bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of inhibitor titres by infusion of FVIII gene transduced tolerogenic dendritic cells in haemophilic mice
Authors: SU RUI‐JUN , EPP ANGELA , WU XIAOPING , JOSEPHSON NEIL C. , PIPE STEVEN W.
Published: March 2009

Background:  The development of anti‐factor VIII (FVIII) inhibitory antibodies is a major complication of FVIII replacement therapy in the management of patients with haemophilia A. Evidence is accumulating that tolerogenic dendritic cells (tDCs) generated in vitro can induce regulatory T cells and promote durable antigen‐specific tolerance in vivo.

Objective:  In this study we used human FVIII transgene expressing tDCs to reduce inhibitor formation in haemophilic mice.

Methods and results:  The tDCs were generated by cell sorting the CD11clowCD45RBhigh population of cells resulting from culture of lineage negative bone marrow cells in media supplemented with IL‐10 and the neural peptides VIP and PACAP38. Expression of co‐stimulatory molecules CD40, CD80 and CD86 and MHC Class II was negative or low on these cells and they remain unactivated even after stimulation with lipopolysaccharide (LPS) or transduction by foamy virus (FV) vectors. Following transduction by a FV vector expressing a B domain deleted human FVIII transgene, 3–5 × 105 tDCs were infused by tail vein injection into Bal/c haemophilic mice (tDC‐F8) weekly for two doses. Real‐time PCR showed that the transduction efficiency of our FV vector in this population of tDCs was approximately 70%. Subsequently, mice were challenged with four weekly intravenous doses of 0.2 μg rhFVIII. Mice that received no cells (Neg‐Ctrl) and mice that received an equivalent number of non‐transduced tDCs (tDC‐Ctrl) were used as controls. After immunization with rhFVIII, the spleen size, weight and total cell numbers in tDC‐F8 mice were consistently lower than in Neg‐Ctrl and tDC‐Ctrl mice by approximately 50%. Flow cytometry assessment of CD4+ splenocytes showed there were an increased number of cells expressing the regulatory T‐cell markers FOXP3, CD25, CD103, CTLA4 and GITR in tDC‐F8 treated mice. We observed a 60% and 61% reduction in the level of inhibitor titres from tDC‐F8 mice compared with Neg‐Ctrl and tDC‐Ctrl mice. Splenic CD4+ T cell proliferation in response to FVIII stimulation in cells from tDC‐F8 mice was suppressed by approximately 90% compared with proliferation of cells from Neg‐Ctrl and tDC‐Ctrl mice. We also showed that pre‐immunized mice treated with four infusions of hFVIII FV vector transduced tDCs had a reduction in their inhibitor titres by 54% (P < 0.05). No significant change in inhibitor titres were seen in untreated controls or mice given four doses of untransduced tDCs.

Summary:  These data indicate that hFVIII gene transduced tolerogenic DCs are useful in decreasing inhibitory antibodies in haemophilic mice. More in vivo studies are in progress to confirm the antigen‐specificity and durability of these effects. Our future studies will focus on isolating and characterizing the regulatory T cell populations induced by in vivo administration of transgene modified tDCs.
Recurrence of inhibitor after orthotopic liver transplantation in severe haemophilia A
Authors: STABLER SALLY , RISKE BRENDA , GERAGHTY SUE
Published: March 2009

Objective:  Orthotopic liver transplantation (OLT) treats both hepatitis C‐associated cirrhosis and haemophilia A with factor VIII activity increasing into the normal range in most patients. However, the results of OLT in haemophilia patients with inhibitors have been mixed. We report the follow‐up factor VIII values after OLT in an inhibitor patent.

Methods:  A middle‐aged white male with severe haemophilia A, who had been on immune tolerance for >10 years for a high‐responding factor VIII inhibitor underwent OLT. Factor VIII activity and inhibitor titres were followed over the next 9 months.

Summary:  The patient had received factor VIII 40 u kg−1 three times/week for many years, which suppressed inhibitor titres to <2 BU. Higher doses of factor had been used to support him through surgery with good results. At the time of OLT, his inhibitor titre was 0.7BU. He was treated prior to transplant surgery with 116 u kg−1 with smaller doses every 2–4 h with monitoring during the operation. In the next 24 h he required another 300 u kg−1 of factor VIII to maintain activity between 61–122%. On postop days 1 and 2 he received 46 and 35 u kg−1 to maintain mean activity of about 50%. Around Day 6 his requirement for factor VIII increased to 70 u kg−1 daily to maintain the same levels. He was treated for possible acute liver rejection with high dose Solu–Medrol and his requirements for factor VIII decreased so that it was discontinued on day 13 postop. Over the next month, his factor VIII activity increased from 57–91% and he had no bleeding complications. Immune suppression was achieved with tacrolimus, mycophenolate and prednisone, the latter being discontinued about 1 month post OLT. After a peak of factor VIII activity at one month, his level decreased so that it was 52% and 37% at 4 and 6 months, respectively, despite the continuous use of immunosuppression for the OLT. Seven months after transplant, the patient underwent a procedure with a prefactor VIII infusion activity of 25% and a 2 h postinfusion activity of 71% after receiving 50 u kg−1. The Bethesda titre for the inhibitor was 0.9 units at this time. The most recent factor activity has dropped to 19% at 9 months. The patient has not had any bleeds post‐transplantation, however.

Conclusions:  1. An inhibitor patient on long‐term immune tolerance underwent successful orthotopic liver transplantation with initial normalization of factor VIII activity.

2. Beginning 2 months after OLT and continuing to the present, factor VIII activity gradually decreased associated with detection of a low titre recurrent factor VIII inhibitor.

Synthesis of factor VIII by the donor liver is not sufficient for total suppression of the long‐standing inhibitor.
Discrimination between the main activating and inhibitory killer cell immunoglobulin‐like receptor positive natural killer cell subsets using newly characterized monoclonal antibodies
Authors: David Gaëlle , Morvan Maelig , Gagne Katia , Kerdudou Nolwenn , Willem Catherine , Devys Anne , Bonneville Marc , Folléa Gilles , Bignon Jean‐Denis , Retière Christelle
Published: March 2009

Natural killer (NK) cells are key components of the innate anti‐viral and anti‐tumour immune responses. NK cell function is regulated by the interaction of killer cell immunoglobulin‐like receptors (KIR) with human leucocyte antigen (HLA) class I molecules. In this study, we report on the generation of KIR‐specific antibodies allowing for discrimination between activating and inhibitory KIR. For this purpose, BALB/c mice were immunized with human KIR2DS2 recombinant protein. The precise specificity of KIR2DS2‐specific clones was determined on KIR‐transfected BW cells and KIR‐genotyped NK cells. When used in combination with EB6 (KIR2DL1/2DS1) or GL183 (KIR2DL2/2DL3/2DS2), two KIR‐specific monoclonal antibodies (mAbs), 8C11 (specific for KIR2DL1/2DL2/2DL3/2DS2) and 1F12 (specific for KIR2DL3/2DS2), discriminated activating KIR2DS1 (8C11− EB6+) from inhibitory KIR2DL1 (8C11+ GL183−) and KIR2DL2 (1F12− GL183+), while excluding the main HLA‐Cw‐specific KIR. Using these mAbs, KIR2DS1 was shown to be expressed on the surface of NK cells from all individuals genotyped as KIR2DS1+ (n = 23). Moreover, KIR2DS1 and KIR2DL1 were independently expressed on NK cells. We also determined the amino acid position recognized by the 8C11 and 1F12 mAbs, which revealed that some KIR2DL1 allele‐encoded proteins are not recognized by 8C11. Because most available anti‐KIR mAbs recognize both inhibitory and activating forms of KIR, these newly characterized antibodies should help assess the expression of activating and inhibitory KIR and their functional relevance to NK biology.
Identification of a novel murine pancreatic tumour antigen, which elicits antibody responses in patients with pancreatic carcinoma
Authors: Zhao Fei , Vermeer Benjamin , Lehmann Ulrich , Kreipe Hans , Manns Michael P. , Korangy Firouzeh , Greten Tim F.
Published: March 2009

Pancreatic cancer is the fourth leading cause of cancer related death in the United States. Despite numerous efforts in developing new therapies, the prognosis for patients with pancreatic cancer remains poor. Mouse models for spontaneous pancreatic cancer represent an ideal system to develop immunotherapeutic approaches. The aim of this study was to identify new tumour antigens in a murine model that mimics human disease closely, and to verify the results in patients with pancreatic cancer. We analysed a murine pancreatic complementary DNA expression library with serum from tumour‐bearing mice, which led to the identification and isolation of several antigens. One of the antigens repeatedly identified in this screening was Tankyrase‐2. Here, we show Tankyrase‐2 as an antigen eliciting humoral responses not only in mice with established tumours, but also in mice with pre‐malignant lesions. Finally, antibody responses to Tankyrase‐2 were found in the serum of patients with pancreatic cancer. Reverse transcriptase–polymerase chain reaction analysis showed Tankyrase‐2 expression in human pancreatic tumour. These findings show the relevance of spontaneous murine tumour models for the identification of human tumour antigens.
MicroRNA in the immune system, microRNA as an immune system
Authors: Lu Li‐Fan , Liston Adrian
Published: March 2009

The advent of microRNA has potentially uncovered a new level of complexity to be considered for every biological process. Through the modulation of transcription and translation, microRNA alter the basal state of cells and the outcome of stimulatory events. The exact effect of the microRNA network and individual microRNA on cellular processes is only just starting to be dissected. In the immune system, microRNA appear to have a key role in the early differentiation and effector differentiation of B cells. In T cells, microRNA have been shown to be key regulators of the lineage induction pathways, and to have a strong role in the induction, function and maintenance of the regulatory T‐cell lineage. MicroRNA are also important for regulating the differentiation of dendritic cells and macrophages via toll‐like receptors, with responsibilities in suppressing effector function before activation and enhancing function after stimulation. In addition to regulating key processes in the immune system, microRNA may also represent an archaic immune system themselves. Small interfering RNA of viral origin has been shown to function as an intracellular mediator in the suppression of viral infection in eukaryotes as diverse as plants, insects, nematodes and fungi, and there is growing evidence that endogenous mammalian microRNA can have similar impacts. In this article we speculate that the anti‐viral function of microRNA drove the expression of different subsets of microRNA in different cellular lineages, which may have, in turn, led to the myriad of roles microRNA play in lineage differentiation and stability.
Oral health programme for preschool children: a prospective, controlled study
Authors: MEURMAN PIA , PIENIHÄKKINEN KAISU , ERIKSSON ANNA‐LEENA , ALANEN PENTTI
Published: March 2009

Background.  New perspectives are needed for oral health programmes (OHPs). The aim was to evaluate the preventive effect of a risk‐based OHP in comparison with a traditional programme.

Design.  An age cohort of 794 Finnish children, 446 in the intervention group and 348 in the control group, was followed from 18 months to 5 years of age. The children were screened for mutans streptococci (MS) in the dental biofilm. The main outcome measure was the proportion of children with dental caries (decayed, missing, or filled primary teeth > 0) at the age of 5 years. The intervention, targeted to MS‐positive subjects in the intervention group only, was based on repeated health education to the caretakers and xylitol lozenges for the child. Dental hygienists carried out the programme.

Results.  OHP was effective in white‐collar families [numbers needed to treat (NNT) = 3, 95% CI 2–11]. Factors significantly associated with caries at 5 years were MS colonization at 18 months, occupation of caretaker, but also gender when incipient carious lesions were included in the index.

Conclusion.  Early risk‐based OHP, targeted to the families of MS‐positive children, can reduce the risk for caries in white‐collar families. For blue‐collar families, different kinds of methods in caries prevention and support are needed.
Inclusion of soil data improves the performance of bioclimatic envelope models for insect species distributions in temperate Europe
Authors: Titeux Nicolas , Maes Dirk , Marmion Mathieu , Luoto Miska , Heikkinen Risto K.
Published: March 2009

Aim To analyse the effect of the inclusion of soil and land‐cover data on the performance of bioclimatic envelope models for the regional‐scale prediction of butterfly (Rhopalocera) and grasshopper (Orthoptera) distributions.

Location Temperate Europe (Belgium).

Methods Distributional data were extracted from butterfly and grasshopper atlases at a resolution of 5 km for the period 1991–2006 in Belgium. For each group separately, the well‐surveyed squares (n = 366 for butterflies andn = 322 for grasshoppers) were identified using an environmental stratification design and were randomly divided into calibration (70%) and evaluation (30%) datasets. Generalized additive models were applied to the calibration dataset to estimate occurrence probabilities for 63 butterfly and 33 grasshopper species, as a function of: (1) climate, (2) climate and land‐cover, (3) climate and soil, and (4) climate, land‐cover and soil variables. Models were evaluated as: (1) the amount of explained deviance in the calibration dataset, (2) Akaike’s information criterion, and (3) the number of omission and commission errors in the evaluation dataset.

Results Information on broad land‐cover classes or predominant soil types led to similar improvements in the performance relative to the climate‐only models for both taxonomic groups. In addition, the joint inclusion of land‐cover and soil variables in the models provided predictions that fitted more closely to the species distributions than the predictions obtained from bioclimatic models incorporating only land‐cover or only soil variables. The combined models exhibited higher discrimination ability between the presence and absence of species in the evaluation dataset.

Main conclusions These results draw attention to the importance of soil data for species distribution models at regional scales of analysis. The combined inclusion of land‐cover and soil data in the models makes it possible to identify areas with suitable climatic conditions but unsuitable combinations of vegetation and soil types. While contingent on the species, the results indicate the need to consider soil information in regional‐scale species–climate impact models, particularly when predicting future range shifts of species under climate change.
The curse of taxonomic uncertainty in biogeographical studies of free‐living terrestrial protists: a case study of testate amoebae from Amsterdam Island
Authors: Heger T. J. , Mitchell E. A. D. , Ledeganck P. , Vincke S. , Van de Vijver B. , Beyens L.
Published: March 2009

Aim  A current debate in microbial biogeography contrasts two views concerning the distribution of free‐living microorganisms. The first view assumes a ubiquitous distribution, while the second assumes that at least some species have limited geographical distributions. We tested for limited geographical distributions by identifying testate amoebae morphospecies from an extremely remote oceanic island where the potential for endemism is high.

Location  Amsterdam Island, Indian Ocean.

Methods  Sixty moss and water samples collected from the top of the volcano to the lowland were investigated for their testate amoeba content. Due to taxonomic uncertainties among the Argynnia (Nebela) dentistoma species complex (including A. antarctica), we also performed light and scanning electron microscopy investigations on the shell ultrastructure and biometric analyses on several specimens of this taxon.

Results  We identified a total of 43 testate amoeba taxa belonging to 15 genera. Only four testate amoeba taxa had previously been recorded on this island. Testate amoeba communities of Amsterdam Island are dominated by cosmopolitan ubiquitous euglyphid taxa such as Trinema lineare, Assulina muscorum and Corythion dubium. The length and width ranges for Argynnia dentistoma on Amsterdam Island overlap with other records of this species and of A. antarctica, suggesting that A. antarctica is not a distinct taxon.

Main conclusions  Although Amsterdam Island is among the most remote islands in the world, an extensive inventory of testate amoeba morphospecies provided no clear evidence for endemism. On the one hand, our detailed morphometric analysis of the A. dentistoma complex revealed that A. antarctica, a morphospecies previously suggested to display endemism, cannot be confidently distinguished from the cosmopolitan morphospecies A. dentistoma. On the other hand, five morphotaxa could not be identified with certainty and might represent new species, potentially with limited distribution. These examples illustrate how taxonomic uncertainties undermine biogeographical studies of testate amoebae. In order to allow better interpretation of morphology‐based testate amoeba distribution data, an assessment of genetic diversity among and within morphotaxa in relation to geographical distance for some common testate amoebae should be given high priority.
Possible Role of Oestrogen in Pubertal Increase of Kiss1/Kisspeptin Expression in Discrete Hypothalamic Areas of Female Rats
Authors: Takase K. , Uenoyama Y. , Inoue N. , Matsui H. , Yamada S. , Shimizu M. , Homma T. , Tomikawa J. , Kanda S. , Matsumoto H. , Oka Y. , Tsukamura H. , Maeda K.‐I.
Published: March 2009

Kisspeptin, a peptide encoded by the Kiss1 gene, has been considered as a potential candidate for a factor triggering the onset of puberty, and its expression in the hypothalamus was found to increase during peripubertal period in rodent models. The present study aimed to clarify the oestrogenic regulation of peripubertal changes in Kiss1 mRNA expression in the anteroventral periventricular nucleus (AVPV) and hypothalamic arcuate nucleus (ARC), and to determine which population of kisspeptin neurones shows a change in kisspeptin expression parallel to that in luteinising hormone (LH) pulses at the peripubertal period. Quantitative reverse transcriptase‐polymerase chain reaction and immunohistochemistry revealed an apparent increase in the ARC Kiss1 mRNA expression and kisspeptin immunoreactivity around the time of vaginal opening in intact female rats. The AVPV Kiss1 mRNA levels also increased at day 26, but decreased at day 31, and then increased at day 36/41. In ovariectomised (OVX) rats, ARC Kiss1 mRNA expression did not show peripubertal changes and was kept at a high level throughout peripubertal periods. Apparent LH pulses were found in these prepubertal OVX rats. Oestradiol replacement suppressed ARC Kiss1 mRNA expression in OVX prepubertal rats, but not in adults. Similarly, LH pulses were suppressed by oestradiol in the prepubertal period (days 21 and 26), but regular pulses were found in adulthood. The present study suggests that a pubertal increase of Kiss1/kisspeptin expression both in the ARC and AVPV is involved in the onset of puberty. These results also suggest that both LH pulses and ARC Kiss1 expression are more negatively regulated by oestrogen in prepubertal female rats compared to adult rats.
Puberty Onset in Female Rats: Relationship With Fat Intake, Ovarian Steroids and the Peptides, Galanin and Enkephalin, in the Paraventricular and Medial Preoptic Nuclei
Authors: Leibowitz S. F. , Akabayashi A. , Alexander J. , Karatayev O. , Chang G.‐Q.
Published: March 2009

Puberty is a time of rapid change, including a marked increase in fat consumption and body fat accrual, particularly in females. The mechanisms underlying these changes are unknown. Building on the results obtained in adult rats, the present study in pubertal rats focused on the orexigenic peptides, galanin (GAL) and enkephalin (ENK), in the paraventricular nucleus (PVN) and medial preoptic nucleus (MPN), which are known to be responsive to female steroids and have a role in both energy balance and reproductive function. The present study examined female rats maintained on pure macronutrient diets from before weaning (day 15) to day 70. After an initial burst in protein intake (days 21–35), rats showed an increase, specifically in preference for fat, from 15% to 30%. In rats examined at different ages before (day 30) and after (days 45 and 60) puberty, this rise in fat intake was associated with a marked increase, from days 30–45, in levels of oestradiol and progesterone and in GAL and ENK mRNA or peptide levels, specifically in the PVN and MPN, but not other hypothalamic areas examined. This positive relationship with increased fat intake, steroids and peptides across ages was also observed when comparing pubertal rats that naturally preferred fat (> 25% of total diet) with those consuming little fat (< 15%) or rats that reached puberty at an early age (days 30–34) with those that were late (days 37–40). These rats with early puberty onset exhibited a strong fat preference 3–4 days before vaginal opening, which was positively related to steroid levels, GAL, fat intake and body fat accrual after puberty. These findings suggest that, in addition to providing a signal for puberty onset, early fat ingestion acting through mechanisms involving the steroids and orexigenic peptides may be related to long‐term patterns of eating and body weight regulation.
A new tropiduchid planthopper genus and species from China with descriptions of in copula genitalic structures (Hemiptera: Fulgoromorpha)
Authors: WANG RONG‐RONG , LIANG AI‐PING , WEBB MICHAEL D.
Published: March 2009

Abstract The new planthopper taxon, Garumnella bella gen.n., sp.n., from Xizang, China, is described and illustrated, including external morphology of adult and eggs and structures of the male and female genitalia. The new genus is compared with Garumna Melichar and Paragarumna Muir, resulting in Paragarumna (syn.n.) being placed as a junior synonym of Garumna, with two new combinations, i.e. Garumna pseudolepida (Muir) comb.n. and Garumna melichari Baker comb.rev. New locality records for Garumna species are given. The morphology of the genitalia and egg of a copulating pair of the new genus is investigated. The female has a ventrally sclerotized posterior vagina forming a torsion groove, an unusual long membranous anterior vagina and an enlarged common oviduct. During copulation both the aedeagus and the torsion groove appear tightly interlocked, which may help to maintain the copulatory position. The aedeagus is observed in the bursa copulatrix.
Performance of three automated fourth‐generation combined HIV antigen/antibody assays in large‐scale screening of blood donors and clinical samples
Authors: Malm K. , Von Sydow M. , Andersson S.
Published: March 2009

summary Since the introduction in the mid‐1980s, HIV testing has gradually improved both in terms of sensitivity and specificity. The so‐called fourth generation of tests, combined HIV antigen/antibody assays, has now been introduced. This study compares three automated combined assays with older third‐generation antibody assays in large‐scale screening. Serum samples from routine screening of blood and plasma donors and clinical samples were investigated for specificity evaluation. Three fourth‐generation combination assays from one manufacturer were compared with three older third‐generation antibody assays from the same manufacturer. More than 40 000 samples per assay were included. For sensitivity, selected panels of confirmed HIV‐1‐ and HIV‐2‐positive samples as well as seroconversion samples (HIV‐1) from commercial panels and also from patients who appeared during the evaluation were used. The specificities of the fourth‐generation tests were 99·91% (AxSYM), 99·95% (ARCHITECT) and 99·97% (PRISM) after repeated testing. Some specificity variation between reagent batches was observed. All HIV‐1‐positive samples were reactive by the three fourth‐generation systems. HIV‐1 seroconversion samples and panels were reactive earlier than by antibody‐only tests. As for HIV‐2 samples, AxSYM failed to detect one (n = 40), whereas PRISM and ARCHITECT detected all (n = 16 for PRISM and n = 52 for ARCHITECT). The new HIV antigen/antibody combination assay systems were found to have high sensitivity and specificity. The instruments provided a rational and easy way of testing at large scale.
Respiratory complications after haematopoietic stem cell transplantation in a patient with chronic granulomatous disease
Authors: Hara K. , Kajiume T. , Kondo T. , Sera Y. , Kawaguchi H. , Kobayashi M.
Published: March 2009

summary Chronic granulomatous disease (CGD) is an inherited immunodeficiency disorder caused by defects in NADPH oxidase and characterized by recurrent life‐threatening bacterial and fungal infections. Although CGD has been considered to be a target for gene therapy, bone marrow transplantation (BMT) is now selected as the radical treatment in most cases. We performed BMT in a patient with CGD with severe infections and experienced respiratory complications of diffuse alveolar haemorrhage and/or infection‐associated alveolar haemorrhage. We suggest that attention be paid to signs of onset of alveolar haemorrhage during BMT in CGD patients.
Early discharge following hip arthroplasty: patients’ acceptance masks doubts and concerns
Authors: Hunt Gillian R. , Hall George M. , Murthy Burra V.S. , O’Brien Seamus , Beverland David , Lynch Martin C. , Salmon Peter
Published: March 2009

Objective  To describe patients’ experience of accelerated discharge after hip arthroplasty in order to test the acceptability to patients of economically driven shortening of post‐operative stay.

Methods  Patients (n = 35) who had received primary total hip replacement up to 12 weeks previously were recruited from two UK orthopaedic units, one of which has pioneered short post‐operative stay (3–4 days), and another one of which retains a traditional regimen of discharge after 6–7 days. Patients were interviewed about their experience of care, focusing particularly on their views related to length of stay and with particular attention to patients’ well‐known tendency to mask critical views of their care. Transcripts were analysed thematically to identify the ways that patients evaluated their care and whether these differed between sites.

Results  Patients were primarily concerned with how attentive and informative hospital staff had been and did not refer to length of stay spontaneously. When prompted about this, they did not question their discharge time, although those in the more traditional unit could not countenance more rapid discharge. Patients in the unit with accelerated discharge described concerns about the consequences of early discharge for them or their family, particularly managing pain and mobility problems at home and needing more support.

Conclusions  Patients’ traditional beliefs about the necessity of prolonged convalescence are not a barrier to early discharge after hip arthroplasty. Nevertheless, some patients’ acceptance of early discharge masks doubts and concerns. More intensive post‐operative management may be needed if clinical care is not to suffer.
Israeli lay persons’ views on priority‐setting criteria for Alzheimer’s disease
Authors: Werner Perla
Published: March 2009

Aim  The aim of this study was to assess Israeli lay persons’ preferences for setting priorities for the care of Alzheimer’s disease (AD).

Background  As the knowledge about AD accumulates, and especially as more therapeutic and non‐therapeutic interventions for its early diagnosis and treatment are developed, health‐care costs associated with the disease rise dramatically. Therefore, setting priorities for funding these therapies, as well as other costs associated with AD is becoming an increasingly complex need.

Methods  A convenience sample of 624 community‐dwelling men and women participated in the study (mean age = 49, range = 20–90). Participants were asked how strongly they agreed or disagreed with 18 criteria that would be used to set priorities for the allocation of resources in the area of AD.

Results  High‐weight criteria included being a life‐threatening condition and the benefit of treatment. Average‐weight criteria included the severity of the disease, treatment costs and equity of access. The age of the patient also was highly rated. All other patient‐related criteria were rated as low. Value orientations and education were the main variables associated with participants’ preferences.

Conclusions  The lay public seems to endorse a multi‐criteria decision process for the allocation of resources in the area of AD. Similar to other diseases – disease‐related criteria were highly preferred. These preferences should be compared with those of other stakeholders such as clinicians and policy makers.
Recurrent wheezing after respiratory syncytial virus or non‐respiratory syncytial virus bronchiolitis in infancy: a 3‐year follow‐up
Authors: Valkonen H. , Waris M. , Ruohola A. , Ruuskanen O. , Heikkinen T.
Published: March 2009

Background:  Recent studies have suggested that rhinovirus‐associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non‐RSV bronchiolitis.

Methods:  We identified retrospectively all children <2 years of age who were admitted to Turku University Hospital because of bronchiolitis in the months of August–December during 1988–2001. The primary outcome was recurrent wheezing that required long‐term asthma medication. Data on asthma medications of the individual children were derived from the Social Insurance Institution of Finland.

Results:  Within the first year after hospitalization, 36 of 217 (16.6%) children with non‐RSV bronchiolitis developed recurrent wheezing, compared with five of 199 (2.5%) children with RSV bronchiolitis [relative risk (RR) 6.6; 95% confidence interval (CI) 2.6–16.5]. The rates of recurrent wheezing were significantly increased in the non‐RSV group also within 2 years (RR 2.9; 95% CI 1.7–5.1) and 3 years (RR 3.4; 95% CI 2.0–5.7) after hospitalization. The increased risk of recurrent wheezing in children with non‐RSV‐associated bronchiolitis was observed both in boys and girls at all time points of the 3‐year follow‐up, and it was not explained by the age difference between the RSV and non‐RSV groups or any confounding seasonal factors.

Conclusion:  Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3‐year follow‐up period than do children with RSV‐induced bronchiolitis.
Mite serine protease activates protease‐activated receptor‐2 and induces cytokine release in human keratinocytes
Authors: Kato T. , Takai T. , Fujimura T. , Matsuoka H. , Ogawa T. , Murayama K. , Ishii A. , Ikeda S. , Okumura K. , Ogawa H.
Published: March 2009

Background:  House dust mites produce serine and cysteine proteases. Mite‐derived proteases have been suggested to be involved in the pathogenesis of allergies; however, whether mite‐derived serine protease activity can stimulate keratinocytes remains unknown.

Methods:  We examined the activation of primary human keratinocytes by serine protease‐rich extract of whole mite culture and compared with that by recombinant group 1 allergens (rDer f 1 and rDer p 1), which exclusively exhibit cysteine protease activity.

Results:  Protease activity of whole mite culture extract (WCE), rDer f 1 and rDer p 1 induced the release of IL‐8 and granulocyte‐macrophage colony‐stimulating factor. Protease activity of WCEs induced a significant upregulation of their mRNA expression but rDer f 1 had much less effect. Protease activity of the WCE stimulated intracellular Ca2+ mobilization but rDer f 1 and rDer p 1 did not. The mobilization induced by agonists for the human protease‐activated receptor (PAR)‐2, an agonist peptide or trypsin, was diminished by pre‐incubation of keratinocytes with WCE. rDer f 1 inefficiently cleaved a synthetic N‐terminal peptide of PAR‐2 at different sites from trypsin, but the resultant peptides did not stimulate the release of interleukin‐8.

Conclusions:  The results suggest that mite‐derived serine protease activity may contribute to the pathogenesis of atopic dermatitis by activating keratinocytes via PAR‐2 activation but cysteine protease activity of Der f 1 and Der p 1 acts via another mechanism.
Molecular and immunological characterization of Asp f 34, a novel major cell wall allergen of Aspergillus fumigatus
Authors: Glaser A. G. , Kirsch A. I. , Zeller S. , Menz G. , Rhyner C. , Crameri R.
Published: March 2009

Background:  Although fungal spores have been recognized as triggers of respiratory allergy and asthma, only two allergenic fungal cell wall components have so far been described.

Methods:  Eighty‐one sequences derived from an Aspergillus fumigatus cDNA library encoding putative allergens were examined for the presence of cell wall components. A new allergen (Asp f 34) was evaluated by Western blots, enzyme‐linked immunosorbent assay (ELISA), peripheral blood mononuclear cell (PBMC) proliferation assays, and skin prick test (SPT).

Results:  The cDNA encoding Asp f 34 contained an open reading frame predicting a protein of 185 amino acids with a molecular weight of 19.38 kDa, showing sequence homology to phiA, an essential protein for the formation of conidia in the genus Aspergillus. The recombinant Asp f 34 was binding IgE from sensitized individuals in Western blots. An ELISA survey showed that 94% of the ABPA and 46% of the A. fumigatus‐sensitized individuals tested had Asp f 34‐specific serum IgE. Asp f 34 induced allergen‐specific proliferation exclusively of PBMCs from patients sensitized to the allergen. Eight patients with anti‐Asp f 34 serum IgE tested reacted positively in SPT, whereas four A. fumigatus‐sensitized individuals without Asp f 34‐specific IgE and eight healthy controls scored negatively.

Conclusions:  A cell wall protein of the phialides of A. fumigatus was identified as a major allergen. Asp f 34 belongs to the Aspergillus‐specific proteins of the phiA family and has relevant potential for a specific diagnosis of Aspergillus sensitization.
Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north‐east Italian population sample
Authors: Mostacciuolo ML , Pastorello E , Vazza G , Miorin M , Angelini C , Tomelleri G , Galluzzi G , Trevisan CP
Published: March 2009

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with a partial deletion on chromosome 4q35. Few relevant investigations have been reported on its epidemiology and were essentially based on clinical diagnosis, having been performed before recognition of the molecular mutation. We report an epidemiological survey on FSHD patients, in which the diagnosis was obtained by combined clinical and molecular evaluation. The survey concerned the north‐east Italian province of Padova, an area of 871,190 inhabitants (1 January 2004). We identified 40 patients affected by FSHD based on clinical diagnosis. In 33 of them, the EcoRI fragment size in the 4q35 region ranged from 14 to 35 kb. Four other patients belonging to the same family harbored a 38‐kb fragment. In these four cases, the relationship between the borderline deletion with the mild FSHD phenotype was corroborated by additional haplotype reconstruction and segregation analysis. Interestingly, the same mild facial‐sparing clinical pattern was apparent only in one other patient with an EcoRI fragment of 32 kb, suggesting that this unusual FSHD phenotype may be due to very small 4q35 deletions. On the whole, estimating a prevalence rate of 44 × 10−6, our survey confirmed FSHD as one of the most frequent neuromuscular disorders in Western populations.
Omani‐type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3
Authors: Tuysuz B , Mizumoto S , Sugahara K , Çelebi A , Mundlos S , Turkmen S
Published: March 2009

We describe a family with progressive skeletal dysplasia and severe spinal involvement, short stature, premature arthrosis and joint contractures diagnosed as spondyloepiphyseal dysplasia Omani type. Mutation analysis in CHST3, the gene encoding for the chondroitin 6‐O‐sulfotransferase‐1 (C6ST‐1), revealed a homozygous missense mutation (T141M) in exon 3 in all three affected members of the family. Using recombinant C6ST‐1, we showed that the identified missense mutation results in a reduction of C6ST‐1 activity to 24–29% of the wild type protein. In addition to the previously noted skeletal features, affected members of this family also had cardiac involvement including mitral, tricuspid and/or aortic regurgitations and type E brachydactyly.
Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case–control study on 171 patients. The EFESO‐children Multicenter Trial
Authors: Acquistapace Franca , Agostinis Fabio , Castella Vincenzo , Kantar Ahmad , Novembre Elio , Perrone Maria Rosaria , Pietrasanta Michele , Sambugaro Renato , Milani Massimo
Published: March 2009

Sublingual‐specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in ‘real life’ in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case–control study to evaluate the effect of SLIT in children (age 6–18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case–control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone® ALK‐Abellò). Controls (n = 81) were defined as sex‐age‐ and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean ± SD) was 4.5 ± 2.5 in cases and 9.0 ± 3.0 in controls (−50%) (p = 0.0001). MS (mean ± SD) was 2.5 ± 1.9 and 3.6 ± 2.1 in the case and control groups, respectively (−31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2‐yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.
Why colour in subterranean vertebrates? Exploring the evolution of colour patterns in caecilian amphibians
Authors: WOLLENBERG K. C. , JOHN MEASEY G.
Published: March 2009

The proximate functions of animal skin colour are difficult to assign as they can result from natural selection, sexual selection or neutral evolution under genetic drift. Most often colour patterns are thought to signal visual stimuli; so, their presence in subterranean taxa is perplexing. We evaluate the adaptive nature of colour patterns in nearly a third of all known species of caecilians, an order of amphibians most of which live in tropical soils and leaf litter. We found that certain colour pattern elements in caecilians can be explained based on characteristics concerning above‐ground movement. Our study implies that certain caecilian colour patterns have convergently evolved under selection and we hypothesize their function most likely to be a synergy of aposematism and crypsis, related to periods when individuals move overground. In a wider context, our results suggest that very little exposure to daylight is required to evolve and maintain a varied array of colour patterns in animal skin.
Tracking blood products in blood centres using radio frequency identification: a comprehensive assessment
Authors: Davis Rodeina , Geiger Bradley , Gutierrez Alfonso , Heaser Julie , Veeramani Dharmaraj
Published: March 2009

Background and Objectives  Radio frequency identification (RFID) can be a key enabler for enhancing productivity and safety of the blood product supply chain. This article describes a systematic approach developed by the RFID Blood Consortium for a comprehensive feasibility and impact assessment of RFID application in blood centre operations.

Materials and Methods  Our comprehensive assessment approach incorporates process‐orientated and technological perspectives as well as impact analysis. Assessment of RFID‐enabled process redesign is based on generic core processes derived from the three participating blood centres. The technological assessment includes RFID tag readability and performance evaluation, testing of temperature and biological effects of RF energy on blood products, and RFID system architecture design and standards. The scope of this article is limited to blood centre processes (from donation to manufacturing/distribution) for selected mainstream blood products (red blood cells and platelets).

Results  Radio frequency identification can help overcome a number of common challenges and process inefficiencies associated with identification and tracking of blood products. High frequency‐based RFID technology performs adequately and safely for red blood cell and platelet products. Productivity and quality improvements in RFID‐enabled blood centre processes can recoup investment cost in a 4‐year payback period.

Conclusion  Radio frequency identification application has significant process‐orientated and technological implications. It is feasible and economically justifiable to incorporate RFID into blood centre processes.
The unknown genocide: How one country's culture is destroying the girl child
Authors: Sumner Molly M
Published: March 2009

Female feticide and infanticide is occurring at an alarming rate in India as a result of preference for sons. The cultural reasons for sex‐selective abortions and the government's current strategies against this problem are identified. However, the problem's scope might be too great for the Indian government. Humanitarian efforts are needed to save the girl child. Nurses are a key group of people that need to be made aware of this issue as they are advocates for vulnerable populations.
Effect of breast‐feeding on pain relief during infant immunization injections
Authors: Abdel Razek Aida , AZ El‐Dein Nagwa
Published: March 2009

Using a quasi‐experimental design, this study was conducted in two maternal & child health centres in Jordan to examine the effects of breast‐feeding on pain relief during neonatal immunization injections. Inclusion criteria were first year of age, breast‐fed and no concurrent illness. Infants were divided into two groups (of 60 infants for each). One is intervention group: mothers were taken to a private room, seated and reclined on a comfortable chair with their infants awake in their arms, without cloth and with clean diapers. The mothers cradled their infants during breast‐feeding to maintain full‐body skin‐to‐skin contact during immunization injections. The other is control group: infants were observed during routine immunization in maternal & child health centres. Pain responses of infants during and after immunization were assessed by using Facial Pain Rating Scale and Neonatal/Infant Pain Scale (NIPS), before, during and after the procedure. Infants' heart rates and duration of crying for both groups were calculated. Findings revealed that the crying time was shorter in intervention (breast‐fed) group than in the control group with a statistically significant difference in the duration of crying during and after immunization. We concluded that, breast‐feeding and skin‐to‐skin contact significantly reduced crying in infants receiving immunization.
Nursing considerations for dual diagnosis in mental health
Authors: Edward Karen‐Leigh , Munro Ian
Published: March 2009

It is the intention of this literature review to present suggestions for nursing practice with reference to the care of the dually diagnosed. Nursing care of the dually diagnosed client is complex. Clinicians from both drug and alcohol services and mental health services have long recognized that neither service area provides adequate clinical care to those clients who have a dual diagnosis of substance abuse and mental illness. It is now > 10 years since a ground‐breaking Australian study recognized this. To ascertain whether there has been improvement in the service management of clients who have a dual diagnosis, and to determine the best practice interventions in the area of mental health nursing, we undertook a review of the literature. The databases CINAHL, MEDLINE, PsycARTICLES and PsychINFO were searched and 185 articles met the inclusion criteria. From this review, it seems that gaps still remain in the provision of services and that mental health nurses might be best placed to provide integrated care to those clients who have a dual diagnosis and present to mental health services. This requires mental health nurses to have skills in substance use detection and knowledge of potential care implications for the client in the context of their substance use.
Improving nurses' therapeutic attitude to patients who use illicit drugs: Workplace drug and alcohol education is not enough
Authors: Ford Rosemary , Bammer Gabriele , Becker Niels
Published: March 2009

This study examines the impact of workplace drug and alcohol education on nurses' therapeutic attitude to patients who use illicit drugs. It builds on a study of the generalist nursing workforce in the Australian Capital Territory in 2003, which showed that the interaction of role support with workplace drug and alcohol education facilitated nurses' therapeutic attitude. This paper explores this interaction in detail, showing that workplace education has no independent association with therapeutic attitude and that an effect from education only occurs when nurses have at least a moderate level of role support. Nursing workforce development needs to focus on strategies that provide role support for nurses as they work with this clinically challenging patient group. Without the ready availability of someone in the nurse's clinical field to advise and assist them, efforts to increase nurses' knowledge and skills are wasted