bluuebunny/crossref_metadata_2025 huggingface dataset:
The Terminal Phase of Cytokinesis in theCaenorhabditis elegansEarly Embryo Requires Protein Glycosylation
Authors: Wang Huan , Spang Anne , Sullivan Mark A. , Hryhorenko Jennifer , Hagen Fred K.
Published: June 2005

RNA interference (RNAi) was used to characterize the requirement of protein glycosylation for cell membrane stability during cytokinesis in the early embryo. This screen targeted 13 enzymes or components of polypeptide sugar transferases that initiate either N-glycosylation or three different pathways of O-glycosylation. RNAi of genes in the mucin-type and epidermal growth factor-fringe glycosylation pathways did not affect cytokinesis. However, embryos deficient in N-glycosylation exhibited a variable inability to complete cytokinesis. The most potent block in early embryonic cell division was obtained by RNAi of the polypeptide xylose transferase (ppXyl-T), which is required to initiate the proteoglycan modification pathway. Two generations of ppXyl-T RNAi-feeding treatment reduced the body size, mobility, brood size, and life span of adult animals. Embryos escaping ppXyl-T and Gal-T2 RNAi lethality develop to adulthood but have cytokinesis-deficient offspring, suggesting that glycosyltransferases in the proteoglycan pathway are maternal proteins in the early embryo. Gal-T2::GFP fusions and anti-Gal-T2 antibodies revealed a perinuclear staining pattern, consistent with the localization of the Golgi apparatus. RNAi in green fluorescent protein (GFP)-tagged strains to follow tubulin, PIE-1, and chromatin showed that deficient proteoglycan biosynthesis uncouples the stability of newly formed cell membranes from cytokinesis, whereas cleavage furrow initiation, mitotic spindle function, karyokinesis, and partitioning of intrinsic components are intact.
Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy
Authors: Lee Wing C. , Courtenay Andrew , Troendle Frederick J. , Stallings‐Mann Melody L. , Dickey Chad A. , Delucia Michael W. , Dickson Dennis W. , Eckman Christopher B.
Published: June 2005

Globoid cell leukodystrophy (GLD) or Krabbe disease is a devastating, degenerative neurological disorder caused by mutations in the galactosylceramidase (GALC) gene that severely affect enzyme activity. Currently, treatment options for this disorder are very limited. Enzyme replacement therapy (ERT) has been shown to be effective in lysosomal storage disorders with predominantly peripheral manifestations such as type I Gaucher's and Fabry's disease. Little however is known about the possible benefit of ERT in GLD, which has a substantial central nervous system component. In this study, we examined the effect of peripheral GALC injections in the twitcher mouse model of the disease. Although we were unable to block the precipitous decline that normally occurs just before death, we did observe significant early improvements in motor performance, a substantial attenuation in the initial failure to thrive, and an increase in life span. Immunohistochemical and activity analyses demonstrated GALC uptake in multiple tissues, including the brain. This was associated with a decrease in the abnormal accumulation of the GALC substrate psychosine, which is thought to play a pivotal role in disease pathology. These results indicate that peripheral ERT is likely to be beneficial in GLD.
The Croonian Lecture 2004 Risk: food, fact and fantasy
Authors: Krebs John R
Published: June 2005

We all take risks, but most of the time we do not notice them. We are generally bad at judging the risks we take, and in the end, for some of us, this will prove fatal. Eating, like everything else in life, is not risk free. Is that next mouthful pure pleasure, or will it give you food poisoning? Will it clog your arteries as well as filling your stomach? This lecture weaves together three strands—the public understanding of science, the perception of risk and the role of science in informing government policy—as it explains how food risks are assessed and managed by government and explores the boundaries between the responsibilities of the individual and the regulator. In doing so, it draws upon the science of risk assessment as well as our attitudes to risk in relation to issues such as bovine spongiform encephalopathy, dioxins in salmon and diet and obesity.
Protein–protein interactions as a tool for site‐specific labeling of proteins
Authors: Jäger Marcus , Michalet Xavier , Weiss Shimon
Published: June 2005

Probing structures and dynamics within biomolecules using ensemble and single‐molecule fluorescence resonance energy transfer requires the conjugation of fluorophores to proteins in a site‐specific and thermodynamically nonperturbative fashion. Using single‐molecule fluorescence‐aided molecular sorting and the chymotrypsin inhibitor 2–subtilisin BPN′ complex as an example, we demonstrate that protein–protein interactions can be exploited to afford site‐specific labeling of a recombinant double‐cysteine variant of CI2 without the need for extensive and time‐consuming chromatography. The use of protein–protein interactions for site‐specific labeling of proteins is compatible with and complementary to existing chemistries for selective labeling of N‐terminal cysteines, and could be extended to label multiple positions within a given polypeptide chain.
Oligomerization of the fifth transmembrane domain from the adenosine A2A receptor
Authors: Thévenin Damien , Lazarova Tzvetana , Roberts Matthew F. , Robinson Clifford R.
Published: June 2005

The human adenosine A2A receptor (A2AR) belongs to one of the largest family of membrane proteins, the G‐protein coupled receptors (GPCRs), characterized by seven transmembrane (TM) helices. Little is known about the determinants of their structures, folding, assembly, activation mechanisms, and oligomeric states. Previous studies in our group showed that peptides corresponding to all seven TM domains form stable helical structures in detergent micelles and lipid vesicles. However, the peptides behave differently; TM5 is the only peptide to have a ratio [θ]222/[θ]208 obtained by circular dichroism (CD) spectroscopy>1. This finding suggested to us that TM5 might self‐associate. In the present study, we investigate the unique properties of the TM5 domain. We performed detailed analyses of TM5 peptide behavior in membrane‐mimetic environments using CD spectroscopy, fluorescence spectroscopy and Förster resonance energy transfer, and gel electrophoresis. We find that TM5 peptide has the ability to self‐associate to form oligomeric structures in various hydrophobic milieus and that these oligomers are highly resistant to temperature and chemical denaturation. We also find that mutation of the full‐length A2AR at position M193, which is located in the fifth TM domain, noticeably alters A2AR monomer: dimer ratio as observed on SDS‐PAGE. Our results suggest that parallel association of TM5 dimers may play a role in the known adenosine A2A receptor dimerization. This study represents the first evidence of an individual GPCR transmembrane domain self‐association.
Simultaneous optimization of enzyme activity and quaternary structure by directed evolution
Authors: Vamvaca Katherina , Butz Maren , Walter Kai U. , Taylor Sean V. , Hilvert Donald
Published: June 2005

Natural evolution has produced efficient enzymes of enormous structural diversity. We imitated this natural process in the laboratory to augment the efficiency of an engineered chorismate mutase with low activity and an unusual hexameric topology. By applying two rounds of DNA shuffling and genetic selection, we obtained a 400‐fold more efficient enzyme, containing three non‐active‐site mutations. Detailed biophysical characterization of the evolved variant suggests that it exists predominantly as a trimer in solution, but is otherwise similarly stable as the parent hexamer. The dramatic structural and functional effects achieved by a small number of seemingly innocuous substitutions highlights the utility of directed evolution for modifying protein–protein interactions to produce novel quaternary states with optimized activities.
Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's β‐amyloid peptide
Authors: Christopeit Tony , Hortschansky Peter , Schroeckh Volker , Gührs Karlheinz , Zandomeneghi Giorgia , Fändrich Marcus
Published: June 2005

The formation of polypeptide aggregates represents a nucleated polymerization reaction in which an initial nucleation event (lag phase) is followed by the extension of newly formed nuclei into larger aggregates, including fibrils (growth phase). The efficiencies of these reactions relate to the lag time (lag phase) and to the rate of aggregation (growth phase), which can be determined from experimental aggregation curves. Here we present a mutagenic analysis in which we replace valine 18 of the Alzheimer's Aβ (1–40) peptide with 17 different amino acids and determine its effect on the lag time, and therefore, on the propensity of nucleation. Comparison with various physico‐chemical properties shows that nucleation is affected in a predictable manner depending on the β‐sheet propensity and hydrophobicity of residue 18. In addition, we observe a direct proportionality between the lag time and the rate of aggregation. These data imply that the two reactions, nucleation and polymerization, are governed by very similar physicochemical principles and that they involve the formation of the same types of noncovalent interactions.
Solution structure of thioredoxin h1 from Arabidopsis thaliana
Authors: Peterson Francis C. , Lytle Betsy L. , Sampath Sujatha , Vinarov Dmitriy , Tyler Ejan , Shahan Mark , Markley John L. , Volkman Brian F.
Published: June 2005

Present in virtually every species, thioredoxins catalyze disulfide/dithiol exchange with various substrate proteins. While the human genome contains a single thioredoxin gene, plant thioredoxins are a complex protein family. A total of 19 different thioredoxin genes in six subfamilies has emerged from analysis of the Arabidopsis thaliana genome. Some function specifically in mitochondrial and chloroplast redox signaling processes, but target substrates for a group of eight thioredoxin proteins comprising the h subfamily are largely uncharacterized. In the course of a structural genomics effort directed at the recently completed A. thaliana genome, we determined the structure of thioredoxin h1 (At3g51030.1) in the oxidized state. The structure, defined by 1637 NMR‐derived distance and torsion angle constraints, displays the conserved thioredoxin fold, consisting of a five‐stranded β‐sheet flanked by four helices. Redox‐dependent chemical shift perturbations mapped primarily to the conserved WCGPC active‐site sequence and other nearby residues, but distant regions of the C‐terminal helix were also affected by reduction of the active‐site disulfide. Comparisons of the oxidized A. thaliana thioredoxin h1 structure with an h‐type thioredoxin from poplar in the reduced state revealed structural differences in the C‐terminal helix but no major changes in the active site conformation.
Precursor complex structure of pseudouridine synthase TruB suggests coupling of active site perturbations to an RNA‐sequestering peripheral protein domain
Authors: Hoang Charmaine , Hamilton Christopher S. , G.Mueller Eugene , Ferré‐D'Amaré Adrian R.
Published: June 2005

The pseudouridine synthase TruB is responsible for the universally conserved post‐transcriptional modification of residue 55 of elongator tRNAs. In addition to the active site, the “thumb,” a peripheral domain unique to the TruB family of enzymes, makes extensive interactions with the substrate. To coordinate RNA binding and release with catalysis, the thumb may be able to sense progress of the reaction in the active site. To establish whether there is a structural correlate of communication between the active site and the RNA‐sequestering thumb, we have solved the structure of a catalytically inactive point mutant of TruB in complex with a substrate RNA, and compared it to the previously determined structure of an active TruB bound to a reaction product. Superposition of the two structures shows that they are extremely similar, except in the active site and, intriguingly, in the relative position of the thumb. Because the two structures were solved using isomorphous crystals, and because the thumb is very well ordered in both structures, the displacement of the thumb we observe likely reflects preferential propagation of active site perturbations to this RNA‐binding domain. One of the interactions between the active site and the thumb involves an active site residue whose hydrogen‐bonding status changes during the reaction. This may allow the peripheral RNA‐binding domain to monitor progress of the pseudouridylation reaction.
Host use strategies of individual female brown‐headed cowbirdsMolothrus aterin a diverse avian community
Authors: Strausberger Bill M. , Ashley Mary V.
Published: June 2005

Although it is well established that brown‐headed cowbirdsMolothrus aterare host generalists, the parasitism strategies of individual females are not well documented. Here we use microsatellite genotyping to characterize host use by individual female cowbirds. Of 205 offspring sampled at a site in northeastern Illinois during one breeding season, we identified or inferred 33 mothers of 141 offspring, with up to 13 (mean 4.72) offspring assigned to individual females. Most (83%) females were host generalists and parasitized up to five host species, indicating that community‐wide patterns of parasitism do not result from different individuals specializing on different host species. However, some females (17%) parasitized a single species, suggesting that alternative host‐use strategies may exist within a single population. For host generalist females, individuals often parasitized host species that differed in body mass, nest‐site placement, and quality, indicating that female cowbirds exhibit extremely flexible host ranges. However, female cowbirds consistently discriminated among potential hosts, for example, by completely avoiding some common, but unsuitable species.
Perceived risk of ectoparasitism reduces primary reproductive investment in tree swallowsTachycineta bicolor
Authors: O'Brien Erin L. , Dawson Russell D.
Published: June 2005

Many birds have been shown to reduce their reproductive investment in response to infestation of nest sites by ectoparasites. Nest‐dwelling parasite populations increase throughout the breeding season, and can reduce the condition and future survival of both breeding adults and their offspring. Thus, avian hosts should be capable of assessing early cues that predict future ectoparasitism risk, and should be able to facultatively adjust their primary reproductive investment in response to anticipated future costs of parasites. We tested this hypothesis in the tree swallowTachycineta bicolor, a cavity nesting passerine, by presenting a visual cue of avian fleas on the outer surface of nest boxes. This treatment manipulated perceived ectoparasitism risk without exposing birds to parasites, thereby allowing us to examine facultative responses in the absence of early physiological effects of parasites on female reproductive investment. During one of the study years, birds preferentially occupied control boxes, however, across both years, birds nesting in treatment boxes produced significantly smaller clutches, resulting in smaller broods at hatching, relative to those in control boxes. This difference in clutch size could not be explained by differences in phenotypic quality of breeding birds, indicating that for cavity nesting birds such as tree swallows, the perception of future ectoparasitism risk may be sufficient to induce a facultative reduction in reproductive investment early in the breeding season, before nest‐dwelling parasite populations have grown very large.
Treatment outcomes for adolescent ectodermal dysplasia patients treated with dental implants
Authors: SWEENEY I. P. , FERGUSON J. W. , HEGGIE A. A. , LUCAS J. O.
Published: June 2005

To evaluate dental implant survival in patients with ectodermal dysplasia (ED). To assess patterns of hypodontia in this patient group.

Methods.  A retrospective analysis of the use of dental implants in ED patients treated at the Royal Children's Hospital, Melbourne.

Results.  Sixty‐one implants were placed into 14 patients (nine male and five female). The mean age of patients receiving maxillary implants was 18 years 6 months (range 17 years 9 months−20 years 0 months) and mandibular implants was 17 years 5 months (range 12 years 2 months−21 years 11 months). The mean follow‐up period was 3 years 4 months (range 1 year 18 months−5 years 1 month). Forty‐three implants were placed in the anterior mandible, three in the posterior mandible and the remaining 15 in the anterior maxilla.

 Of the 61 implants placed, 54 [88·5%] successfully integrated and were able to be restored. Three of the 15 implants placed into the anterior maxilla [20%] failed, while four of the 46 in the anterior mandible failed [8·7%]. Five of the 14 patients [35·7%] had at least one implant fail prior to abutment connection.

 At the 12‐month review appointments, 41 of the integrated 54 implants [76%] were reviewed and classed as successful, giving an overall success at follow up of 67·2%. Thirteen implants [21·3%] were unable to be reviewed owing to geographical reasons.

 Teeth most likely to be present in the maxilla were the central incisors [71%], first molars [54%] and canines [43%], whereas in the mandible they were the canines [53%] and the first premolars and first molars [40%].

Conclusions.  Dental implants can be placed, restored and loaded in ED patients. Maxillary teeth most likely to be present are the central incisors, canines and first molars, whereas in the mandible the canines, first premolars and molars are most likely to be present. Prior to cessation of growth, implant placement in the symphyseal region of the anterior mandible may be performed with caution. Despite the limited numbers and with due consideration to jaw development, the results support the continual use of endosseous dental implants in this group of patients for optimal clinical outcomes.
Restoration of severely decayed primary incisors using indirect composite resin restoration technique
Authors: MOTISUKI C. , SANTOS‐PINTO L. , GIRO E. M. A.
Published: June 2005

Caries of primary incisors is a common problem in paediatric dentistry in some countries. The restoration of primary incisors which have been severely damaged by early childhood caries or trauma is also a difficult challenge for clinicians. This case report describes an indirect technique for the restoration of primary anterior teeth using composite resin reinforced with a fibreglass post. Over a one‐year period, the crowns have demonstrated good retention and aesthetic results. The restorations were provided in two short chair‐side sections, with satisfactory patient cooperation.
Pain: a review of three commonly used pain rating scales
Authors: Williamson Amelia , Hoggart Barbara
Published: June 2005

Aims and objectives.  This review aims to explore the research available relating to three commonly used pain rating scales, the Visual Analogue Scale, the Verbal Rating Scale and the Numerical Rating Scale. The review provides information needed to understand the main properties of the scales.

Background.  Data generated from pain‐rating scales can be easily misunderstood. This review can help clinicians to understand the main features of these tools and thus use them effectively.

Method.  A MedLine review via PubMed was carried out with no restriction of age of papers retrieved. Papers were examined for methodological soundness before being included. The search terms initially included pain rating scales, pain measurement, Visual Analogue Scale, VAS, Verbal Rating Scale, VRS, Numerical/numeric Rating Scale, NRS. The reference lists of retrieved articles were used to generate more papers and search terms. Only English Language papers were examined.

Conclusions.  All three pain‐rating scales are valid, reliable and appropriate for use in clinical practice, although the Visual Analogue Scale has more practical difficulties than the Verbal Rating Scale or the Numerical Rating Scale. For general purposes the Numerical Rating Scale has good sensitivity and generates data that can be statistically analysed for audit purposes. Patients who seek a sensitive pain‐rating scale would probably choose this one. For simplicity patients prefer the Verbal Rating Scale, but it lacks sensitivity and the data it produces can be misunderstood.

Relevance to clinical practice.  In order to use pain‐rating scales well clinicians need to appreciate the potential for error within the tools, and the potential they have to provide the required information. Interpretation of the data from a pain‐rating scale is not as straightforward as it might first appear.
Risk management of extravasation of cytostatic drugs at the Adult Chemotherapy Outpatient Clinic of a university hospital
Authors: Adami Nilce Piva , De Gutiérrez Maria Gaby Rivero , Da Fonseca Selma Montosa , De Almeida Elizabeth Pinto Magalhães
Published: June 2005

Aims and objectives.  To verify the incidence of extravasation of cytostatic drugs in patients treated on an outpatient basis at a university hospital in the city of São Paulo, Brazil, during the period from 1998 to 2002, and to assess the quality of care provided by the nursing team using a protocol adopted for the treatment of this adverse event as a parameter.

Background.  The movement for quality in healthcare services has been a recent event in Brazil, mainly as the result of the Brazilian Program of Hospital Accreditation instituted in 1998. Considering the emphasis on risk management, it is important to mention the monitoring of the occurrence of extravasations of cytostatic drugs in order to improve the quality of nursing care provided to cancer patients.

Design and methods.  An evaluative study with a descriptive, prospective and longitudinal design was conducted, based on the documentary analysis of the notification of 216 extravasations of vesicant and irritant drugs that occurred between 1998 and 2002 and the corresponding prescriptions of cold or hot compresses.

Results.  The mean incidence of extravasations ranged from 0·2 to 1·4% over the five years of the study. Incorrect prescription of the type of compress was observed for three patients. Undesired effects were ulcers caused by the extravasation of vinblastine and dacarbazine in two cases.

Conclusions.  The low incidence of both extravasation and tissue damage demonstrates the adequate quality of nursing care provided to cancer patients at the outpatient clinic studied. However, the identification of the lack of 12 records of thermal treatment and of three erroneous prescriptions requires the implementation of educational measures to prevent these types of incident.

Relevance to clinical practice.  The relevance of this study to clinical practice is to increase the awareness and involvement of the nursing team in the maintenance of a continuous surveillance system of the process and results of chemotherapy administration in order to increase the quality of care and the safety of the patient.
Obesity: translation and testing of a survey instrument for use in Taiwan
Authors: Hsieh Pei‐Lin , Cholowski Krystyna , FitzGerald Mary
Published: June 2005

Aim and objectives.  The purpose of this paper is to describe a cross‐cultural translation and validation methodology recommended by Vallerand. The translation technique has seven steps and ensures the instrument provides data that are valid and reliable.

Background.  Translation of data collection instruments is a challenge increasingly being faced by overseas students studying in the West as they choose to research contextual issues of relevance to their home culture.

Methods.  Six of Vallerand's seven steps are used and modified as the methodical translation of a survey from English to Mandarin.

Results.  The results revealed there was no significant difference between the original English questionnaire and Mandarin questionnaire. The validation study indicated good internal consistency. The construct validity of the Mandarin version was determined except one item which failed the test. The validation demonstrates only minor effects of language translation.

Conclusion.  The Mandarin version thus is a valid tool for investigating from the perspective of school nurses, their role and potential contribution to health promotion in relation to the prevention of obesity among school children in Taiwan.

Relevance to clinical practice.  The results of the study will enable school nurses and their managers to reflect critically on their contribution to the prevention of obesity among Taiwanese school children. The translation technique has enabled the researcher to minimize errors that may have occurred in translation. It adds to the quality of the instrument and offers opportunities in the future to undertake cross‐cultural comparison in an issue of great concern globally.
Lucidity in a woman with severe dementia related to conversation. A case study
Authors: Normann Hans Ketil , Henriksen Nils , Norberg Astrid , Asplund Kenneth
Published: June 2005

Aims and objectives.  The aim of this study was to explore the presence of lucidity in a woman with severe dementia during conversations and whether it occurred when conversational partners or the woman with severe dementia initiated the conversation topics about the present, past or future time and whether she was presented with support or demands during the conversation.

Background.  Communication problems as well as episodes of lucidity in people with dementia are reported in the literature.

Design.  A researcher held 20 hours of conversation with a woman with severe dementia. A daughter participated for about three and a half hours. The conversation was tape‐recorded and transcribed verbatim.

Methods.  The text was divided into units of analysis. Each unit of analysis was then assessed separately and discussed among the authors. Chi‐square tests and logistic regression analysis were performed. An ethics committee approved the study.

Results.  The woman as initiator of the conversation topic and support to the women during conversation from the conversation partner were found to be the most significant factors explaining lucidity, while conversation about the present or past time showed no connection with lucidity. Very few topics (n = 7) concerned future time and they were not used in the statistical analysis. The researcher initiated 41%, the woman 43% and the daughter 16% of the topics. Support was registered in 49%, demands in 15% and both support and demands in 16% of the units of analysis. There were 58% topics about present and 40% about the past time.

Conclusions.  The presented study is a case study and the results cannot be generalized. For the woman with severe dementia, lucidity was promoted by the conversational parties carefully focusing on conversation topics initiated by the woman while supporting her during conversation.

Relevance to clinical practice.  To share the same perception of reality, focusing on the topics initiated by the patient with severe dementia and a supporting attitude to what the patient tells, will hopefully give more episodes of lucidity in the patient. This approach in caring for patients with severe dementia might give more meaning and well‐being to the conversational partners in daily care.
The nature of nursing care and rehabilitation of female stroke survivors: the perspective of hospital nurses
Authors: Kvigne Kari , Kirkevold Marit , Gjengedal Eva
Published: June 2005

Aims and objectives.  The aim of this study was to explore the nature of nursing care and rehabilitation of female stroke survivors, as described by hospital nurses. The objectives were to uncover how the nurses perceived the care of female stroke survivors and to explore whether, and in what way, the nurses paid attention to the fact that the patients were women.

Background.  Nursing care is an important aspect of the rehabilitation of stroke survivors. Little attention has been paid to gender differences in the health care system in general and in the nursing profession in particular, although it is reasonable to think that gender issues may have important implications in the rehabilitation process following a stroke.

Design.  Design was phenomenological with feminist perspective.

Methods.  The nurses were interviewed in‐depth. In the data analysing process we were inspired by Giorgi's phenomenological method.

Results.  The nurses were focusing primarily on functional and practical aspects of the women's situation. They perceived the rehabilitation process predominately from a professional rather than the patient point of view, and from a non‐conscious and primarily gender‐neutral perspective.

Conclusions.  The results indicate that the nurses perceived nursing care primarily in terms of practical actions to promote the body's functional and practical abilities. Little attention was directed to the stroke survivors’ experiences of their life body, nor to the fact that the patients were women.

Relevance to clinical practice.  In order to promote care from the perspective of the female stroke survivors, we believe it is necessary to attend to the life experiences of the patient, which also mandates paying attention to how gender has an impact on their diseased bodies, every day life, values and preferences in the situation.
Nurse consultants: their characteristics and achievements
Authors: Woodward Valerie A , Webb Christine , Prowse Morag
Published: June 2005

Aim.  This paper reports one aspect of a larger study of nursing research strategies in one English region, focusing particularly on nurse consultants’ characteristics and achievements in the role.

Background.  Nurse consultant posts have only been established in the United Kingdom since 1999 and, although much comment has appeared in the professional literature, there is very little research‐based evidence of how the roles are developing. The role is intended to integrate four domains: expert practice; professional leadership and consultancy; education, training and development; and practice and service development.

Design.  A cross‐sectional design, using a convenience sample, was adopted.

Methods.  Ten nurse consultants working in a variety of settings and specialties participated in in‐depth, tape‐recorded interviews. The data were analysed using the Framework approach.

Results.  Four themes were identified from the data: characteristics of the postholder, role achievement, support systems and National Health Service influences. The first two themes are discussed in this paper and the data show that the nurse consultants varied in terms of their academic background and previous experience. Not all had the recommended minimum of Master's degree level preparation and some had limited research experience. These background characteristics seemed to influence the degree to which they were able to achieve the four domains of the role, with those with lower qualifications and from a mental health background appearing to struggle most.

Conclusions.  New appointments to these roles should only be made when candidates possess the recommended levels of educational preparation and professional experience of change management. It is also important that there is clarity about the scope of the role, which should not include management responsibilities. On‐going research is essential to evaluate how the roles develop for postholders, the extent to which they fulfil policymakers’ expectations and what difference they make to patient care from a patient perspective.

Relevance to clinical practice.  The findings show that holders of such posts need to have appropriate previous knowledge, skills and personal characteristics, as these seem to influence their ability to integrate the four domains of the role and thus achieve the requirements of the post.
The early development of self‐injurious behaviour: evaluating the role of social reinforcement
Authors: Oliver C. , Hall S. , Murphy G.
Published: June 2005

Background  The potential role of social reinforcement in the development of self‐injury has not yet been subjected to empirical analysis. In this 2‐year prospective study, the pattern of social interactions related to the early presentation of self‐injury were examined to identify a potential association with an increase in self‐injury.

Methods  The self‐injurious behaviour and social contact with adults of 16 children with intellectual disability (ID) with self‐injury of recent onset were observed at 3‐month intervals over 2 years.

Results  Increase in self‐injury over a 2‐year period was positively correlated with a distribution of social contact relative to episodes of self‐injury that is consistent with a mutual social reinforcement paradigm. When this paradigm was operative, self‐injury was evoked under stable antecedent conditions over time but tended to evoke increasing levels of social interaction.

Conclusions  These results support the hypothesis that increases in the frequency of early self‐injury in children with ID may be determined by social reinforcement with implications for early intervention and proactive identification of children at risk for increases in self‐injury.
Fair shares? Supporting families caring for adult persons with intellectual disabilities
Authors: McConkey R.
Published: June 2005

Background  Although the majority of adult persons with intellectual disabilities are cared for by their families, remarkably little is known of the characteristics of their carers, the support services they receive and their unmet needs. A particular concern is whether or not carers have equitable access to services.

Method  Information was gathered from service staff who knew best the person with the disability. A standard pro forma was used with a representative sample of over 1500 family carers in Northern Ireland (26% of the estimated population).

Results  Nearly half of the people were being cared for by both parents, but around one third lived with lone carers and 20% with another relative. These subgroups of carers varied significantly in their personal characteristics and in terms of the person for whom they cared. However, Regression Analyses identified that their relative's higher dependency in person care was the only common variable that was predictive of carers’ access to support services. A possible measure of unmet need for various support services was derived.

Conclusions  Services need to pay greater attention to the characteristics of family carers so as to overcome some of the present inequities in supports offered to them. Further areas for future research are identified.
An investigation of executive function abilities in adults with Prader–Willi syndrome
Authors: Walley R. M. , Donaldson M. D. C.
Published: June 2005

Background  Prader–Willi syndrome (PWS) is a genetic disorder caused by the absence of expression of maternally imprinted genes on the long arm of chromosome 15 (15q 11‐13). There are two main genetic sub‐types: (1) deletion, caused by the absence of paternally derived genetic material; and (2) uniparental disomy (UPD), where two copies of maternally derived chromosome 15 are present. In addition to generally mild/borderline intellectual disability (ID) and the almost universal feature of hyperphagia, PWS is associated with high rates of behaviour problems including temper tantrums, compulsive behaviour, perseverative speech, skin picking and rigid thinking. The present study seeks to explore whether these behaviours are associated with relative deficits in executive function (EF), which comprises the set of non‐automatic processes utilized by an individual when faced with a novel situation.

Methods  Eighteen adult participants with a clinical diagnosis of PWS (12 with deletion sub‐type, 6 with UPD) were recruited from a UK Health Service PWS clinic, and compared with 15 participants of similar age and verbal ability on a series of EF tasks and also Digit Span Forwards. An informant completed two ratings of behaviour, the Aberrant Behavior Checklist (ABC) and the Dysexecutive Questionnaire (DEX).

Results  The PWS group had significantly higher scores on the ABC but not on the DEX. There were no significant differences between the whole PWS group and the comparison group on any of the EF tasks. The deletion sub‐type group was significantly poorer at a non‐executive task, Digit Span Forwards. There was an unexpected trend for the deletion sub‐type group to show more efficient performance on a visuospatial planning task, the Tower of London (TOL), but this trend did not reach significance.

Conclusions  The lack of relative deficits in EF task performance does not support the hypothesis that EF differences could account for the high levels of behaviour problems found in PWS. Applying the Baddeley and Hitch model of working memory it is suggested that the PWS group have a relatively intact central executive and visuospatial sketchpad but a relative impairment in the phonological loop, perhaps relating to the capacity of the phonological store. This latter finding seems to be particularly salient for those with a deletion. As differences in EF ability were not found, it is suggested that a region of the brain involved in the modulation of emotion but not particularly with EF, the orbitofrontal cortex (OFC), may be implicated in the behaviour problems reported in PWS.
Treatment of chronic hepatitis B
Authors: Marcellin P. , Asselah T. , Boyer N.
Published: June 2005

Summary.  In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available, is limited by the high incidence of resistance. Adefovir, which was recently approved has a comparable efficacy with a very low frequency of resistance. However, adefovir needs to be indefinitely administered as withdrawal of therapy is generally associated with reactivation and sustained response is uncommon.

Recent large randomized controlled trials showed that PEG IFNs induce relatively high sustained response rates both in HBeAg positive and HBeAg negative chronic hepatitis B. So far, the combination of PEG IFN with lamivudine, used simultaneously, is disappointing in terms of short‐term efficacy. However, long‐term efficacy needs to be assessed and different schedules of combination (for example sequential) need to be evaluated.

A number of nucleoside analogues, with favourable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir and emtricitabine confirmed their efficacy. However, while entecavir is associated with a low incidences of resistance, emtricitabine is associated with a relatively high incidence of resistance which limits its use as a monotherapy. The efficacy and safety of new and more potent drugs like telbivudine and clevudine need to be confirmed.

The future of chronic hepatitis B therapy seems to be in the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should have different sites of action on HBV DNA replication, a potent antiviral effect, an excellent safety profile and they should induce a sustained response with a limited duration of therapy. Indeed, the concept of combination therapy has been recently developed in order to increase efficacy and to decrease the occurrence of viral resistance. However, so far few combinations have been evaluated. No combination therapy demonstrated a benefit as compared with monotherapy. More potent drugs and new combinations together with the understanding of the mechanisms of resistance to therapy are important challenges to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.
The relationship between HBV‐DNA levels and cirrhosis‐related complications in Chinese with chronic hepatitis B
Authors: Yuan H.‐J. , Yuen M.‐F. , Ka‐Ho Wong D. , Sablon E. , Lai C.‐L.
Published: June 2005

Summary.  We studied the hepatitis B virus (HBV)‐DNA levels below which the development of cirrhosis‐related complications became unlikely in chronic hepatitis B (CHB). Seventy‐nine Chinese CHB patients with cirrhosis‐related complications and 158 age‐, sex‐ and HBeAg status‐matched patients without complications were enrolled. The precore and core promoter mutations were detected by the Line Probe assay (LiPA). HBVDNA levels were determined by Digene assay and Cobas Amplicor Monitor test. Patients with complications had higher HBVDNA levels than those without complications (P = 0.02). HBeAg‐positive patients with complications had similar alanine transferase (ALT) and HBVDNA levels and frequency of precore mutations, but higher frequency of core promoter mutations (P = 0.003), compared with those without complications. Anti‐HBe‐positive patients with complications had higher ALT and HBVDNA levels (P < 0.01) but similar frequency of precore and core promoter mutations, compared with those without complications. Anti‐HBe patients (24.5%) with complications had HBVDNA levels <104 copies/mL. The major factor for the development of cirrhotic complications was viral loads but cirrhotic complications continued to develop in patients with HBVDNA levels below 104 copies/mL.
Safety and efficacy of peginterferon plus ribavirin in patients with chronic hepatitis C and bridging fibrosis or cirrhosis
Authors: Marrache F. , Consigny Y. , Ripault M. P. , Cazals‐Hatem D. , Martinot M. , Boyer N. , Degott C. , Valla D. , Marcellin P.
Published: June 2005

Summary.  The combination of pegylated interferon and ribavirin is the most effective therapy in patients with chronic hepatitis C. We evaluated this combination in unselected patients with bridging fibrosis or cirrhosis. Eighty patients were treated with peginterferon alpha‐2b plus ribavirin. Hepatitis C virus serum RNA was monitored. Tolerance and safety were evaluated by the rate of treatment's discontinuation for any reason, and occurrence of serious clinical adverse events, respectively. Sustained virologic response (SVR) rate was 36.3% overall, and was observed in every group of patients except those who had previously failed to respond to the combination of interferon and ribavirin. No serious clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients. Variables associated with discontinuation of treatment were low prothrombin index [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial blood count abnormalities were not associated with cessation of treatment. Furthermore, early virologic response at week 8 and week 12 of treatment had similar predictive value for SVR. Combination therapy with peginterferon plus ribavirin seems effective in this group of patients, except in those who had previously failed to respond to the combination of interferon and ribavirin. This therapy is safe with appropriate monitoring, but tolerance seems worse in patients with the most advanced liver disease.
Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and hammerhead ribozymes
Authors: Nash K. L. , Alexander G. J. M. , Lever A. M. L.
Published: June 2005

Summary.  Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. Current treatments are limited and may be ineffective. Nucleic acid‐mediated targeting of viral mRNA is an attractive and specific approach for viral infection and lentiviral vectors provide a means to express antisense sequences or ribozymes stably in target cells permitting continuous production within that cell and its progeny. To demonstrate long‐term gene expression by lentiviral vectors in hepatocytes and to introduce lentiviral vectors expressing anti‐HBV genes to assess their effect against HBV, lentiviral vectors expressing a reporter gene were assessed for longevity of gene expression in hepatocytes in vitro. Hammerhead ribozymes and antisense sequences targeting the HBV encapsidation signal (ε), X or surface antigen on mRNAs were cloned into lentiviral vectors and used to transduce HBV expressing hepatocytes where the effect on HBV mRNA level was assessed using ribonuclease protection. Gene expression in hepatocytes from integrated vectors continued for over 4 months without selection. Antisense RNA targeting HBs mRNA reduced this transcript, whilst antisense RNA to HBX mRNA was ineffective. Sense RNAs corresponding to ɛ and HBX mRNA also reduced HBV mRNA levels. Ribozymes targeting HBs and HBX mRNA effectively reduced HBV mRNA levels compared with inactive constructs indicating their effect to be enzymatic rather than antisense. Lentiviral vectors can produce long‐term gene expression in hepatocytes and thus permit prolonged expression of antiviral genes targeting the HBV encapsidation signal, surface and X mRNAs as treatments for chronic HBV infection.
Age‐specific antibody to hepatitis E virus has remained constant during the past 20 years in Japan
Authors: Tanaka E. , Matsumoto A. , Takeda N. , Li T.‐C. , Umemura T. , Yoshizawa K. , Miyakawa Y. , Miyamura T. , Kiyosawa K.
Published: June 2005

Summary.  We investigated the presence of antibodies to hepatitis E virus (anti‐HEV) and hepatitis A virus (anti‐HAV) by enzyme immunoassays in sera from 1015 individuals collected in 1974, 1984 and 1994. Age‐specific profiles of anti‐HEV remained unchanged with a peak at 40–49 years, while those of anti‐HAV started to increase in individuals aged 20–29 years in 1974, 30–39 years in 1984 and 40–49 years in 1994. These results suggest that a silent HEV infection has been taking place in the last 20 years or so in Japan, while HAV infection has been terminated at least since 1974.
Effects of branched β‐carbon dehydro‐residues on peptide conformations: syntheses, crystal structures and molecular conformations of two tetrapeptides: (a) N‐(benzyloxycarbonyl)‐ΔVal‐Leu‐ΔPhe‐Leu‐OCH3 and (b) N‐(benzyloxycarbonyl)‐ΔIle‐Ala‐ΔPhe‐Ala‐OCH3
Authors: Goel V.K. , Somvanshi R.K. , Dey S. , Singh T.P.
Published: June 2005

Abstract:  The roles of branched β‐carbon dehydro‐residues in the design of peptide conformations have not been systematically explored so far. In order to determine the effects of branched β‐carbon dehydro‐residues on the peptide conformations, two N‐protected tetrapeptides containing new combinations of ΔVal and ΔPhe in (a) N‐(benzyloxycarbonyl)‐ΔVal‐Leu‐ΔPhe‐Leu‐OCH3 and ΔIle and ΔPhe in (b) N‐(benzyloxycarbonyl)‐ΔIle‐Ala‐ΔPhe‐Ala‐OCH3 were synthesized by solution procedure. The crystal structures of these peptides were determined by X‐ray diffraction methods. Single crystals of both peptides were grown by slow evaporation method from their solutions in acetone–water mixtures (80 : 20) at 25 °C. The crystals of these peptides belong to the orthorhombic space group P212121 with cell dimensions of a = 12.342(1) Å, b = 15.659(1) Å, c = 18.970(1) Å for peptide (a) and a = 8.093(1) Å, b = 15.791(1) Å, c = 23.816(1) Å for peptide (b) having Z = 4 in the unit cells of both peptides. The structures were refined by full‐matrix least‐squares procedure to R‐factors of 0.076 and 0.052 respectively. Both peptides adopt the right‐handed 310‐helical conformations stabilized by two intramolecular (i + 3→i) hydrogen bonds between the CO of N‐terminal benzyloxycarbonyl (Cbz) group and the NH of residue at position 3, and between the CO of residue at position 1 and NH of the residue at position 4. The two consecutive 10‐membered rings formed by the hydrogen bonds have dihedral angles corresponding to the standard values for type III β‐turns. ΔVal and ΔIle in peptides (a) and (b) respectively are located at the (i + 1) position of the first β‐turn while ΔPhe is located at the (i + 2) position of the second β‐turn. In the crystals, the molecules are linked head to tail by intermolecular hydrogen bonds to form long helical chains. The axes of helices are parallel to the b‐axes while the neighbouring helices run in the opposite directions. The crystal packings are further stabilized by van der Waals forces between the columns of molecular packings.