Nurses' needs when collaborating with other healthcare professionals in palliative dementia care.

Adequate interprofessional collaboration is essential to provide high quality palliative dementia care across different settings. Within interprofessional collaboration, nurses are the frontline healthcare professionals (HCPs), who interact closely with people with dementia, their loved ones, and other HCPs. A survey was conducted to explore the needs of nurses regarding interprofessional collaboration in home care (HC) organisations, nursing homes (NHs) and during NH admissions. The survey identified the perceived quality of and preferred needs regarding interprofessional collaboration. In total, 384 participants (53.9% home care nurses) completed the survey. The most frequently reported collaboration needs in HC organisations and NH were optimal communication content e.g. information transfer and short communication lines (being able to easily contact other disciplines), and coordination e.g. one contact person, and clear task division and responsibilities). During NH admissions, it was important to create transparency about agreements concerning end-of-life wishes, optimize nurse-to-nurse handover during NH admissions (through performing visits prior to admissions, and receiving practical information on how to guide relatives), and improve coordination (e.g. one contact person). In conclusion, the key collaboration needs were organising central coordination, establishing optimal communication, and creating transparency on end-of-life care agreements.

Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks.

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any 'gold standard'. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.

Field vaccinated chickens with low antibody titres show equally insufficient protection against matching and non-matching genotypes of virulent Newcastle disease virus.

Newcastle disease (ND) is a severe threat to the poultry industry and is caused by virulent strains of Newcastle disease virus (NDV). Many countries maintain a vaccination policy, but NDV is rapidly evolving as shown by the discovery of several new genotypes in the last decades. We tested the efficacy of the currently used classical commercial ND vaccine based on the genotype II strain VG/GA, applied under standard field conditions, against outbreak strains. Field vaccinated broilers were challenged with four different viruses belonging to genotype II, V or VII. A large proportion of field vaccinated broilers showed suboptimal immunity and the protection level against early and recent NDV isolates was dramatically low. Furthermore, there were no significant differences in protection afforded by a genotype II vaccine against a genotype II virus challenge compared to a challenge with viruses belonging to the other genotypes. This study suggests that the susceptibility of vaccinated poultry to NDV infection is not the result of vaccine mismatch, but rather of poor vaccination practices.

Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment.

The aim of the study was to investigate prospectively the prevalence of testosterone deficiency (TD) in patients with testicular germ-cell cancer (TGCC) using longitudinal data. A total of 376 TGCC patients were evaluated for serum testosterone levels before, during and after the following therapies: cisplatin-based polychemotherapy, carboplatin monotherapy, radiotherapy or surgery only. Complete serial hormone analyses were performed on 160 patients (age: 33.8±9.1years, mean±SD). All patients received treatment according to the guidelines of the 'German Testicular Cancer Study Group' and the 'European Germ Cell Cancer Consensus Group' or within studies performed by the 'European Organisation for Research and Treatment of Cancer' and the 'Deutsche Krebsgesellschaft'. Main outcome measurements were sexual hormone profiles over time. Statistical analysis of 1831 testosterone serum levels over time revealed a persistent TD in 23.9% of seminoma and 26.2% of non-seminoma patients. TD was associated with subnormal residual testicular volumes (<12mL). In conclusion, TD rates are high in testis cancer patients. This is present at primary diagnosis and most likely related to testicular dysgenesis or atrophy. Our longitudinal evaluation indicates that treatment modalities have minor influence and effect on the persistently high rates of TD in TGCC patients.

Highly diverse variable number tandem repeat loci in the E. coli O157:H7 and O55:H7 genomes for high-resolution molecular typing.

AIM: Evaluation of the Escherichia coli genome for variable number tandem repeat (VNTR) loci in order to provide a subtyping tool with greater discrimination and more efficient capacity. METHODS AND RESULTS: Twenty-nine putative VNTR loci were identified from the E. coli genomic sequence. Their variability was validated by characterizing the number of repeats at each locus in a set of 56 E. coli O157:H7/HN and O55:H7 isolates. An optimized multiplex assay system was developed to facility high capacity analysis. Locus diversity values ranged from 0.23 to 0.95 while the number of alleles ranged from two to 29. This multiple-locus VNTR analysis (MLVA) data was used to describe genetic relationships among these isolates and was compared with PFGE (pulse field gel electrophoresis) data from a subset of the same strains. Genetic similarity values were highly correlated between the two approaches, through MLVA was capable of discrimination amongst closely related isolates when PFGE similar values were equal to 1.0. CONCLUSIONS: Highly variable VNTR loci exist in the E. coli O157:H7 genome and are excellent estimators of genetic relationships, in particular for closely related isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli O157:H7 MLVA offers a complimentary analysis to the more traditional PFGE approach. Application of MLVA to an outbreak cluster could generate superior molecular epidemiology and result in a more effective public health response.

Factors associated with residual breast cancer after re-excision for close or positive margins.

BACKGROUND: Successful breast conservation surgery (BCS) requires complete tumor excision. Margin status of the initial specimen determines the need for additional surgery. We explored factors associated with residual cancer (RC) upon follow-up surgery in patients with close, positive, or undetermined margins following BCS. METHODS: A retrospective analysis of 276 patients with initial close, positive, or undetermined margins who underwent re-excision (RE) or mastectomy was conducted. All initial excisions were intended as definitive procedures. Chi-square analysis was used to identify factors that may predict RC. RESULTS: Of 276 patients, 87 had close, 168 had positive, and 21 had undetermined margins on initial excision. Of this group, 63% (175/276) had RC upon RE or mastectomy. Of positive-margin patients, 68% had RC, compared with 53% of close-margin and 67% of undetermined-margin patients (P = .006). Tumors >/=2 cm were more often associated with RC than smaller tumors (70.8% vs. 56.5%; P = .07). This association was strongest in positive-margin patients (P = .04). High tumor grade was associated with RC in all groups. RC linearly increased with the number of involved margins (P = .02). Specimen inking with multiple colors was associated with decreased risk of RC (P = .004). CONCLUSIONS: Over half of patients with involved or undetermined margins had RC upon RE or mastectomy. Positive and undetermined margins were more often associated with RC than close margins. Larger tumor size was associated with RC in patients with positive. Increasing tumor grade suggests a greater chance of detecting RC in all groups. Multiple involved margins led to a greater risk of RC.

Establishment of a recombinant expression system for connective tissue growth factor (CTGF) that models CTGF processing in utero.

Connective tissue growth factor (CTGF) stimulates cell proliferation, migration, adhesion and extracellular matrix production, and functions in processes such as development, differentiation, angiogenesis, implantation, wound healing and fibrosis. CTGF is a 38 kDa protein that comprises four discrete structural modules (modules 1-4) but is susceptible to limited proteolysis in utero yielding bioactive isoforms that comprise either modules 3 and 4 (16-20 kDa) or module 4 (10 kDa). Here we report the development of a stable cell line, termed DB1, that was generated by transfecting cDNA encoding full-length human CTGF into Chinese hamster ovary cells that were mutant for heparin sulphate and chondroitin sulphate. DB1 cells produced 38 kDa CTGF and low molecular mass CTGFs that had N-termini between modules 2 and 3 at Ala(181) (20 kDa), Leu(184) (18 kDa) or Ala(197) (16 kDa) or between modules 3 and 4 at Gly(253) (10 kDa). CTGF was exported from DB1 cells as early as 5 min after synthesis and all isoforms were readily purified from conditioned medium by sequential steps of heparin affinity, cation exchange, and reverse-phase chromatography. The 38 kDa CTGF was faithfully glycosylated and underwent limited proteolysis in the presence of thrombin, kallikrein or uterine fluids, the last of which was antagonized by anti-thrombin III. All CTGF isoforms promoted cell adhesion, mitosis and epithelial transdifferentiation in vitro as well as subcutaneous fibrosis in vivo. The establishment of this recombinant expression system allows for mass-scale production of all previously reported uterine CTGF isoforms, demonstrates that module 4 contains functional domains involved in a broad range of biological activities, and will facilitate studies of CTGF processing in vitro.

The heparin-binding 10 kDa fragment of connective tissue growth factor (CTGF) containing module 4 alone stimulates cell adhesion.

Connective tissue growth factor (CTGF) is a 349-residue mosaic protein that contains four structural modules implicated in protein-protein interactions. To address the functionality of residues 247-349 (containing module 4 alone), this region of CTGF was produced as a maltose binding protein (MBP) fusion protein in E. coli. After removal of MBP, recombinant CTGF commenced at Glu(247), was of M(r) 10 000, was immunoreactive with anti-CTGF[247-260], bound strongly to heparin, and promoted dose-dependent adhesion of fibroblasts, myofibroblasts, endothelial cells, and epithelial cells. An 8 kDa presumptive C-terminally truncated form of CTGF commencing at Glu(247) also promoted cell adhesion. CTGF-mediated cell adhesion was abolished by heparin or EDTA. These data demonstrate the presence of heparin-binding and cell-adhesion motifs within the C-terminal 103 residues of CTGF and show that CTGF-mediated cell adhesion is heparin-and divalent cation-dependent. Thus, CTGF isoforms comprising essentially module 4 are intrinsically functional in the absence of the other constituent modules of CTGF.

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men.

OBJECTIVE: In a phase I single-centre, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers. DESIGN: To eliminate the influence of endogenous serum testosterone, gonadotrophins and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied. RESULTS: In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone. CONCLUSION: Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.

Age differences in implicit and explicit associative memory: exploring elaborative processing effects.

Research in memory processes suggests implicit memory is more resistant to the effects of aging than explicit memory. Two experiments examined how variations in level of processing affect memory for novel word-pair associations across age groups. The results indicate that new learning may rely on some degree of elàborate and even explicit processing and that older adults show deficits in any form of new learning. Explicit associative memory benefited from elaborative processing for both age groups and age differences appeared to relate to overall working-memory capacity rather than effective use of elaborative processes. These results support a model of associative memory that distinguishes automatic unconscious processes versus conscious controlled processes in which older adults exhibit deficits in associative memory tasks that actually rely on consciously controlled processes.

Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells.

Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We show here that insulin activates the transcription of its own gene and that of the beta cell glucokinase gene (betaGK) by different mechanisms. Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the betaGK gene by signaling via insulin receptor B type (Ex11+), PI3K class II-like activity, and PKB (c-Akt). Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases.

Language decline across the life span: findings from the Nun Study.

The present study examines language samples from the Nun Study. Measures of grammatical complexity and idea density were obtained from autobiographies written over a 60-year span. Participants who had met criteria for dementia were contrasted with those who did not. Grammatical complexity initially averaged 4.78 (on a 0-to-7-point scale) for participants who did not meet criteria for dementia and declined .04 units per year; grammatical complexity for participants who met criteria for dementia initially averaged 3.86 and declined .03 units per year. Idea density averaged 5.35 propositions per 10 words initially for participants who did not meet criteria for dementia and declined an average of .03 units per year, whereas idea density averaged 4.34 propositions per 10 words initially for participants who met criteria for dementia and declined .02 units per year. Adult experiences, in general, did not moderate these declines.

The structure of verbal abilities in young and older adults.

Four language sample measures as well as measures of vocabulary, verbal fluency, and memory span were obtained from a sample of young adults and a sample of older adults. Factor analysis was used to analyze the structure of the vocabulary, fluency, and span measures for each age group. Then an "extension" analysis was performed by using structural modeling techniques to determine how the language sample measures were related to the other measures. The measure of grammatical complexity was associated with measures of working memory including reading span and digit span. Two measures, sentence length in words and a measure of lexical diversity, were associated with the vocabulary measures. The fourth measure, propositional density, was associated with the fluency measures as a measure of processing efficiency. The structure of verbal abilities in young and older adults is somewhat different, suggesting age differences in processing efficiency.

Cognitive construct measurement in small samples of younger and older adults: an example of verbal working memory.

An important issue in experimental aging research is the accurate measurement of cognitive constructs, particularly in small-sample studies. Latent variable modeling approaches to assessing age-based construct similarity are difficult to implement in smaller-scale studies, which tend to have small samples and measurement of a single construct. We discuss factor score comparison methods for assessing age-based construct similarity that may be more appropriate for small-scale studies. We then examine these methods for a series of single-factor models of verbal working memory (VWM) based on data from three separate studies in which small samples of younger and older adults' completed VWM-based tasks. Our single-factor models accounted well for the associations among the sets of VWM tasks. This construct was also measured well across age groups and different samples. Our analyses suggest that factor score comparison methods may be useful for small-scale studies that require assessment of age-based measurement similarity in cognitive constructs.

Longitudinal change in language production: effects of aging and dementia on grammatical complexity and propositional content.

Mixed modeling was used to examine longitudinal changes in linguistic ability in healthy older adults and older adults with dementia. Language samples, vocabulary scores, and digit span scores were collected annually from healthy older adults and semiannually from older adults with dementia. The language samples were scored for grammatical complexity and propositional content. For the healthy group, age-related declines in grammatical complexity and propositional content were observed. The declines were most rapid in the mid 70s. For the group with dementia, grammatical complexity and propositional content also declined over time, regardless of age. Rates of decline were uniform across individuals. These analyses reveal how both grammatical complexity and propositional content are related to late-life changes in cognition in healthy older adults aswell as those with dementia. Alzheimer's disease accelerates this decline, regardless of age.

Secreted euryarchaeal microhalocins kill hyperthermophilic crenarchaea.

Few antibiotics targeting members of the archaeal domain are currently available for genetic studies. Since bacterial antibiotics are frequently directed against competing and related organisms, archaea by analogy might produce effective antiarchaeal antibiotics. Peptide antibiotic (halocin) preparations from euryarchaeal halophilic strains S8a, GN101, and TuA4 were found to be toxic for members of the hyperthermophilic crenarchaeal genus Sulfolobus. No toxicity was evident against representative bacteria or eukarya. Halocin S8 (strain S8a) and halocin R1 (strain GN101) preparations were cytostatic, while halocin A4 (strain TuA4) preparations were cytocidal. Subsequent studies focused on the use of halocin A4 preparations and Sulfolobus solfataricus. Strain TuA4 cell lysates were not toxic for S. solfataricus, and protease (but not nuclease) treatment of the halocin A4 preparation inactivated toxicity, indicating that the A4 toxic factor must be a secreted protein. Potassium chloride supplementation of the Sulfolobus assay medium potentiated toxicity, implicating use of a salt-dependent mechanism. The utility of halocin A4 preparations for genetic manipulation of S. solfataricus was assessed through the isolation of UV-induced resistant mutants. The mutants exhibited stable phenotypes and were placed into distinct classes based on their levels of resistance.

Sentence repetition and processing resources in Alzheimer's disease.

Sentence processing in Alzheimer's disease (AD) has been found to be influenced by several grammatical and extragrammatical factors, including phrase structure and verb-argument relations, number of propositions/verbs, and processing resource capacity. This study examines the effects of these variables on sentence production in AD. Normal control and AD subjects were asked to repeat six types of sentences varying along the above dimensions of complexity. Subjects' processing resource capacity was measured using several verbal working memory tests. AD subjects' sentence-repetition performance was impaired compared to the normal control group. Significant effects were observed for branching direction of phrase structure, canonicity of verb-argument relations, and serial position of errors. Sentence-repetition performance significantly correlated with working memory scores. The findings are interpreted within a resource capacity theory of sentence processing.

Dose-response effects of inactivated Newcastle disease vaccines: influence of serologic assay, time after vaccination, and type of chickens.

Knowledge of the dose-response relation of inactivated vaccines and of the factors that influence this relation is essential for the evaluation of existing vaccine potency assays and the development of new potency assays that are based on the antigen content of the inactivated vaccines. We quantified the relation between vaccine dose, serologic response, and clinical protection after vaccination for three different inactivated Newcastle disease (ND) vaccines. Qualitatively, similar dose-response curves were obtained for the three vaccines when either the serologic response or the clinical protection of specific-pathogen-free (SPF) chickens was plotted against the different vaccine doses applied. However, the vaccines differed quantitatively: doses of vaccines that induced similar antibody titers or clinical protection differed 2-8-fold. In contrast with the narrow range of antibody titers induced by a full vaccine dose, a very broad range of titers was obtained after dilution of the vaccines. At least 95% of the SPF chickens with detectable antibody in the serum were protected against a challenge with virulent Herts ND virus. The relation between the dosage of two different ND vaccines and the serum antibody titers remained markedly constant between 3 and 18 wk after vaccination. Vaccination of broilers instead of layers with a dilution series of inactivated ND vaccine resulted in significantly lower antibody levels and less clinical protection against virulent challenge. In conclusion, despite quantitative differences, we found comparable dose-response relations for the three inactivated ND vaccines studied.

Experimentally disentangling what's beneficial about elderspeak from what's not.

Three studies evaluated different varieties of elderspeak using a referential communication task. Experiment 1 compared the effects of syntactic simplifications and semantic elaborations. Experiment 2 contrasted syntactic simplifications and prosodic exaggerations. Experiment 3 contrasted 2 different syntactic simplification strategies and 2 different prosodic exaggerations. Providing semantic elaborations and reducing the use of subordinate and embedded clauses benefit older adults and improve their performance on the referential communication task, whereas reducing sentence length, slowing speaking rate, and using high pitch do not. The use of short sentences, a slow rate of speaking, and high pitch resulted in older adults' reporting more communication problems. These experiments validate a version of elderspeak that benefits older adults without sounding patronizing and insulting.

Aging and resolution of quantifier scope effects.

Two experiments were conducted to compare young and older adults' processing of complex sentences involving quantifier scope ambiguities. Young adults were hypothesized to use a mix of syntactic processing strategies to interpret sentences such as Every actor used a prop or An actor used every prop. Older adults, particularly those with limited working memories, were hypothesized to rely on a simple pragmatic principle. Participants read the quantifier sentences and judged whether a continuation sentence "made sense." Reading times for the quantifier sentences and decision times and continuation sentence acceptability judgements were analyzed. Whereas young and older adults exhibited similar patterns of reading times for the quantifier sentences, they preferred different continuations for the Every ... a quantifier sentences. As predicted, both young adults and older adults interpreted a quantifier sentence such as An actor used every prop as referring to a single entity resulting in a preference for continuations such as The actor was on the stage. In contrast, young and older adults made different interpretations of a quantifier sentence such as Every actor used a prop; young adults preferred continuations postulating multiple entities such as The props were on the stage whereas older adults, particularly those with working memory limitations, preferred continuations with a single entity such as The prop was on the stage. These results support models of the effects of aging on language processing in which immediate syntactic analysis is not affected by aging or working memory limitations whereas postcomprehension processes are affected by aging and/or working memory limitations.