bluuebunny/crossref_metadata_2025 huggingface dataset:
A stage‐structured model to predict the effect of temperature and salinity on glass eel Anguilla anguilla pigmentation development
Authors: Briand C. , Fatin D. , Ciccotti E. , Lambert P.
Published: October 2005

The pigmentation development process of glass eels Anguilla anguilla from stage VB to VIA3 was modelled by gamma cumulative functions. These functions varied with respect to the factors temperature and salinity whose effects were adjusted by beta functions. Temperature was shown to accelerate pigmentation, while salinity acted as a secondary factor slowing down the pigmentation. The model fits the development of 15 samples kept at various temperatures and salinities in the Vilaine River, as well as samples monitored at other dates and places in Europe. It allows the prediction of the duration of estuarine residency for glass eels, in winter and spring, in the Atlantic estuaries.
Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies
Authors: Wouters Karlijn A. , Kremer Leontien C. M. , Miller Tracie L. , Herman Eugene H. , Lipshultz Steven E.
Published: September 2005

Over the last 40 years, great progress has been made in treating childhood and adult cancers. However, this progress has come at an unforeseen cost, in the form of emerging long‐term effects of anthracycline treatment. A major complication of anthracycline therapy is its adverse cardiovascular effects. If these cardiac complications could be reduced or prevented, higher doses of anthracyclines could potentially be used, thereby further increasing cancer cure rates. Moreover, as the incidence of cardiac toxicity resulting in congestive heart failure or even heart transplantation dropped, the quality and extent of life for cancer survivors would improve. We review the proposed mechanisms of action of anthracyclines and the consequences associated with anthracycline treatment in children and adults. We summarise the most promising current strategies to limit or prevent anthracycline‐induced cardiotoxicity, as well as possible strategies to prevent existing cardiomyopathy from worsening.
Immunological control of methicillin-resistantStaphylococcus aureus(MRSA) infection in an immunodeficient murine model of thermal injuries
Authors: Katakura T , Yoshida T , Kobayashi M , Herndon D N , Suzuki F
Published: September 2005

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns. In this study, an immunological regulation of MRSA infection was attempted in a mouse model of thermal injury. SCIDbg mice were resistant to MRSA infection, while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mφ)) were susceptible to the same infection. Also, thermally injured SCIDbg mice were shown to be susceptible to MRSA infection. On the other hand, the resistance of SCIDbgMN mice to the infection was completely recovered after an inoculation with Mφ from normal mice. However, anti-MRSA resistance was not shown in SCIDbgMN mice inoculated with Mφ from thermally injured mice. Mφ from MRSA-infected thermally injured mice were identified as alternatively activated Mφ, and Mφ from MRSA-infected unburned mice were characterized as classically activated Mφ. Mφ from thermally injured SCIDbg mice previously treated with 2-carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA infection. Ge-132 has been described as an inhibitor of alternatively activated Mφ generation. These results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti-MRSA effector cells and elimination of burn-associated alternatively activated Mφ, which are cells that inhibit the generation of classically activated Mφ.
Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism
Authors: Moosgaard B. , Vestergaard P. , Heickendorff L. , Melsen F. , Christiansen P. , Mosekilde L.
Published: September 2005

Background  Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that can occur in combination. However, low plasma 25‐hydroxyvitamin D (25OHD) may also enhance the risk of PHPT or modify disease severity.

Aim  To compare the risk of vitamin D insufficiency and deficiency stratified by age, sex and season between PHPT patients and controls and to assess associations between plasma 25OHD and adenoma weight, biochemical variables, bone mineral density (BMD) and clinical complications.

Design  Cross‐sectional study.

Material  A total of 289 consecutive Caucasian patients with PHPT aged 65·9 (24–92) years, 289 sex‐, age‐ and season‐matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration.

Results  Vitamin D insufficiency (plasma 25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex‐ and age‐matched controls (P < 0·001) and 35% of blood donors (P < 0·001). During summer, 77%vs. 53% (P < 0·001) and 4% (P < 0·001), respectively, had vitamin D insufficiency. Average plasma 25OHD was 41 (range 9–87) nmol/l among 27 PHPT patients compared with 87 (21–173) nmol/l (P < 0·001) among aged‐matched blood donors. During winter, 86%vs. 66% (P < 0·001) and 71% (P < 0·05), respectively, had vitamin D insufficiency. Vitamin D deficiency (plasma 25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age‐ and sex‐matched controls (P < 0·001) and 13% of blood donors (P < 0·001). Both PHPT patients and controls showed seasonal variations in 25OHD related to the average number of sun hours, but values were lower in PHPT patients at all calendar months. In PHPT patients low plasma 25OHD was associated with higher plasma levels of calcium, PTH and alkaline phosphatase and with lower renal calcium excretion, femoral neck and forearm BMD. No association was found between plasma 25OHD and adenoma weight (total or divided into tertiles). There was a trend towards increased risk of osteoporotic fractures (P < 0·08) with low plasma 25OHD.

Conclusion  Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex‐ and age‐matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.
Adaptation of the hypothalamic‐pituitary hormones during intensive endurance training
Authors: Bobbert T. , Brechtel L. , Mai K. , Otto B. , Maser‐Gluth C. , Pfeiffer A. F. H. , Spranger J. , Diederich S.
Published: September 2005

Objective  Physical activity leads to changes in the hypothalamic‐pituitary hormonal system. However, acute and long‐term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic‐pituitary‐adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11β‐hydroxysteroid‐dehydrogenase system (11β‐HSD).

Design  Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24‐h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon.

Results  Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11β‐HSD‐1 was up‐regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic‐pituitary‐hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training.

Conclusions  The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11β‐HSD system. Changes in the other hypothalamic‐pituitary hormonal axes were the result of long‐term differences in training levels and were not altered by the marathon.
Contributions of incorporated residue and living roots to aggregate‐associated and microbial carbon in two soils with different clay mineralogy
Authors: Denef K. , Six J.
Published: October 2005

We conducted a study to investigate the role of aggregates in the stabilization of residue‐ and root‐derived C in an illitic Mollisol and a kaolinitic Oxisol under the following treatments: (i) incorporated residue, (ii) growing plants, and (iii) both incorporated residue and growing plants. Residue‐C dynamics were followed in soils incubated with 13C‐labelled wheat residue with and without unlabelled growing wheat plants. Root‐C was traced by growing wheat plants with and without unlabelled wheat residue in a 13CO2‐labelling chamber. After 46 and 76 incubation days, residue‐ and root‐C were measured in four aggregate size classes and in microbial‐C. Both soils had greater residue‐derived than root‐derived total aggregate‐associated C at day 76, which we attributed to the larger residue‐C than root‐C inputs at the start of the experiment. On an aggregate basis, the ratio of residue‐derived over root‐derived C decreased in most size fractions over time, indicating a greater potential for longer‐term root‐C than residue‐C stabilization by aggregates in both soils. At both sampling days, all aggregates > 53 µm had greater residue‐C concentrations in the illitic soil than in the kaolinitic soil and this difference increased with increasing aggregate size. This suggested a greater affinity of illite clay than kaolinite clay to bind with fresh residue‐derived compounds into larger aggregates and hence a greater importance of aggregates in stabilizing residue‐C in illitic compared with kaolinitic soils. The stabilization of root‐C by aggregates was less affected by clay mineralogy and thus less dependent on the affinity of clay minerals to bind with root‐derived compounds.
Defoliation‐induced changes in carbon allocation and root soluble carbon concentration in field‐grown Lolium perenne plants: do they affect carbon availability, microbes and animal trophic groups in soil?
Authors: BAZOT S. , MIKOLA J. , NGUYEN C. , ROBIN C.
Published: September 2005

It is hypothesized that defoliation‐induced changes in plant carbon allocation and root soluble C concentration modify rhizosphere C availability and, further, the abundance and activity of soil microbes and their grazers. To test this hypothesis, field‐grown Lolium perenne swards were defoliated twice during their second growing season at two nitrogen availabilities (added N or no added N). Plant, soil and microbial attributes were measured 2 and 4 days after the last defoliation, and nematode abundance was measured 6 days after the last defoliation.

Defoliation decreased shoot production in plots where N was added, but had no significant effect in plots where N was not added. Root biomass and the ratio of root mass to shoot production were not affected.

Defoliation increased root soluble C concentration by 26% at the first harvest (2 days after defoliation) and by 18% at the second harvest (4 days after defoliation). Leaf N concentration was 27% lower in defoliated than in non‐defoliated swards at the first harvest, while that of stems was 14% higher in defoliated swards at both harvests, and that of roots was not affected. Defoliation increased root C : N ratio, decreased stem C : N ratio, and did not have a statistically significant effect on leaf C : N ratio.

Soil attributes (soil soluble C concentration and soil C and N concentrations) were not affected by defoliation. Similarly, microbial attributes such as microbial C and N content, bacterial abundance in rhizosphere soil, and diversity of C sources utilized by the rhizosphere microbial community, did not differ between defoliated and non‐defoliated swards.

Among nematode trophic groups, defoliation reduced the abundance of fungivorous and herbivorous nematodes by 70 and 47%, respectively, but did not affect the abundance of bacterivorous, omnivorous and predatory nematodes.

Although defoliation altered plant C allocation and root soluble C concentration, these changes did not influence C availability, soil microbial growth or the abundance of bacteria‐feeding nematodes in the plant rhizosphere. Instead, the effects on root‐ and fungus‐feeding nematodes suggest that the effects of defoliation on soil communities were propagated not through the effects of root‐released C on bacteria and bacterial grazers, but through effects of root quality on root‐feeders and possibly through effects of mycorrhizal fungi on fungus‐feeders.
SHORT NOTE: AnoBase: a genetic and biological database of anophelines
Authors: Topalis P. , Koutsos A. , Dialynas E. , Kiamos C. , Hope L. K. , Strode C. , Hemingway J. , Louis C.
Published: September 2005

AnoBase (http://www.anobase.org) is an integrated, relational database of basic biological and genetic data on anopheline species, with a particular emphasis on Anopheles gambiae. It has been designed as an information source and research support tool for the broad vector biology community. Although AnoBase is not a primary genomic database that develops and provides tools to access the genome of the malaria mosquito, it nevertheless contains several sections that offer data of genomic interest such as in situ hybridization images, an integrated gene tool and direct online access to AnoXcel, the proteomic database of An. gambiae. Moreover, AnoBase also contains information on non‐gambiae mosquito species and a novel section on studies related to insecticide resistance.
Role of dopachrome conversion enzyme in the melanization of filarial worms in mosquitoes
Authors: Huang C.‐Y. , Christensen B. M. , Chen C.‐C.
Published: September 2005

Melanization is an effective defence reaction of mosquito hosts against invading parasites. In mosquitoes, the biosynthesis of melanin is initiated by the hydroxylation of tyrosine to DOPA by phenoloxidase (PO). DOPA is a branch point of the melanization reaction; it may be oxidized to dopaquinone by PO or be decarboxylated to dopamine by dopa decarboxylase. Further oxidation of dopaquinone by PO produces dopachrome. Dopachrome is then converted to 5, 6‐dihydroxyindole by dopachrome conversion enzyme (DCE) to produce melanin. The conversion of dopachrome is a rate‐limiting step of the melanization reaction, and the presence of PO and DCE significantly accelerates melanization reactions. In this study, a cDNA encoding DCE was cloned from the mosquito Armigeres subalbatus. Real‐time PCR analysis revealed increased transcripts from haemocytes in microfilariae (mf)‐inoculated mosquitoes. Gene silencing using double‐stranded RNA was used to elucidate the role of DCE in the melanization reaction of parasites in Ar. subalbatus. The levels of both DCE transcripts and protein in gene knockdown mosquitoes were dramatically reduced. Compared with controls, the degree of melanization of mf in DCE‐knockdown mosquitoes was significantly decreased. These results suggest that DCE is a critical enzyme that is required for effective melanization immune responses.
Swedish women's satisfaction with medical and emotional aspects of antenatal care
Authors: Hildingsson Ingegerd , Rådestad Ingela
Published: September 2005

Aim.  This paper reports a study to investigate how satisfied Swedish women are with their antenatal care.

Background.  Medical care is of high priority, but other aspects, such as psychosocial support are also important for women during pregnancy. Identifying women who are dissatisfied with their antenatal care could help us to improve this.

Methods.  A national cohort of 2746 Swedish‐speaking women completed a questionnaire in early pregnancy and at 2 months postpartum. The data were collected in 1999–2000.

Results.  The majority of participants were satisfied with their antenatal care, but 23% were dissatisfied with the emotional aspects and 18% with the medical aspects. The strongest predictors of dissatisfaction were women's opinions that midwives had not been supportive and had not paid attention to their partners’ needs. If the women believed that there were not enough antenatal visits or had met three or more midwives during their antenatal visits, they were more likely to be dissatisfied with the care received. Those with low levels of education were more likely to be dissatisfied with both medical and emotional aspects of antenatal care.

Conclusions.  Midwives working in antenatal care should support pregnant women and their partners in a professional and friendly way in order to increase satisfaction with care. Organizing teamwork with no more than two midwives taking care of a woman during a normal pregnancy could make women feel more supported by their midwives.
Nursing intervention after carotid endarterectomy: a randomized trial of Co‐ordinated Care Post‐Discharge (CCPD)
Authors: Middleton Sandy , Donnelly Neil , Harris John , Ward Jeanette
Published: September 2005

Aim.  This paper reports a study evaluating the short‐term impact of nursing‐led, co‐ordinated care after discharge following carotid endarterectomy.

Background.  Patient education about stroke risk factors, combined systematically with carotid endarterectomy, holds unrealized potential to improve patient outcomes. Nurses are well‐placed in the healthcare system to co‐ordinate this type of education.

Methods.  A randomized controlled trial was conducted between October 2001 and October 2002. Patients having carotid endarterectomy (n = 133) were randomized to either the intervention (n = 66) or control group (n = 67). The intervention consisted of telephone liaison with the patient by a Registered Nurse at 2, 6 and 12 weeks following carotid endarterectomy, combined with education about stroke risk factor management and structured liaison with the patient's surgeon and referring general practitioner. While patients allocated to the control group did not receive any postoperative telephone contact directly from the Registered Nurse during the study, their general practitioners received structured postoperative liaison.

Results.  The co‐ordinated care postdischarge intervention had a statistically significant positive effect on patient knowledge of stroke warning signs (P = 0·002), patient self‐reported changes to improve lifestyle (P = 0·006) and diet modification (P < 0·001). Statistically significant improvements from baseline to follow‐up were detected in both groups for other outcomes.

Conclusions.  While nursing‐led, co‐ordinated care after discharge achieves important improvements for short‐term outcomes, carotid endarterectomy itself may have been a catalyst for improved patient outcomes. Further research of nursing‐led co‐ordinated care initiatives for vascular surgery patients is needed.
Client–caregiver–nurse coalition formation in decision‐making situations during home visits
Authors: Dalton Joanne
Published: September 2005

Aims.  The purpose of this paper is to report the findings of an exploratory study designed to test a portion of the Theory of Collaborative Decision‐Making in Nursing Practice for Triads by examining the relation between types of decisions and formation of coalitions during triadic interactions among older home healthcare clients, their caregivers and home healthcare nurses during seven admission visits for home health care.

Background.  Although home healthcare nurses include clients and family members in decision‐making about care, few publications address the nature of interactions among triads of clients, caregivers and nurses in home health care and the association between decision‐making and those interactions.

Method.  The data presented in this paper are a secondary analysis of data originally collected in 1994. The sample included 157 decision‐making situations identified from interactions of seven triads of older home healthcare clients, their caregivers and nurses. Qualitative data were collected by participant observation and audio‐recording of admission visit interactions among clients, caregivers and nurses. Content analysis, augmented by Ethnograph software, was used to analyse the data.

Findings.  Coalitions were evident in just eight of the 157 decision‐making situations. All of the theoretically possible types of nursing care decisions (programme, operational control, agenda) were observed. Each coalition involved one nursing care decision; two coalitions formed in one triad. Seven coalitions formed between nurse and caregiver against client during two programme and five operational control decisions. One coalition formed between client and caregiver against nurse during an agenda decision. No coalitions formed between client and nurse against caregiver.

Conclusions.  Although the study sample was small, the findings expand understanding of the relation between types of decisions and formation of coalitions during triadic interactions in home health care, and provided empirical support for a portion of the Theory of Collaborative Decision‐Making in Nursing Practice for Triads.
How is the indoor environment related to asthma?: literature review
Authors: Richardson George , Eick Susan , Jones Raymond
Published: September 2005

Aims.  This paper reports a review conducted to identify the factors in the indoor environment that have an evidence‐based link with the exacerbation or development of asthma and to identify measures that healthcare professionals can promote to reduce exposure to these risk factors in the home.

Background.  The indoor environment, particularly at home, has been recognized as a major source of exposure to allergens and toxic chemicals. Exposure to allergens and toxins is thought to exacerbate respiratory conditions, in particular, asthma.

Methods.  Searches were made of health and indoor environment databases, including Cochrane Library, National Health Services Centre for Reviews and Assessment Reports, British Medical Journal, CINAHL and Ovid library, MEDSCAPE/MEDLINE, EMBASE, INGENTA, Science Citation Index, Web of Science. Searches were also made of other Internet‐based resources, including those of international and government bodies. The following keywords were used: allergens, allergen avoidance, asthma, asthma prevention, cat, damp, Der p 1, dog, environmental control, house dust mites, indoor air quality, indoor environment, meta analysis, mould, pets, remedial actions, respiratory illnesses and systematic reviews.

Findings.  There is evidence of a link between asthma and a small number of indoor environmental factors. There is currently only reasonable evidence for one causative factor for asthma in the indoor environment and that is house dust mite allergen. Although there are many studies of different remedial actions that can be taken in the home, often these give evidence of reduced risk of exposure but not clinical improvement in asthma. Although there is a lack of medical evidence for the reduction of known sensitizers such as mould, this is because of a dearth of research rather than evidence of no association.

Conclusions.  There is some evidence of a link between the indoor environment and asthma. There are measures, which could be promoted by healthcare professionals to alleviate asthmatic symptoms.
Mindfulness‐Based Stress Reduction as supportive therapy in cancer care: systematic review
Authors: Smith Joanna E. , Richardson Janet , Hoffman Caroline , Pilkington Karen
Published: September 2005

Aim.  This paper reports a systematic review and critical appraisal of the evidence on the effectiveness of Mindfulness‐Based Stress Reduction for cancer supportive care.

Background.  The experience of cancer can have a negative impact on both psychological and physical health and on quality of life. Mindfulness‐Based Stress Reduction is a therapy package that has been used with patients with a variety of conditions. In order to draw conclusions on its effectiveness for cancer patients, the evidence requires systematic assessment.

Methods.  A comprehensive search of major biomedical and specialist complementary medicine databases was conducted. Additionally, efforts were made to identify unpublished and ongoing research. Relevant research was categorized by study type and appraised according to study design. Clinical commentaries were obtained for each study and included in the review.

Results.  Three randomized controlled clinical trials and seven uncontrolled clinical trials were found. A lack of relevant qualitative research studies was identified. Studies report positive results, including improvements in mood, sleep quality and reductions in stress. A dose‐response effect has been observed between practice of Mindfulness‐Based Stress Reduction and improved outcome. A number of methodological limitations were identified. Modifications to the traditional Mindfulness‐Based Stress Reduction programme make comparison between studies difficult and a lack of controlled studies precludes any firm conclusion on efficacy.

Conclusion.  Mindfulness‐Based Stress Reduction has potential as a clinically valuable self‐administered intervention for cancer patients. Further research into its efficacy, feasibility and safety for cancer patients in the nursing context is recommended.
Advancing ophthalmic nursing practice through action research
Authors: Waterman Heather , Harker Rona , MacDonald Heather , McLaughlan Rita , Waterman Christine
Published: September 2005

Aim.  This paper reports an action research project that promoted posturing face down following macular hole surgery and aimed to enhance patient outcomes. This paper gives an overview of the process and outcomes of the first three of four phases of the project: problem identification, planning and action. The fourth phase, which was an evaluation of the project, is reported in another paper.

Background.  Surgical repair for macular hole is common procedure carried out worldwide, and patients are required to posture face down for several weeks after this surgery. There is anecdotal evidence that many patients find this difficult to carry out. In the context of increasing medical specialization, nursing practice must be developed to meet the needs of patients being treated. This study will, therefore, be relevant beyond the particular specialty and geographical location described.

Method.  The methodology was participative and cyclical. Initially, a fact‐finding exercise was undertaken, using qualitative interviews with 18 members of staff to elicit their perspectives on the posturing of patients. Based on the fact‐finding exercise, seven action objectives were set. While these were being implemented, three further research projects were identified and undertaken. Two were qualitative studies: one investigated patients’ experiences of the surgery and posturing, and the second concerned nurses’ developing working theories on the promotion of posturing and effects of nursing care on patient outcomes. Another pilot study was a randomized controlled trial to consider the effect of two different posturing regimes on patient outcomes. In addition to regular action research group meetings, these studies served to inform and monitor the changes as they were put into practice. The work was carried out from 1998 to 2002.

Findings.  Several factors appeared to influence whether patients postured after surgery, namely: education of staff and patients, appropriately timed services, clear lines of responsibility for patient care, good communication and availability of equipment.

Conclusion.  The research suggests that an approach to care is required that appreciates and deals with the multiple factors that influence whether patients carry out the posturing.
Staff in services for people with intellectual disabilities: the impact of stress on attributions of challenging behaviour
Authors: Rose D. , Rose J.
Published: October 2005

Background  There is a lack of a conceptual framework as to how stress and attribution variables interact and influence staff behaviour in response to challenging behaviour. To address this, a model is tested examining the impact of stress on attributions of challenging behaviour within Weiner's model of helping.

Method  A total of 107 staff working in community homes for people with intellectual disabilities completed a self‐report questionnaire that measured stress, burnout, attributions, emotions, optimism and helping behaviour in response to challenging behaviour.

Results  Partial support was found for the role of attributions and emotions. However, although staff reported high stress levels and moderate burnout, this did not appear to relate to their reporting of thoughts and feelings regarding challenging behaviour predicted by Weiner's helping model. It was not possible to fully test the helping model, as the ‘help’ variable was not normally distributed.

Conclusions  There was little evidence to suggest that stress has a primary role in determining staff responses when examined within Weiner's model of helping. Limited support in general was offered for Weiner's helping model. Potential conceptual difficulties and clinical implications are explored and alternative models for future research are discussed.
Bereaved adults with intellectual disabilities: a combined randomized controlled trial and qualitative study of two community‐based interventions
Authors: Dowling S. , Hubert J. , White S. , Hollins S.
Published: September 2005

Background  Bereaved adults with intellectual disabilities are known to experience prolonged and atypical grief which is often unrecognized. The aim of this project was to find an effective way to improve mental health and behavioural outcomes.

Methods  Subjects were randomized to two different therapeutic interventions: traditional counselling by volunteer bereavement counsellors, and an integrated intervention delivered by carers which offered bereavement specific support. Qualitative and quantitative methods were used to determine their effectiveness and efficacy.

Results  The counselling intervention resulted in measurable gains both clinically and in terms of quality of life; the second intervention proved impracticable in most settings and no improvement in mental health or behaviour resulted.

Conclusions  Despite small numbers, the quantitative findings were highly significant, were supported by the qualitative data, and were of practical relevance to primary care practitioners and specialist mental health and intellectual disability staff.
What am I doing in Timbuktu: person–environment picture recognition for persons with intellectual disability
Authors: Danielsson H. , Rönnberg J. , Andersson J.
Published: September 2005

Background  The aim of this study was to examine the effects of familiarity of depicted persons and environments in recognition of photographs for pupils with different degrees of intellectual disability (ID).

Method  Forty‐five pupils with ID participated.

Results  An interaction effect between the two variables, person and environment, was found in addition to main effects for both the variables. Pictures of the test person himself or herself in familiar environments were easier to recognize than in unfamiliar environments, whereas the opposite was found for pictures of other familiar persons. No interaction effects of degree of ID were found.

Conclusions  The interaction pattern is explained in terms of absent, present or implausible semantic associations between the person and the environmental context. The results are discussed in relation to augmentative and alternative communication with photographs.
Verbal communication outcomes in children with autism after in‐home father training
Authors: Seung H. K. , Ashwell S. , Elder J. H. , Valcante G.
Published: September 2005

Background  This retrospective study examined the efficacy of in‐home father training on the communicative outcomes of children with autism. The in‐home training consisted of two components: (1) expectant waiting; and (2) imitation with animation.

Methods  Efficacy of parent training was examined by measuring the ratio of utterances produced by the parents to the utterances produced by the children and the number of verbal imitation by the parents. Outcomes of the children's verbal production were examined by measuring the number of (1) single word utterances; (2) different words produced; and (3) verbal response to questions.

Results  Following training there was a decrease in the ratio of parent to child utterances and an increase in (1) the use of imitation by the parents; and (2) the number of single words and different words produced by the children.

Discussion  Results of this study suggested that the parents had learned to wait for their children to communicate verbally during communicative interactions and to interact more efficiently with their children by using verbal imitation. Overall, the results of this study support the efficacy of parent training that focuses on promotion of social reciprocity, and have important implications for clinicians and future research.
Smad Proteins are Targets of Transforming Growth Factor β1 in Immortalised Gonadotrophin‐Releasing Hormone Releasing Neurones
Authors: Galbiati M. , Saredi S. , Romanò N. , Martini L. , Motta M. , Melcangi R. C.
Published: September 2005

Transforming growth factor β (TGFβ) is one of the growth factors involved in the neuroendocrine control of the gonadotrophin‐releasing hormone (GnRH) neurones. It is produced and released by the astrocytes surrounding GnRH neurones and directly controls their secretory activity. TGFβ signalling is based on a complex of two receptors that transduces the signal through peculiar intracellular substrates, the Smad proteins, which, upon activation, move into the nucleus, and modify the transcription of TGFβ responsive genes. The present study aimed to verify whether TGFβ1 is able to regulate the Smad pathway in GT1‐1 cells (i.e. an immortalised neuronal cell line releasing GnRH). We show that: (i) GT1‐1 cells express Smad 2, 3, 4, and 7; (ii) TGFβ1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15–30 min); (iii) TGFβ1 induces the synthesis of the inhibitory Smad 7 at longer times (60–120–240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1‐1 cells and a TGFβ1 neutralising antibody counteracts this effect. The results indicate that Smads are targets of TGFβ1 and that astrocytes are able to modulate Smads proteins in GT1‐1 cells through the release of TGFβ1. Taken together, the data provide new evidence that glial cells are important regulators of the GnRH neuronal activity.
Pituitary‐Adrenal Responses to Cholinergic Stimulation and Acute Mild Stress are Differentially Elevated in Male and Female M2Muscarinic Receptor Knockout Mice
Authors: Rhodes M. E. , Billings T. E. , Czambel R. K. , Rubin R. T.
Published: October 2005

Adrenocorticotrophic hormone (ACTH) and corticosterone responses to cholinergic stimulation are greater in male rats and mice than in females. To explore the role of M2muscarinic receptors in this sex difference, we administered the nonselective muscarinic agonist, oxotremorine, the acetylcholinesterase inhibitor, physostigmine, and saline (a mild stressor) to male and female M2receptor knockout (KO) and wild‐type (WT) mice of the same genetic background. Because M2receptors function primarily as presynaptic autoreceptors, we hypothesized that their absence in M2KO mice would increase the sensitivity of hormone responses to cholinergic stimulation in these groups. Both male and female M2KO mice were significantly more responsive to the stress of saline injection than were their WT counterparts. Oxotremorine and physostigmine increased ACTH and corticosterone in all four groups, but to a significantly greater degree in KO males compared to WT males, KO females, and WT females. The increase in ACTH also was significantly greater in WT males compared to WT females. By contrast, the increase in corticosterone was significantly more in females compared to males, independent of genotype. Following pretreatment with the nonselective muscarinic antagonist, scopolamine, ACTH and corticosterone responses to oxotremorine and to saline in the M2KO mice were comparable with those of their WT counterparts. These findings suggest that the M2muscarinic receptor subtype influences male and female pituitary‐adrenal responses following stimulation by both mild stress and cholinergic drugs. The M2receptor appears to regulate ACTH responses to cholinergic stimulation in males but not in females; however, other muscarinic receptors may be involved because corticosterone responses were higher in females compared to males. Because ACTH and corticosterone responses were greater in male and female M2KO mice, the M2receptor appears to dampen the stress response.
Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication
Authors: Yang J. , Bo X. C. , Ding X. R. , Dai J. M. , Zhang M. L. , Wang X. H. , Wang S. Q.
Published: September 2005

Summary.  Chronic hepatitis B virus (HBV) infection is a major worldwide public health problem. Better therapeutics and treatment strategies are urgently needed because of ineffective clinical treatment. Our previous study showed that asialoglycoprotein receptor 1 (ASGPR1) was upregulated by HBV but downregulated by lamivudine in HepG2.2.15 cells. It has also been reported that ASGPR is a candidate receptor for HBV attachment to hepatocytes. Therefore, as a major subunit of ASGPR, ASGPR1, might be a potential target for anti‐HBV drugs. To validate this hypothesis, antisense oligonucleiotides (ASODNs) were used to downregulate ASGPR1 level in HepG2.2.15 cells. By using the MFOLD web server and BLAST searches, five ASODNs theoretically targeting ASGPR1 were selected. After 72 h post‐transfection, HBV‐DNA level in cell medium were examined by real‐time polymerase chain reaction (PCR). Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were detected using enzyme‐linked immunosorbent assay (ELISA). ASGPR1 mRNA and protein level were measured by semi‐quantitative reverse transcriptase (RT)‐PCR and Western blot analysis respectively. The results showed that ASODN2 significantly downregulated ASGPR1 level. It also reduced HBV‐DNA, HBsAg and HBeAg level in cell medium as observed with lamivudine. In contrast, the sense sequence and scrambled sequence of ASODN2 had no effect on ASGPR1 and HBV markers in HepG2.2.15 cells. This indicated that ASODN2 could specifically reduce HBV replication in vitro. Additionally, cell proliferation and apoptosis assay suggested that downregulation of ASGPR1 did not affect cell viability. We, therefore, proposed that ASODNs targeted against ASGPR1 could block HBV replication without the influence of other changes, and ASGPR1 could be targeted for anti‐HBV drug development.
Requirements for chemotaxis protein localization in Rhodobacter sphaeroides
Authors: Wadhams George H. , Martin Angela C. , Warren Anna V. , Armitage Judith P.
Published: September 2005

Many proteins have recently been shown to localize to different regions of the bacterial cell. This is most striking in the case of the Escherichia coli chemotaxis pathway in which the components localize at the cell poles. Rhodobacter sphaeroides has a more complex chemotaxis system with two complete pathways, each localizing to different positions, one pathway at the pole and one at a discrete cluster within the cytoplasm of the bacterium. Using genomic replacement of the wild‐type chemotaxis genes in R. sphaeroides with their corresponding fluorescent protein fusions in conjunction with in frame deletions of other chemotaxis genes, we have investigated which proteins are required for the formation of the polar and cytoplasmic chemotaxis protein clusters. As in E. coli, the polarly targeted CheA and CheW homologues are required for the formation of the polar cluster. However, the formation of the cytoplasmic cluster requires the cytoplasmic chemoreceptors and CheW but not the CheAs. Interestingly, even when deletion of a component resulted in the chemotaxis proteins of one pathway becoming delocalized and diffuse in the cytoplasm, in no case were any chemotaxis proteins seen to localize to the other signalling cluster.
AIP56, a novel plasmid‐encoded virulence factor of Photobacterium damselae subsp. piscicida with apoptogenic activity against sea bass macrophages and neutrophils
Authors: do Vale Ana , Silva Manuel T. , dos Santos Nuno M. S. , Nascimento Diana S. , Reis‐Rodrigues Pedro , Costa‐Ramos Carolina , Ellis Anthony E. , Azevedo Jorge E.
Published: September 2005

A strategy used by extracellular pathogens to evade phagocytosis is the utilization of exotoxins that kill host phagocytes. We have recently shown that one major pathogenicity strategy of Photobacterium damselae subsp. piscicida (Phdp), the agent of the widespread fish pasteurellosis, is the induction of extensive apoptosis of sea bass macrophages and neutrophils that results in lysis of these phagocytes by post‐apoptotic secondary necrosis. Here we show that this unique process is mediated by a novel plasmid‐encoded apoptosis inducing protein of 56 kDa (AIP56), an exotoxin abundantly secreted by all virulent, but not avirulent, Phdp strains tested. AIP56 is related to an unknown protein of the enterohemorrhagic Escherichia coli O157:H7 and NleC, a Citrobacter rodentium type III secreted effector of unknown function. Passive immunization of sea bass with a rabbit anti‐AIP56 serum conferred protection against Phdp challenge, indicating that AIP56 represents a key virulence factor of that pathogen and is a candidate for the design of an anti‐pasteurellosis vaccine.
p75NTR independent oligodendrocyte death in cuprizone‐induced demyelination in C57BL/6 mice
Authors: Copray J. C. V. M. , Küst B. M. , Mantingh‐Otter I. , Boddeke H. W. G. M.
Published: October 2005

Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T‐lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75NTR, a ‘stress‐receptor’ which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75NTR in the fate of oligodendrocytes, we have exposed wild‐type as well as p75NTR‐knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75NTR did not alter cuprizone‐induced oligodendrocyte death (and subsequent de‐ or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75NTR activated signal transduction in the absence of T‐lymphocytes and T‐lymphocyte derived cytokines.
Contributors to white matter damage in the frontal lobe in Alzheimer's disease
Authors: Chalmers K. , Wilcock G. , Love S
Published: October 2005

Abnormalities of cerebral white matter are present in a majority of patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction and cognitive impairment. The white matter abnormalities are usually attributed to degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In the present study we examined sections of frontal lobe from 125 autopsy‐confirmed cases of AD and assessed the relationship of degenerative large and small vessel disease, CAA, parenchymal Aβ load and APOE genotype, to several objective measures of white matter damage: extent of immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation of amyloid precursor protein (APP), axon density in superficial and deep white matter, and intensity of staining for myelin. We found no association between atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter damage. However, labelling of white matter for GFAP correlated strongly with the parenchymal Aβ load (P = 0.0003) and with APP accumulation (P = 0.008). Our findings suggest that severity of frontal white matter damage in AD is closely related to parenchymal Aβ load and that in most cases the contribution of degenerative vascular disease, CAA and APOE is relatively minor.
Phenotypic variability in human prion diseases
Authors: Ironside J. W. , Ritchie D. L. , Head M. W.
Published: October 2005

Human prion diseases are rare neurodegenerative disorders that can occur as sporadic, familial or acquired disorders. Within each of these categories there is a wide range of phenotypic variation that is not encountered in other neurodegenerative disorders. The identification of the prion protein and its key role in the pathogenesis of this diverse group of diseases has allowed a fuller understanding of factors that influence disease phenotype. In particular, the naturally occurring polymorphism at codon 129 in the prion protein gene has a major influence on the disease phenotype in sporadic, familial and acquired prion diseases, although the underlying mechanisms remain unclear. Recent technical advances have improved our ability to study the isoforms of the abnormal prion protein in the brain and in other tissues. This has lead to the concept of molecular strain typing, in which different isoforms of the prion protein are proposed to correspond to individual strains of the transmissible agent, each with specific biological properties. In sporadic Creutzfeldt‐Jakob disease there are at least six major combinations of codon 129 genotype and prion protein isotype, which appear to relate to distinctive clinical subgroups of this disease. However, these relationships are proving to be more complex than first considered, particularly in cases with more than a single prion protein isotype in the brain. Further work is required to clarify these relationships and to explain the mechanism of neuropathological targeting of specific brain regions, which accounts for the diversity of clinical features within human prion diseases.
SUMOylation substrates in neuronal intranuclear inclusion disease
Authors: Takahashi‐Fujigasaki J. , Arai K. , Funata N. , Fujigasaki H.
Published: October 2005

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized pathologically by the presence of ubiquitinated intranuclear inclusions (NII) in neuronal cells. We demonstrate that NIIs in both sporadic and familial NIID contained the small ubiquitin modifier‐1 (SUMO‐1) and the SUMOylation substrates promyelocytic leukaemia protein (PML) and histone deacetylase 4 (HDAC4). Both PML and SUMO‐1 are major components of nuclear bodies (NBs), suggesting that the NIIs in NIID, as well as the intranuclear inclusions in polyglutamine diseases, might derive from these intranuclear functional domains that serve as sites for ubiquitin‐related protein degradation. HDAC4 was also a major component of the NIIs. HDACs are transcriptional corepressors that regulate histone remodelling, and NBs are thought to be sites at which the level of histone acetylation is controlled. The presence of PML, SUMO‐1 and HDAC4 in NIIs suggests that transcriptional activity regulated by histone acetylation might contribute to the disease process in NIID. In addition, we showed that another SUMOylation substrate, RanGAP1 is associated with NIIs only in the familial NIID patient. This might be explained by different pathogenetic mechanisms underlying subcategories of NIID, which is very heterogeneous.