 2007.

Learning from history  This study provides an overview of research on the effectiveness of arrangements for patient and public involvement and reviews the debates about accountability, independence, ensuring consistency of performance, representation and how arrangements for the NHS fit within the wider agenda of citizenship and renewal of democracy. It explores key themes and areas for learning to inform the debate about how LINks might work effectively to improve the health of local people, in particular addressing issues of equity, representation and citizen engagement.

Conclusions  The proposed LINks provide the opportunity to integrate patient and public involvement into wider initiatives for local democracy and citizen engagement. But debates and key issues about user and public involvement in the 1970s remain current and unresolved. If the new LINks are to succeed where forums and CHCs are considered to have failed, the strengths and weakness of both need to be understood and addressed.
PhadiatopTM compared to skin‐prick test as a tool for diagnosing atopy in epidemiological studies in schoolchildren
Authors: Garcia‐Marcos Luis , Sanchez‐Solis Manuel , Martinez‐Torres Antonia E. , Lucas Moreno Jose M. , Sastre Vicente Hernando
Published: March 2007

The validity of the PhadiatopTM test as compared to the skin‐prick test (SPT) for diagnosing atopy in the epidemiological field has not been studied in schoolchildren. The aim of the present study was to evaluate its validity for classifying schoolchildren 9–12 yr old into atopics and non‐atopics. A total of 621 children whose parents authorized both a SPT and a blood extraction from all children participating in the phase II of the International Study of Allergies in Children (ISAAC) in Cartagena (Spain) were included in the analysis. A positive SPT was that with at least a wheal having a maximum diameter of 3 mm, once the negative value had been subtracted. PhadiatopTM was performed according to the manufacturer instructions. Diagnostic tests using SPT as the gold standard were calculated for the whole group of children and also for those with asthma or rhinoconjunctivitis and for children without any of them. The results of the tests were: sensitivity 85.0% (95% CI 82.2–87.8%), specificity 85.5% (95%CI 82.7–88.3%), positive predictive value 72.7% (95%CI 69.0–76.1%), negative predictive value 92.7% (95%CI 90.6–94.7%) and accuracy 85.3% (95%CI 82.3–88.0%). The results improved among the symptomatic groups. PhadiatopTM can be used as a valid alternative to SPT in the epidemiological setting to diagnose atopy.
Serum levels of vascular endothelial growth factor in children and adolescents with systemic lupus erythematosus
Authors: Heshmat Nahla M. , El‐Kerdany Tahany H.
Published: March 2007

The angiogenic cytokine vascular endothelial growth factor (VEGF) may have a role in the pathogenesis of collagen diseases. We aimed to assess its serum levels in children and adolescents with systemic lupus erythematosus (SLE) and to elucidate its correlation with clinical features, laboratory parameters, and the overall disease activity. This study comprised 25 children and adolescents with SLE and 30 healthy controls. Disease activity was evaluated by SLE disease activity index (SLEDAI) score. Laboratory investigations included complete blood count, erythrocyte sedimentation rate (ESR), urine analysis, 24‐h total urinary protein, assay of serum creatinine, ANA, anti‐DNA, complement component C3, lupus anticoagulant, and VEGF. Serum levels of VEGF were significantly increased in SLE patients (579.5 ± 184.7 pg/ml) when compared with controls (113.2 ± 30.8 pg/ml) (p < 0.0001). VEGF serum levels were significantly increased in patients having renal involvement and neurologic symptoms than those who did not have them (p < 0.0001, p < 0.005, respectively). Serum levels of VEGF were higher in patients with antiphospholipid syndrome, vasculitis, and skin symptoms than those without, but the difference did not reach statistical significance. Meanwhile, they were similar in patients with and without arthritis (p > 0.05). VEGF serum levels were not correlated to age; inversely correlated to platelet count, serum C3 level; and positively correlated to ESR. SLEDAI score was positively correlated to VEGF serum level (r = 0.86, p < 0.0001). VEGF may be relevant to SLE pathogenesis. Its concentration seems to be a marker of SLE activity, which could help in disease monitoring and planning of treatment.
Action of a silk fabric treated with AEGISTM in children with atopic dermatitis: A 3‐month trial
Authors: Koller D. Y. , Halmerbauer G. , Böck A. , Engstler G.
Published: March 2007

Irritation of the skin of patients with atopic dermatitis by contact with rough fibres of synthetic or woollen clothes is well known. Therefore, it has been recommended that patients should wear cotton clothes. However, cotton also consists of rough fibres able to irritate the skin, whereas silk is characterized by smooth fibres without irritating potential. The aim of our study was to evaluate the clinical effect of Dermasilk®– a special silk fabric (sericin‐free silk treated with AEGIS AEM5772/5 which has antibacterial properties) – in children with atopic dermatitis. A total of 22 children with mild‐to‐moderate atopic dermatitis were recruited for a study period of 3 months. All of them received three different tube‐fabrics – Dermasilk, sericin‐free silk fabric without AEGIS AEM 5772/5 and cotton, covering the cubital region. Patients were advised to wear the Dermasilk fabric all day long during the whole study period on one arm, whereas the sericin‐free AEGIS‐free silk tube had to be used during the first 2 wk only on the other arm followed by the use of the cotton tube for the rest of the study period. Evaluation of the local SCORAD score was carried out at the beginning of the study, after 2, 4, 8 and 12 wk. A significant reduction of the local SCORAD index of the Dermasilk covered arm was observed after 4, 8 and 12 wk in comparison with the cotton‐covered arm score [median (quartile 1–quartile 3)] 6.5 (5–8) vs. 8 (7–9), p < 0.002; 6 (5.25–7.75) vs. 8 (7–9), p < 0.0001; and 6 (5–6) vs. 8 (7.25–10), p < 0.0001. The use of Dermasilk has a significant beneficial effect in atopic dermatitis because of the non‐irritating properties of silk as well as the antibacterial capacity of AEGIS AEM 5772/5.
IgE and atopy in perinatally HIV‐infected children
Authors: Bowser Corinna S. , Kaye Jean , Joks Rauno O. , Charlot Cascy‐Arnoux , Jack Moallem H.
Published: March 2007

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV‐infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV‐disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV‐infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non‐atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV‐infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.