Marital status, quality of life, and clinical outcome in patients with heart failure

AIM: This study investigated the impact of having a partner on quality of life (QoL), the number of hospital readmissions, and 9-month survival in patients with heart failure (HF). METHODS: The study population consisted of hospitalized patients with HF. QoL was measured by the Cantril Ladder of Life (0-10) during hospital admission. Clinical data, readmission rate, and number of deaths were registered by patient interview and chart review. RESULTS: Of the 179 patients, 96 (54%) were married or were living with a partner. Differences in QoL between married patients and those living alone were most pronounced with regard to future expectations of QoL (6.5 vs 5.0, P=.00). However, in a multivariate model QoL was primarily associated with socioeconomic status, age, and gender. Married patients had 12% less events in the 9-month follow-up period compared with patients living alone (P=not significant). CONCLUSION: This study indicates that most patients with HF who are living alone are mostly elderly women with a low socioeconomic status, who are at risk for recurrent events and a worse QoL.     

Fluorine‐18 labelling of a series of potential EGFRvIII targeting peptides with a parallel labelling approach using [18F]FPyME

There is growing interest in the use of radiolabelled peptides as receptor targeting agents for diagnostic imaging of various cancer types using positron emission tomography. In this work, 1‐[3‐(2‐[¹⁸F]fluoropyridin‐3‐yloxy)propyl]pyrrole‐2,5‐dione ([¹⁸F]FPyME) has been used for parallel fluorine‐18 labelling of PEPHC1, a peptide selective towards the cancer‐specific mutation of the epidermal growth factor receptor (EGFRvIII), and a number of truncated and mutated analogues. Conjugation of the peptides with [¹⁸F]FPyME was achieved within 10 min in non‐decay‐corrected radiochemical yields of 30–50%. The high yield of the conjugation reaction combined with its short synthesis time allows the labelling of several peptides from a single batch of [¹⁸F]FPyME. Copyright © 2010 John Wiley & Sons, Ltd.     

Fasciola hepatica expresses multiple alpha- and beta-tubulin isotypes

We have identified five alpha-tubulin and six beta-tubulin isotypes that are expressed in adult Fasciola hepatica. Amino acid sequence identities ranged between 72 and 95% for fluke alpha-tubulin and between 65 and 97% for beta-tubulin isotypes. Nucleotide sequence identity ranged between 68-77% and 62-80%, respectively, for their coding sequences. Phylogenetic analysis indicated that two of the alpha-tubulins and two of the beta-tubulins were distinctly divergent from the other trematode and nematode tubulin sequences described in this study, whereas the other isotypes segregated within the trematode clades. With regard to the proposed benzimidazole binding site on beta-tubulin, three of the fluke isotypes had tyrosine at position 200 of beta-tubulin, two had phenylalanine and one had leucine. All had phenylalanine at position 167 and glutamic acid at position 198. When isotype RT-PCR fragment sequences were compared between six individual flukes from the susceptible Cullompton isolate and from seven individual flukes from the two resistant isolates, Sligo and Oberon, these residues were conserved.     

c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains

Many bacterial pathogens inject into host cells effector proteins that are substrates for host tyrosine kinases such as Src and Abl family kinases. Phosphorylated effectors eventually subvert host cell signaling, aiding disease development. In the case of the gastric pathogen Helicobacter pylori, which is a major risk factor for the development of gastric cancer, the only known effector protein injected into host cells is the oncoprotein CagA. Here, we followed the hierarchic tyrosine phosphorylation of H. pylori CagA as a model system to study early effector phosphorylation processes. Translocated CagA is phosphorylated on Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs EPIYA-A, EPIYA-B, and EPIYA-C in Western strains of H. pylori and EPIYA-A, EPIYA-B, and EPIYA-D in East Asian strains. We found that c-Src only phosphorylated EPIYA-C and EPIYA-D, whereas c-Abl phosphorylated EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D. Further analysis revealed that CagA molecules were phosphorylated on 1 or 2 EPIYA motifs, but never simultaneously on 3 motifs. Furthermore, none of the phosphorylated EPIYA motifs alone was sufficient for inducing AGS cell scattering and elongation. The preferred combination of phosphorylated EPIYA motifs in Western strains was EPIYA-A and EPIYA-C, either across 2 CagA molecules or simultaneously on 1. Our study thus identifies a tightly regulated hierarchic phosphorylation model for CagA starting at EPIYA-C/D, followed by phosphorylation of EPIYA-A or EPIYA-B. These results provide insight for clinical H. pylori typing and clarify the role of phosphorylated bacterial effector proteins in pathogenesis.     

The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation

Local control of mRNA translation has been proposed as a mechanism for regulating synapse-specific plasticity associated with long-term memory. We show here that glomerulus-selective plasticity of Drosophila multiglomerular local interneurons observed during long-term olfactory habituation (LTH) requires the Ataxin-2 protein (Atx2) to function in uniglomerular projection neurons (PNs) postsynaptic to local interneurons (LNs). PN-selective knockdown of Atx2 selectively blocks LTH to odorants to which the PN responds and in addition selectively blocks LTH-associated structural and functional plasticity in odorant-responsive glomeruli. Atx2 has been shown previously to bind DEAD box helicases of the Me31B family, proteins associated with Argonaute (Ago) and microRNA (miRNA) function. Robust transdominant interactions of atx2 with me31B and ago1 indicate that Atx2 functions with miRNA-pathway components for LTH and associated synaptic plasticity. Further direct experiments show that Atx2 is required for miRNA-mediated repression of several translational reporters in vivo. Together, these observations (i) show that Atx2 and miRNA components regulate synapse-specific long-term plasticity in vivo; (ii) identify Atx2 as a component of the miRNA pathway; and (iii) provide insight into the biological function of Atx2 that is of potential relevance to spinocerebellar ataxia and neurodegenerative disease.     

Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145

Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity.

Methods

The approach was used for [¹¹C]SB207145, a new PET radioligand for imaging the cerebral 5-HT₄ receptors in humans. Test–retest PET studies with varying specific activities of [¹¹C]SB207145 were conducted in seven healthy subjects, and the output parameter regional BP_ND was modeled. Individual occupancy plots were first computed to estimate the mass dose that saturates 50% of receptors (ID₅₀), and subsequently, the maximal mass dose that can be injected (arbitrarily set at an occupancy <5%) was calculated. Scatchard plots were computed to estimate the in vivo K_D.

Results

Increasing the mass dose resulted in a decrease in BP_ND, whilst the relative cerebellar uptake was unchanged. The ID₅₀ was 85.4±30.2 μg, and the upper mass dose limit was 4.5±1.6 μg, which does not require ultrahigh specific activity. The estimated in vivo K_D was 2.8 nM (range 1.0–4.8), without any regional differences.

Conclusion

The presented method for estimating the upper mass dose limit is suggested as part of validation of PET radioligands.     

Victims of Bullying Among Students With a Disability or Chronic Illness and Their Peers: A Cross-National Study Between Ireland and France

PurposeTo explore bullying victimization among French and Irish students with a disability or chronic illness (D/CI), considering individual, social, and family factors. We investigated this issue in France and Ireland because of the documented differences between these two countries on relevant contextual factors.MethodsData from 12,048 students aged 11, 13, and 15 years (50.1% were boys) as part of the cross-national study 2006 Health Behaviour in School-aged Children were analyzed. Self-completion questionnaires were administered in classrooms; information on socio-demographic characteristics, bullying involvement, D/CI, school participation, social network, and family were collected. Multivariate logistic regressions were performed with individual, social, and family cofactors.ResultsOverall, the prevalence of bullying victimization was significantly higher in France compared with Ireland (34.2% [33.1–35.5] and 25.9% [24.5–27.4, respectively]). Youngest were more likely to report victimization; however, no gender differences were observed. In both countries, students with D/CI were significantly more likely to report that they have been bullied compared with students without D/CI, and a significant additional risk of being bullied was found when students reported D/CI with restriction in school participation. Regardless of country and D/CI status, being bullied was significantly associated with weaker social support and difficulty of communication with fathers, with even stronger associations found among students with D/CI.ConclusionAdolescents with D/CI are more likely to be victimized than their peers, with a similar risk in both countries. Besides individual, social and family factors are consistently associated to bullying victimization across countries. These results will guide future antibullying prevention programs.