bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear and membrane expression of the angiogenesis regulator delta‐like ligand 4 (DLL4) in normal and malignant human tissues
Authors: Martinez Juan Carlos , Müller Marcus M , Turley Helen , Steers Graham , Choteau Ludovine , Li Ji‐Liang , Sainson Richard , Harris Adrian L , Pezzella Francesco , Gatter Kevin C
Published: April 2009

Aims:  Delta‐like ligand 4 (DLL4) is one of five known Notch ligands in mammals and interacts predominantly with Notch 1. DLL4 is induced by vascular endothelial growth factor (VEGF) and acts downstream of VEGF as a ‘brake’ on VEGF‐induced vessel growth, forming an autoregulatory negative feedback loop inactivating VEGF. This action was believed to occur only in vascular development, raising hopes that DLL4 could be a specific drug target for controlling vessel growth in tumours and other pathological conditions. Our aim was to pursue this by raising a monoclonal antibody to the internal domain of DLL4 and assess its distribution in normal and malignant tissues in comparison with antibodies against the external domain of DLL4.

Methods and results:  The anti‐DLL4 monoclonal antibody was raised using conventional mouse hybridoma techniques. The antibody has been fully characterized by Western blotting and transfectant immunostaining. It has also been comprehensively compared with other antibodies against both the internal and external domains of DLL4. The antigen is widely expressed on human tissues not only on endothelium but also on epithelium and stromal cells. Indeed, in our comprehensive survey only pulmonary alveoli failed to express DLL4. Of a wide range of malignancies, most also expressed DLL4 on tumour cells with a predominantly cytoplasmic pattern, although a number also displayed nuclear positivity.

Conclusions:  Contrary to previous beliefs, DLL4 is widely distributed in tissues other than vessels including many malignancies. Furthermore, the molecule is internalized on binding its receptor and often transported to the nucleus. These findings raise many interesting possibilities for further study of DLL4 and its potential as a therapeutic target.
Improvement of the antimicrobial activity of edible mushroom extracts by inhibition of oxidative enzymes
Authors: Santoyo Susana , Ramírez‐Anguiano Ana Cristina , Reglero Guillermo , Soler‐Rivas Cristina
Published: April 2009

The antimicrobial properties of water and methanol extracts from edible mushroom species were evaluated against Escherichia coli, Staphylococcus aureus and Candida albicans. Only water extracts from Lentinus edodes, Boletus edulis and Pleurotus ostreatus showed antimicrobial activity against all tested microorganisms. Their methanol extracts showed antimicrobial activity too but to a lower extent than the water extracts. Moreover, methanol extracts from Cantharellus cibarius and Lactarius deliciosus, showed also a slight activity against S. aureus. However, the antimicrobial properties of the mushroom water extracts might have been always underestimated considering that when oxidative enzymes inhibitors were added before the experimental assay, the water extracts from C. cibarius, L. deliciosus, Agaricus bisporus and Amanita cesarea showed important antimicrobial activity and the water extracts of B. edulis and P. ostreatus increased their activity. These enzymes might degrade potential antimicrobial compounds during the extraction procedure or interfere with their activity.
Perspectives on professional values among nurses in Taiwan
Authors: Shih Fu‐Jin , Lin Yaw‐Sheng , Smith Marlaine C , Liou Yiing‐Mei , Chiang Hsien‐Hsien , Lee Szu‐Hsien , Gau Meei‐Ling
Published: April 2009

Aim.  The purpose of this study was to identify the most important contemporary professional nursing values for nursing clinicians and educators in Taiwan.

Background.  Nursing values are constructed by members of political and social systems, including professional nursing organisations and educational institutions. Nurses’ personal value systems shape the development of these professional values. An understanding of nurses’ perceptions of professional values will enable the profession to examine consistencies with those reflected in existing and emerging educational and practice environments.

Design.  A qualitative descriptive study was conducted using the focus‐group discussion method.

Methods.  A purposive sample of 300 registered nurses in Taiwan, consisting of 270 nursing clinicians and 30 faculty members, participated in 22 focus‐group interviews. Data were analysed using a systematic process of content analysis.

Results.  Six prominent values related to professional nursing were identified: (a) caring for clients with a humanistic spirit; (b) providing professionally competent and holistic care; (c) fostering growth and discovering the meaning of life; (d) experiencing the ‘give‐and‐take’ of caring for others; (e) receiving fair compensation; and (f) raising the public’s awareness of health promotion. Four background contexts framed the way participants viewed the appropriation of these values: (a) appraising nursing values through multiple perspectives; (b) acquiring nursing values through self‐realisation; (c) recognising nursing values through professional competency and humanistic concerns and (d) fulfilling nursing values through coexisting self‐actualisation. A conceptual framework was developed to represent this phenomenon.

Conclusion.  The most important professional nursing values according to the perspectives of nurses in Taiwan were identified. These values reflect benefits to society, to nurses themselves and to the interdisciplinary team.

Relevance to clinical practice.  Nurses’ awareness of their own values and of how these values influence their behaviour is an essential component of humanistic nursing care. Nursing educators need to develop better strategies for reflection and integration of both personal and professional philosophies and values.
A new method for estimating effective population sizes from a single sample of multilocus genotypes
Authors: WANG JINLIANG
Published: April 2009

Equations for the effective size (Ne) of a population were derived in terms of the frequencies of a pair of offspring taken at random from the population being sibs sharing the same one or two parents. Based on these equations, a novel method (called sibship assignment method) was proposed to infer Ne from the sibship frequencies estimated from a sibship assignment analysis, using the multilocus genotypes of a sample of offspring taken at random from a single cohort in a population. Comparative analyses of extensive simulated data and some empirical data clearly demonstrated that the sibship assignment method is much more accurate [measured by the root mean squared error, RMSE, of 1/(2Ne)] than other methods such as the heterozygote excess method, the linkage disequilibrium method, and the temporal method. The RMSE of 1/(2Ne) from the sibship assignment method is typically a small fraction of that from other methods. The new method is also more general and flexible than other methods. It can be applied to populations with nonoverlapping generations of both diploid and haplodiploid species under random or nonrandom mating, using either codominant or dominant markers. It can also be applied to the estimation of Ne for a subpopulation with immigration. With some modification, it could be applied to monoecious diploid populations with self‐fertilization, and to populations with overlapping generations.
BcsQ is an essential component of the Escherichia coli cellulose biosynthesis apparatus that localizes at the bacterial cell pole
Authors: Le Quéré Benjamin , Ghigo Jean‐Marc
Published: April 2009

Biofilms are microbial communities characterized by three‐dimensional growth resulting from the ability of individual cells to adhere to each other as well as to produce an extracellular matrix that ensures biofilm physical cohesion. Numerous bacteria produce cellulose as a biofilm matrix polymer, a property relying on the expression of bacterial cellulose synthesis (Bcs) proteins and their post‐translational activation upon binding of cyclic di‐guanosine mono‐phosphate second messenger (c‐di‐GMP) produced by diguanylate cyclases. In Escherichia coli and other Enterobacteriaceae, two genes of unknown function, yhjR and yhjQ, are located upstream of the bcs genes. Here, we show that yhjQ, but not yhjR, is essential for cellulose biosynthesis; it has therefore been renamed bcsQ. Using a green fluorescent protein (GFP) fusion approach, we demonstrate that BcsQ, a MinD homologue, displays a polar localization and that cell‐to‐cell adhesion is initiated through production of cellulose at the BcsQ‐labelled pole. Although we did not detect a similar localization for other Bcs proteins, immunogold labelling of cellulose itself at the pole of individual bacteria indicates the localized activity of the cellulose biosynthesis apparatus. These results therefore suggest that BcsQ could participate in spatial restriction of cellulose biosynthesis activity in Enterobacteriaceae.
A conserved small RNA promotes silencing of the outer membrane protein YbfM
Authors: Rasmussen Anders Aamann , Johansen Jesper , Nielsen Jesper S. , Overgaard Martin , Kallipolitis Birgitte , Valentin‐Hansen Poul
Published: April 2009

In the past few years an increasing number of small non‐coding RNAs (sRNAs) in enterobacteria have been found to negatively regulate the expression of outer membrane proteins (OMPs) at the post‐transcriptional level. These RNAs act under various growth and stress conditions, suggesting that one important physiological role of regulatory RNA molecules in Gram‐negative bacteria is to modulate the cell surface and/or to prevent accumulation of OMPs in the envelope. Here, we extend the OMP–sRNA network by showing that the expression of the OMP YbfM is silenced by a conserved sRNA, designated MicM (also known as RybC/SroB). The regulation is strictly dependent on the RNA chaperone Hfq, and mutational analysis indicates that MicM sequesters the ribosome binding site of ybfM mRNA by an antisense mechanism. Furthermore, we provide evidence that Hfq strongly enhances the on‐rate of duplex formation between MicM and its target RNA in vitro, supporting the idea that a major cellular role of the RNA chaperone is to act as a catalyst in RNA–RNA duplex formation.
Influence of Tumour Condition on the Macrophage Activity in Candida albicans Infection
Authors: Venturini J. , De Camargo M. R. , Félix M. C. , Vilani‐Moreno F. R. , De Arruda M. S. P.
Published: April 2009

To better understand the interactions between opportunistic fungi and their hosts, we investigated hydrogen peroxide (H2O2), nitric oxide and TNF‐α production by peritoneal macrophages from Ehrlich tumour‐bearing mice (TBM) during microbial infections. For this purpose, TBM at days 7, 14 and 21 of tumour progression were inoculated intraperitoneally with C. albicans and evaluated after 24 and 72 h. We observed that TBM showed significant increases in H2O2, TNF‐α levels and fungal clearance at day 7 after C. albicans infection. However, as the tumour advanced, there was a progressive decline in the release of H2O2 and TNF‐α that was paired with the dissemination of C. albicans. These results demonstrate that protective macrophage activities against Candida albicans are limited to the initial stages of tumour growth; continued solid tumour growth weakened the macrophage response and as a consequence, weakened the host’s susceptibility to opportunistic infections.
Association between Asymmetric Dimethylarginine and Neopterin in Patients with and without Angiographic Coronary Artery Disease
Authors: Murr C. , Meinitzer A. , Grammer T. , Schroecksnadel K. , Böhm B. O. , März W. , Fuchs D.
Published: April 2009

The increase of circulating asymmetric dimethylarginine (ADMA) concentrations, a competitive inhibitor of the nitric oxide synthases, is associated with an increased cardiovascular risk and is considered to play a role in endothelial dysfunction. Recently, ADMA production was observed in stimulated human peripheral mononuclear cells. In this study, we examined a potential relationship between concentrations of ADMA and of the immune activation marker neopterin in patients scheduled for coronary angiography. In a cross‐sectional approach, blood concentrations of ADMA, homocysteine, neopterin, folic acid and vitamins B6 and B12 were compared in 2030 patients, which were recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. ADMA concentrations did not differ between patients with coronary artery disease (CAD) (mean ± SD: 0.82 ± 0.15 μmol/l) and controls (0.81 ± 0.14 μmol/l; Welch’s t‐test: P = n.s.). ADMA concentrations correlated with homocysteine (rs = 0.207) and vitamin B6 (rs = −0.190), and an even stronger correlation with neopterin (rs = 0.276; all P < 0.0001) was observed. In conclusion, increased ADMA concentrations in patients at risk for atherosclerosis are associated with increased neopterin concentrations. Data suggest that immune activation may contribute to increased ADMA production in CAD patients.
Weed management challenges in small‐holder potato systems in Bhutan
Authors: RODER W , DOCHEN T , NIDUP K , DORJI S
Published: April 2009

Over the past four decades potato has emerged as the most important cash crop for Bhutanese mountain farmers. Farmers’ feedback and field observations were used to describe weed populations, weed management and weed‐production environment‐yield interactions in small‐holder potato production systems. Weed species across a range of locations in order of declining importance are: Persicaria runcinata, Galium aparine, Fagopyrum dibotrys, Digitaria ciliaris, Commelina maculata, Galinsoga parviflora and Persicaria nepalensis. The same species were common in the traditional buckwheat and maize production systems as well as the more recently established potato production systems. Limited associations between soil properties, management practices, weed species abundance and potato yield were observed. Species emerging as potential problem weeds, especially P. runcinata and F. dibotrys, are little known outside the Himalayan region. The increase in P. runcinata, reported by 42% of the respondents, was attributed to the use of metribuzin, cutting of rhizomes by plough or spade, high inputs of fertiliser and continuous cultivation of potato by 61%, 17%, 9%, 9% and 4% of respondents respectively. Metribuzin application reduced growth of P. runcinata but could not fully control it. Metribuzin is an effective and affordable weed management tool for small‐holder potato farmers, but perennial weed species need further research, combining mechanical and chemical methods with cropping strategies.
TNF, LTA and TGFB1 genotype distributions among acute graft‐vs‐host disease subsets after HLA‐matched unrelated hematopoietic stem cell transplantation: a pilot study
Authors: Shah R. , Selby S. T. , Yokley B. , Slack R. S. , Hurley C. K. , Posch P. E.
Published: April 2009

Cytokine single nucleotide polymorphisms and consequent production levels have been associated with acute graft‐vs‐host disease (aGVHD) development. The aim of this pilot study was to determine whether polymorphisms in tumor necrosis factor (TNF), lymphotoxin alpha (LTA) and transforming growth factor beta 1 (TGFB1) showed any association with aGVHD severity. Novel alleles and polymorphisms were identified for each cytokine locus. Genotype distributions were examined in 38 recipient–donor pairs (all chronic myelogenous leukemia in the first chronic phase) with either low‐grade (grades 0–I) or high‐grade (grades III–IV) aGVHD. Although no significant differences were found, some trends were noted in genotype distributions among aGVHD‐grade groups. Power calculations determined that substantially more pairs would be required to show significant associations in distributions among aGVHD‐grade groups.
Asthma and rhinoconjunctivitis comorbidity: United airway disease or inherited target organs?
Authors: Garcia‐Marcos Luis , Rubi Ruiz Teresa , Garcia‐Hernandez Gloria , Suarez‐Varela Maria Morales , Valverde‐Molina Jose , Sanchez‐Solis Manuel
Published: April 2009

Garcia‐Marcos L, Ruiz TR, Garcia‐Hernandez G, Suarez‐Varela MM, Valverde‐Molina J, Sanchez‐Solis M. Asthma and rhinoconjunctivitis comorbidity: United airway disease or inherited target organs? Pediatr Allergy Immunol 2010: 21: e142–e148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard

The idea of a united airway disease for asthma and rhinoconjunctivitis is supported by clinical and epidemiological data. However, many asthmatics do not have rhinoconjunctivitis and vice versa. The aim of this study was to investigate if the family history of a specific organ involvement is associated with the implication of the same organ in the allergic child. According to the organ involvement in either or both parents, the family history of 739 children who were skin prick positive to either Dermatophagoides pteronyssinus or D. farinae or both was defined as: asthma and rhinoconjunctivitis positive; asthma and rhinoconjunctivitis negative; asthma negative and rhinoconjunctivitis positive; and asthma positive and rhinoconjunctivitis negative. Asthma and rhinoconjunctivitis in the children were defined according to the International Study of Asthma and Allergies in Childhood questionnaire. Associations between each type of family history and the presence of asthma and/or rhinoconjunctivitis in the children were calculated and adjusted for usual confounders. Adjusted odds ratio of children having asthma, when family history included asthma, was 2.48 (1.38–4.45) when it also included rhinoconjunctivitis; and 2.13 (1.12–4.05) when it did not. However, family history of rhinoconjunctivitis was not associated with asthma in the child. Conversely, the odds ratio of children having rhinoconjunctivitis when family history included rhinoconjunctivitis was 1.84 (1.05–3.21) when it also included asthma; and 1.89 (1.23–2.89) when it did not. Family history of asthma was not associated with rhinoconjunctivitis in the child. In a population of children sensitized to mites, the organ or organs (nose and/or lung) which are implicated in parents tend to be also involved in their children.
Long‐lasting dysregulation of gene expression in corticostriatal circuits after repeated cocaine treatment in adult rats: effects on zif 268 and homer 1a
Authors: Unal Cagri T. , Beverley Joel A. , Willuhn Ingo , Steiner Heinz
Published: April 2009

Human imaging studies show that psychostimulants such as cocaine produce functional changes in several areas of cortex and striatum. These may reflect neuronal changes related to addiction. We employed gene markers (zif 268 and homer 1a) that offer a high anatomical resolution to map cocaine‐induced changes in 22 cortical areas and 23 functionally related striatal sectors, in order to determine the corticostriatal circuits altered by repeated cocaine exposure (25 mg/kg, 5 days). Effects were investigated 1 day and 21 days after repeated treatment to assess their longevity. Repeated cocaine treatment increased basal expression of zif 268 predominantly in sensorimotor areas of the cortex. This effect endured for 3 weeks in some areas. These changes were accompanied by attenuated gene induction by a cocaine challenge. In the insular cortex, the cocaine challenge produced a decrease in zif 268 expression after the 21‐day, but not 1‐day, withdrawal period. In the striatum, cocaine also affected mostly sensorimotor sectors. Repeated cocaine resulted in blunted inducibility of both zif 268 and homer 1a, changes that were still very robust 3 weeks later. Thus, our findings demonstrate that cocaine produces robust and long‐lasting changes in gene regulation predominantly in sensorimotor corticostriatal circuits. These neuronal changes were associated with behavioral stereotypies, which are thought to reflect dysfunction in sensorimotor corticostriatal circuits. Future studies will have to elucidate the role of such neuronal changes in psychostimulant addiction.
Multiple dimensions in bi‐directional synesthesia
Authors: Gebuis Titia , Nijboer Tanja C. W. , Van der Smagt Maarten J.
Published: April 2009

Grapheme‐color synesthetes report seeing a specific color when a number is perceived. The reverse, the synesthetic experience of a specific grapheme after the percept of a color is extremely rare. However, recent studies have revealed these interactions at both behavioral and neurophysiological levels. We investigated whether similar neuronal processes (i.e. perceptual and/or attentional) may underlie this bi‐directional interaction by measuring event‐related potentials (ERPs) during both a number‐color and color‐number priming task. In addition, we investigated the unitarity of synesthesia by comparing two distinct subtypes of synesthetes, projectors and associators, and assessed whether consistencies between measures (i.e. behavioral and electrophysiological) were present across synesthetes. Our results show longer reaction times for incongruent compared with congruent trials in both tasks. This priming effect is also present in the P3b latency (parietal electrode site) and P3a amplitude (frontal electrode site) of the ERP data. Interestingly, projector and associator synesthetes did not reveal distinct behavioral or electrophysiological patterns. Instead, a dissociation was found when synesthetes were divided in two groups on the basis of their behavioral data. Synesthetes with a large behavioral priming effect revealed ERP modulation at the frontal and parietal electrode sites, whereas synesthetes with a small priming effect revealed a frontal effect only. Together, these results show, for the first time, that similar neural mechanisms underlie bi‐directional synesthesia in synesthetes that do not report a synesthetic experience of a grapheme when a color is perceived. In addition, they add support for the notion of the existence of both ‘lower’ and ‘higher’ synesthetes.
Critical role of insular cortex in taste but not odour aversion memory
Authors: Bertrand Desgranges , Yannick Sevelinges , Mathilde Bonnefond , Frédéric Lévy , Nadine Ravel , Guillaume Ferreira
Published: April 2009

Conditioned odour aversion (COA) and conditioned taste aversion (CTA) result from the association of a novel odour or a novel taste with delayed visceral illness. The insular cortex (IC) is crucial for CTA memory, and the present experiments sought to determine whether the IC is required for the formation and the retrieval of COA memory as it is for CTA. We first demonstrated that ingested odour is as effective as taste for single‐trial aversion learning in rats conditioned in their home cage. COA, like CTA, tolerates long intervals between the ingested stimuli and the illness and is long‐lasting. Transient inactivation of the IC during acquisition spared COA whereas it greatly impaired CTA. Similarly, blockade of protein synthesis in IC did not affect COA but prevented CTA consolidation. Moreover, IC inactivation before retrieval tests did not interfere with COA memory expression when performed either 2 days (recent memory) or 36 days after acquisition (remote memory). Similar IC inactivation impaired the retrieval of either recent or remote CTA memory. Altogether these findings indicate that the IC is not necessary for aversive odour memory whereas it is essential for acquisition, consolidation and retrieval of aversive taste memory. We propose that the chemosensory stimulations modulate IC recruitment during the formation and the retrieval of food aversive memory.
Serotonin excites fast‐spiking interneurons in the striatum
Authors: Blomeley Craig P. , Bracci Enrico
Published: April 2009

Fast‐spiking interneurons (FSIs) control the output of the striatum by mediating feed‐forward GABAergic inhibition of projection neurons. Their neuromodulation can therefore critically affect the operation of the basal ganglia. We studied the effects of 5‐hydroxytryptamine (5‐HT, serotonin), a neurotransmitter released in the striatum by fibres originating in the raphe nuclei, on FSIs recorded with whole‐cell techniques in rat brain slices. Bath application of serotonin (30 μm) elicited slow, reversible depolarizations (9 ± 3 mV) in 37/46 FSIs. Similar effects were observed using conventional whole‐cell and gramicidin perforated‐patch techniques. The serotonin effects persisted in the presence of tetrodotoxin and were mediated by 5‐HT2C receptors, as they were reversed by the 5‐HT2 receptor antagonist ketanserin and by the selective 5‐HT2C receptor antagonist RS 102221. Serotonin‐induced depolarizations were not accompanied by a significant change in FSI input resistance. Serotonin caused the appearance of spontaneous firing in a minority (5/35) of responsive FSIs, whereas it strongly increased FSI excitability in each of the remaining responsive FSIs, significantly decreasing the latency of the first spike evoked by a current step and increasing spike frequency. Voltage‐clamp experiments revealed that serotonin suppressed a current that reversed around −100 mV and displayed a marked inward rectification, a finding that explains the lack of effects of serotonin on input resistance. Consistently, the effects of serotonin were completely occluded by low concentrations of extracellular barium, which selectively blocks Kir2 channels. We concluded that the excitatory effects of serotonin on FSIs were mediated by 5‐HT2C receptors and involved suppression of an inwardly rectifying K+ current.
A mitochondrial genome phylogeny of the Neuropterida (lace‐wings, alderflies and snakeflies) and their relationship to the other holometabolous insect orders
Authors: Cameron Stephen L. , Sullivan Jaron , Song Hojun , Miller Kelly B. , Whiting Michael F.
Published: April 2009

We present a mitochondrial (mt) genome phylogeny inferring relationships within Neuropterida (lacewings, alderflies and camel flies) and between Neuropterida and other holometabolous insect orders. Whole mt genomes were sequenced for Sialis hamata (Megaloptera: Sialidae), Ditaxis latistyla (Neuroptera: Mantispidae), Mongoloraphidia harmandi (Raphidioptera: Raphidiidae), Macrogyrus oblongus (Coleoptera: Gyrinidae), Rhopaea magnicornis (Coleoptera: Scarabaeidae), and Mordella atrata (Coleoptera: Mordellidae) and compared against representatives of other holometabolous orders in phylogenetic analyses. Additionally, we test the sensitivity of phylogenetic inferences to four analytical approaches: inclusion vs. exclusion of RNA genes, manual vs. algorithmic alignments, arbitrary vs. algorithmic approaches to excluding variable gene regions and how each approach interacts with phylogenetic inference methods (parsimony vs. Bayesian inference). Of these factors, phylogenetic inference method had the most influence on interordinal relationships. Bayesian analyses inferred topologies largely congruent with morphologically‐based hypotheses of neuropterid relationships, a monophyletic Neuropterida whose sister group is Coleoptera. In contrast, parsimony analyses failed to support a monophyletic Neuropterida as Raphidioptera was the sister group of the entire Holometabola excluding Hymenoptera, and Neuroptera + Megaloptera is the sister group of Diptera, a relationship which has not previously been proposed based on either molecular or morphological data sets. These differences between analytical methods are due to the high among site rate heterogeneity found in insect mt genomes which is properly modelled by Bayesian methods but results in artifactual relationships under parsimony. Properly analysed, the mt genomic data set presented here is among the first molecular data to support traditional, morphology‐based interpretations of relationships between the three neuropterid orders and their grouping with Coleoptera.
TNF‐α and IL‐10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population
Authors: Javor J , Chmurova N , Parnicka Z , Ferencik S , Grosse‐Wilde H , Buc M , Svecova D
Published: April 2009

Backround  Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood.

Objective  The aim of our case‐control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL‐1α, IL‐1β, IL‐1RI, IL‐1Ra, IL‐4Rα, IL‐12, IFN‐γ, TGF‐β1, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10) are associated with pemphigus vulgaris in the Slovak population.

Methods  DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method.

Results  We found a weak association between pemphigus vulgaris and polymorphic variants in TNF‐α and IL‐10 genes only, with haplotypes TNF‐α–308G/–238G and IL‐10 –1082A/–819C/–592C being significantly overrepresented in pemphigus vulgaris patients (TNF‐α GG: 94.12% vs. 82.86%, P = 0.0216; IL‐10 ACC: 44.12% vs. 30.00%, P = 0.0309).

Conclusions  Our preliminary results suggest that certain TNF‐α and IL‐10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.
A Randomized Controlled Trial of a Specialist Liaison Worker Model for Young People with Intellectual Disabilities with Challenging Behaviour and Mental Health Needs
Authors: Raghavan R. , Newell R. , Waseem F. , Small N.
Published: April 2009

Background  Twenty six young people with intellectual disabilities and mental health needs from Pakistani and Bangladeshi communities were recruited as part of a bigger study to examine the effectiveness of a liaison worker in helping young people and their families access appropriate intellectual disabilities and mental health services.

Method  Twelve young people were randomly allocated to the treatment group, which had the help of the liaison worker, and 14 young people were allocated to the control group without the help of a liaison worker. Baseline measures were undertaken with all the young people and their carers. This was followed by a 9‐month trial, consisting of the liaison worker helping the treatment group to get in touch with and take up appropriate services, mainly in the areas of psychiatric appointments, benefits advice, house adaptations, leisure facilities and support and care for the young person. The control group participants did not have the access to the liaison worker and were accessing services using the normal routine. Assessments were carried out post‐treatment to assess whether the use of a liaison worker had had any effect on outcomes for the two groups.

Results  Twelve young people completed the study in the treatment group and 14 in the control group. Participants allocated to the specialist liaison worker had statistically significantly more frequent contact with services and with more outcomes, than the control group, and significantly lower scores on the Strengths and Difficulties Questionnaire (SDQ).

Conclusion  The use of specialist liaison services in ensuring adequate access to services for young people with learning disabilities and mental health needs from the South Asian community proved to be significant and effective compared with young people and their families accessing services on their own.
The Utility of the Personal Wellbeing Index Intellectual Disability Scale in an Australian Sample
Authors: McGillivray J. A. , Lau A. L. D. , Cummins R. A. , Davey G.
Published: April 2009

Background  Subjective wellbeing (SWB) in people with intellectual disabilities has been the focus of increased interest in the identification of support needs and as an outcome measure for interventions and service delivery evaluations. It is therefore important to conduct further research in this area, and to develop appropriate scales to measure SWB.

Methods  A new scale, the Personal Wellbeing Index‐Intellectual Disability (PWI‐ID) was administered to 114 adults with mild (n = 82) or moderate (n = 32) level ID in Victoria, Australia.

Results  The PWI‐ID demonstrated good reliability and validity. A comparison of the findings with previous research indicates that participants’ SWB levels are within the normative range, and are similar to those reported by the general population.

Conclusions  The results support the notion that individuals with ID do not experience life quality lower than normal, which can be explained theoretically by the Theory of Subjective Wellbeing Homeostasis. The use of the PWI‐ID may ultimately assist in ensuring that the needs of people with ID are being met and inform the planning and delivery of congruent resources and services.
Altered histamine H3receptor radioligand binding in post‐mortem brain samples from subjects with psychiatric diseases
Authors: Jin CY , Anichtchik O , Panula P
Published: April 2009

Background and purpose: Histamine is a modulatory neurotransmitter in the brain. Auto‐ and hetero‐histamine H3receptors are present in human brain and are potential targets of antipsychotics. These receptors may also display disease‐related abnormalities in psychiatric disorders. Here we have assessed how histamine H3receptors in human brain may be affected in schizophrenia, bipolar disorder, major depression.

Experimental approach: Histamine H3receptor radioligand binding assays were applied to frozen post‐mortem prefrontal and temporal cortical sections and anterior hippocampal sections from subjects with schizophrenia, bipolar disorder, major depression and matched controls.

Key results: Compared with the controls, increased H3receptor radioligand binding was found in dorsolateral prefrontal cortex of schizophrenic subjects (especially the ones who were treated with atypical antipsychotics), and bipolar subjects with psychotic symptoms. No differences in H3receptor radioligand binding were found in the temporal cortex. In hippocampal formation of control subjects, H3receptor radioligand binding was prominent in dentate gyrus, subiculum, entorhinal cortex and parasubiculum. Decreased H3binding was found in the CA4 area of bipolar subjects. Decreased H3binding in CA2 and presubiculum of medication‐free bipolar subjects was also seen.

Conclusions and implications: The results suggest that histamine H3receptors in the prefrontal cortex take part in the modulation of cognition, which is impaired in schizophrenic subjects and bipolar subjects with psychotic symptoms. Histamine H3receptors probably regulate connections between hippocampus and various cortical and subcortical regions and could also be involved in the neuropathology of schizophrenia and bipolar disorder.
Advances in histamine pharmacology reveal new drug targets
Authors: Chazot Paul L
Published: April 2009

This Themed Issue consists of three reviews and 11 original articles authored by internationally respected industrial and academic pharmacologists from across three continents. It derives from the highly successful symposium on ‘The H3 and H4 histamine receptors: the antihistamines for the 21st century’, which took place at EPHAR 2008 in Manchester University, and encompasses new roles, new compounds and exciting new therapeutic areas for histamine.
In vitroandin vivocharacterization of A‐940894: a potent histamine H4receptor antagonist with anti‐inflammatory properties
Authors: Strakhova MI , Cuff CA , Manelli AM , Carr TL , Witte DG , Baranowski JL , Vortherms TA , Miller TR , Rundell L , McPherson MJ , Adair RM , Brito AA , Bettencourt BM , Yao BB , Wetter JM , Marsh KC , Liu H , Cowart MD , Brioni JD , Esbenshade TA
Published: April 2009

Background and purpose: The histamine H4receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe thein vitroandin vivoanti‐inflammatory properties of a potent histamine H4receptor antagonist, A‐940894 (4‐piperazin‐1‐yl‐6,7‐dihydro‐5H‐benzo[6,7]cyclohepta[1,2‐d]pyrimidin‐2‐ylamine).

Experimental approach: We have analysed the pharmacological profile of A‐940894 at mouse native, rat recombinant and human recombinant and native, histamine H4receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan‐induced peritonitis.

Key results: A‐940894 potently binds to both human and rat histamine H4receptors and exhibits considerably lower affinity for the human histamine H1, H2or H3receptors. It potently blocked histamine‐evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine‐induced shape change of mouse bone marrow‐derived mast cells and chemotaxis of human eosinophilsin vitro. In a mouse mast cell‐dependent model of zymosan‐induced peritonitis, A‐940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D2levels. Finally, A‐940894 has good pharmacokinetic properties, including half‐life and oral bioavailability in rats and mice.

Conclusions and Implications: These data suggest that A‐940894 is a potent and selective histamine H4receptor antagonist with pharmacokinetic properties suitable for long‐termin vivotesting and could serve as a useful tool for the further characterization of histamine H4receptor pharmacology.
Diagnosis and Management of Asthma in Older Adults
Authors: Chotirmall Sanjay Haresh , Watts Michael , Branagan Peter , Donegan Ciaran F. , Moore Allan , McElvaney Noel Gerard
Published: April 2009

Despite comprehensive guidelines established by the European Global Initiative for Asthma and the U.S. National Asthma Education and Prevention Program on the diagnosis and management of asthma, its mortality in older adults continues to rise. Diagnostic and therapeutic problems contribute to older patients being inadequately treated. The diagnosis of asthma rests on the history and characteristic pulmonary function testing (PFT) with the demonstration of reversible airway obstruction, but there are unique problems in performing this test in older patients and in its interpretation. This review aims to address the difficulties in performing and interpreting PFT in older patients because of the effects of age‐related changes in lung function on respiratory physiology. The concept of “airway remodeling” resulting in “fixed obstructive” PFT and the relevance of atopy in older people with asthma are assessed. There are certain therapeutic issues unique to older patients with asthma, including the increased probability of adverse effects in the setting of multiple comorbidities and issues surrounding effective drug delivery. The use of beta 2‐agonist, anticholinergic, corticosteroid, and anti‐immunoglobulin E treatments are discussed in the context of these therapeutic issues.
Prevalence and Risk Factors of Suspected Elder Abuse Subtypes in People Aged 75 and Older
Authors: Garre‐Olmo Josep , Planas‐Pujol Xènia , López‐Pousa Secundino , Juvinyà Dolors , Vilà Antoni , Vilalta‐Franch Joan ,   on behalf of the Frailty and Dependence in Girona Study Group
Published: April 2009

OBJECTIVES: To assess the prevalence of suspected elder abuse subtypes and to identify related factors.

DESIGN: Cross‐sectional, population‐based, descriptive study.

SETTING: Eight rural villages in Girona, Spain.

PARTICIPANTS: Six hundred seventy‐six inhabitants aged 75 and older.

MEASUREMENTS: All participants were interviewed in their homes using the study protocol, which includes an abuse screen used in previous elder abuse studies and questions about demographic, social, physical, psychiatric, cognitive, and social services variables.

RESULTS: The mean age of the participants was 81.7 ± 4.8; 58.2% were female. Prevalence of suspected neglect abuse was 16.0% (95% confidence interval (CI)=13.2–18.9), prevalence of psychosocial abuse was 15.2% (95% CI=12.8–18.2), prevalence of financial abuse was 4.7% (95% CI=3.0–6.4) and prevalence of physical abuse was 0.1% (95% CI=0.004–0.8). Psychosocial abuse was positively associated with depressive symptoms (odds ratio (OR)=1.65, 95% CI=1.01–2.72), social isolation (OR=0.35, 95% CI=0.18–0.69), and frequent bladder incontinence (OR=2.44, 95% CI=1.23–4.86). Neglect abuse was positively associated with social isolation (OR=0.52, 95% CI=0.27–0.99), use of social services (OR=1.83, 95% CI=1.05–3.20), and living arrangements (OR=5.29, 95% CI=2.65–10.56). Financial abuse was associated with marital status (OR=0.15, 95% CI=0.04–0.59), age 85 and older, (OR=3.84, 95% CI=1.70–8.68), and Mini‐Mental State Examination score (OR=0.85, 95% CI=0.78–0.94).

CONCLUSION: After adjustment for confounding factors, each subtype of suspected elder abuse was associated with different variables. The results of this study suggest that elder abuse cannot be analyzed as a unitary concept and that risk factors must be assessed for each abuse subtype.
Development of a Quantitative Microbial Risk Assessment for Human Salmonellosis Through Household Consumption of Fresh Minced Pork Meat in Belgium
Authors: Bollaerts Kaatje Els , Messens Winy , Delhalle Laurent , Aerts Marc , Van der Stede Yves , Dewulf Jeroen , Quoilin Sophie , Maes Dominiek , Mintiens Koen , Grijspeerdt Koen
Published: April 2009

A quantitative microbial risk assessment (QMRA) according to the Codex Alimentarius Principles is conducted to evaluate the risk of human salmonellosis through household consumption of fresh minced pork meat in Belgium. The quantitative exposure assessment is carried out by building a modular risk model, called the METZOON‐model, which covers the pork production from farm to fork. In the METZOON‐model, the food production pathway is split up in six consecutive modules: (1) primary production, (2) transport and lairage, (3) slaughterhouse, (4) postprocessing, (5) distribution and storage, and (6) preparation and consumption. All the modules are developed to resemble as closely as possible the Belgian situation, making use of the available national data. Several statistical refinements and improved modeling techniques are proposed. The model produces highly realistic results. The baseline predicted number of annual salmonellosis cases is 20,513 (SD9061.45). The risk is estimated higher for the susceptible population (estimate4.713 × 10−5;SD1.466 × 10−5) compared to the normal population(estimate 7.704 × 10−6;SD5.414 × 10−6)and is mainly due to undercooking and to a smaller extent to cross‐contamination in the kitchen via cook's hands.
A retrospective study on the microbiology in patients with oral complaints and oral mucosal lesions
Authors: Dahlén G , Blomquist S , Carlén A
Published: April 2009

Objective:  The aim of this study was to microbiologically analyze oral mucosal samples collected during 2 years from patients with oral mucosal complaints.

Materials and methods:  Mucosal scraping samples were taken from 297 patients and semiquantified by culture for detection of opportunistic microorganisms e.g. Staphylococcus aureus, enterococci, aerobic Gram‐negative bacilli (AGNB) and yeasts. Antibiotic susceptibility test was performed.

Results:  Altogether 297 patients were sampled (mean age 56.8 ± 20.7). Among the 110 patients with known medical condition, 48 were systemically immunocompromised, 35 had systemic diseases, and 27 had only local oral complaints. Opportunists in moderate growth or more were present commonly in all three groups and most frequent in the immunocompromised patients (66.7%). Candida species were the most frequent opportunist (68.8%), however, their level was low and combinations with bacterial opportunists were common (39.6%). All bacterial opportunists tested were antibiotic multiresistant. Follow‐up samples were collected in 23 cases out of which seven showed still presence of opportunists in heavy growth despite repeated treatment with ciprofloxacin.

Conclusions:  This study showed a frequent presence of bacterial and fungal opportunists in patients with oral mucosal complaints, which were most common in immunocompromised individuals, however, also frequent in patients with local oral complaints only. Systematic evaluation of different treatment strategies is needed.
COLOR IN DENTISTRY: MATCH ME, MATCH ME NOT
Authors: Paravina Rade D. , Swift Edward J.
Published: April 2009

This Critical Appraisal focuses on defining color match in dentistry through determination of perceptibility and acceptability visual thresholds. Differences between in vitro and clinical conditions, monochromatic and polychromatic materials, and old and new Commission Internationale de l'Eclairage (International Commission on Illumination; CIE) formulas will be considered. Color difference thresholds can serve as a quality control tool and as guidelines for selection of dental materials and evaluation of their clinical performance.
Identification of Urinary Biomarkers Useful for Distinguishing a Difference in Mechanism of Toxicity in Rat Model of Cholestasis
Authors: Ishihara Kenji , Katsutani Naruo , Asai Naoki , Inomata Akira , Uemura Yuji , Suganuma Akiyoshi , Sawada Kohei , Yokoi Tsuyoshi , Aoki Toyohiko
Published: April 2009

Abstract: This1H nuclear magnetic resonance metabonomics study was aimed to determine urinary biomarkers of cholestasis resulting from inhibition of biliary secretion of bile or obstruction of bile flow. To inhibit biliary secretion of bile, cyclosporine A was administered to male Sprague–Dawley rats. Obstruction of bile flow was induced by administration of 4,4′‐methylene dianiline, α‐naphthylisothiocyanate or bile duct ligation. Clinical pathological and histopathological examinations were performed to confirm cholestatic injury and1H nuclear magnetic resonance spectral data for urine samples were analysed to determine similarities and differences in profiles of metabolites using the Spotfire®. In cyclosporine A‐treated groups, serum total bilirubin and bile acid were significantly increased but no remarkable hepatic histopathological‐changes were observed. In 4,4′‐methylene dianiline‐, α‐naphthylisothiocyanate‐ and bile duct ligation‐treated groups, serum alkaline phosphatase, γ‐glutamyltranspeptidase and total bilirubin levels increased significantly, and hepatic histopathological‐changes were observed. On urinary1H nuclear magnetic resonance spectral analysis, area intensities derived from 0.66 to 1.90 ppm were decreased by cyclosporine A, whereas they were increased by other treatments. These metabolites were identified using the NMR suite®as bile acids, branched‐chain amino acids, n‐butyrate, propionate, methyl malonate and valerate. These metabolites were further investigated by K‐means clustering analysis. The cluster of these metabolites is considered to be altered by cholestasis. We conclude that bile acids, valine and methyl malonate have a possibility to be urinary cholestatic biomarkers, which distinguish a difference in mechanism of toxicity.1H nuclear magnetic resonance metabonomics thus appears to be useful for determining the mechanisms of toxicity and can be front‐loaded in drug safety evaluation and biomarker discovery.