How Greek nurses perceive and overcome the barriers in implementing treatment for pressure ulcers: 'against the odds'.

OBJECTIVE: Although the occurrence of pressure ulcers (PUs) is now considered as an indicator of poor quality nursing care, questions and concerns remain regarding situations where PUs were unavoidable, irrespective of the care provided. The aim of this study was to explore Greek nurses' perceptions about the barriers involved and to identify the factors that influence care planning in PU treatment. METHOD: A grounded theory approach was used and semi-structured interviews were conducted with nurses who provided pressure care to clients in a rehabilitation centre in Greece. Data were analysed using the constant comparative method. RESULTS: We interviewed seven nurses. Findings revealed one main category entitled 'anarchy' in delivery of care consisted of the following three subcategories: interdisciplinary conflicts; total trust in traditional knowledge; and devaluation of other's work/role and a core category 'Against the odds': the perceived value of prevention and treatment can overcome the barriers in treating PUs. CONCLUSION: This study gives an overview of the views and beliefs of nurses about the problems and barriers involved in PU prevention and treatment. The study reveals that although some barriers to good practice may exist, nurses can hold a positive attitude toward PU prevention and treatment, and their perceived value of prevention and treatment may help nurses to overcome the barriers in managing PUs.

High prevalence of BRCA1 founder mutations in Greek breast/ovarian families.

We have screened 473 breast/ovarian cancer patients with family history, aiming to define the prevalence and enrich the spectrum of BRCA1/2 pathogenic mutations occurring in the Greek population. An overall mutation prevalence of 32% was observed. Six BRCA1 recurrent/founder mutations dominate the observed spectrum (58.5% of all mutations found). These include three mutations in exon 20 and three large genomic deletions. Of the 44 different deleterious mutations found in both genes, 16 are novel and reported here for the first time. Correlation with available histopathology data showed that 80% of BRCA1 carriers presented a triple-negative breast cancer phenotype while 82% of BRCA2 carriers had oestrogen receptor positive tumours. This study provides a comprehensive view of the frequency, type and distribution of BRCA1/2 mutations in the Greek population as well as an insight of the screening strategy of choice for patients of Greek origin. We conclude that the Greek population has a diverse mutation spectrum influenced by strong founder effects.

A multichannel feature-based approach for longitudinal lung CT registration in the presence of radiation induced lung damage.

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung computed tomography (CT) scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12 month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for three additional follow-up timepoints up to 48 months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection.

Characterization of a rabbit antihuman mechano growth factor (MGF) polyclonal antibody against the last 24 amino acids of the E domain.

The human insulin-like growth factor-1 (IGF-1) gene gives rise to multiple, heterogeneous mRNA transcripts by alternative splicing, thus producing different IGF-1 isoforms. The mechano growth factor (MGF) is an IGF-1 isoform that was found to be markedly up-regulated in exercised or damaged muscle. The specific E domain of the MGF splice variant may act as an independent growth factor. The aim of the present study was to characterize a rabbit antihuman MGF polyclonal antibody. New-Zealand rabbits were immunized by injections of a purified synthetic peptide corresponding to the last 24 amino acids of the human C-terminal of the MGF E domain. Western blotting and immunohistochemical techniques were used to characterize the specificity of the polyclonal anti-MGF antiserum. The anti-MGF antiserum was found to recognize the MGF E-peptide and not the common part of the IGF-1 isoforms, i.e. the mature IGF-1 peptide. Furthermore, it specifically bound to the MGF protein in human skeletal and in rat cardiac muscle, apparently due to the considerable homology between the human and rat MGF E-peptide sequences. Immunostaining analysis showed that this polyclonal anti-MGF antibody was able to detect MGF in human muscle and in rat cardiomyocytes and vessels' smooth muscle cells. We conclude that this rabbit polyclonal anti-human/rat MGF antibody could become a valuable tool in the study of IGF-1 isoforms in human and rat tissues.

A systematic review of single crowns on endodontically treated teeth.

OBJECTIVES: To test the hypothesis that the placement of a crown is associated with improved (long term) survival of root canal treated teeth, using a systematic review process of clinical studies. DATA SOURCES: Papers referring to single crowns on endodontically treated teeth were located by a MEDLINE search and hand searching. One thousand six hundred and nine references were found, and they were subjected to a systematic review procedure. STUDY SELECTION: A three-step inclusion-exclusion procedure was applied to identify papers that represented; good scientific practice (GSP), reported results of all patients, restorations on root canal treated teeth (RCT) for more than 2 years and had sufficient data to generate life table analyses. The outcomes were 'survival of RCT restored with crowns' and 'survival of RCT with direct restorations'. Ten studies survived. These data showed an overall mean GSP of 0.605 with a 10-year survival of 81% for crowned RCT and a 10-year survival of 63% for RCT with direct restorations (resin composites, amalgam, cements). CONCLUSION: RCTs restored with crowns show an acceptable long-term survival of 10 years, while direct restorations have a satisfactory survival only for a short period.

Serum Starvation Induces BACE1 Processing and Secretion.

BACKGROUND: ß-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aß peptides. Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. OBJECTIVE: To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1. METHOD: Detection of BACE1 secretion in BACE1 overexpressing cells or ADAM10/ADAM17 knockout fibroblasts cultured under serum deprivation conditions, using western blot analysis. RESULTS: We found that serum deprivation of U251 neuroblastoma or HEK293T cells overexpressing BACE1 stimulated secretion of BACE1. Using ADAM10/ADAM17 knockout fibroblasts and inhibitors of both ADAM10 and ADAM17, we obtained data indicating that these proteases are involved in serum-starvation induced shedding of BACE1. This is unexpected since BACE1 is localized mainly in lipid rafts while ADAM10 is localized mainly in nonlipid raft domains. We hypothesized that serum deprivation results in alterations in the lipid composition of the membrane which can alter the localization of ADAM10 and BACE1. In support, we obtained results indicating that extraction of membrane cholesterol following incubation with methyl ß cyclodextrin potentiated the effect of serum deprivation. Secreted BACE1 was also found to be enzymatically active towards immunoprecipiated full length APP. CONCLUSION: Serum starvation induces ADAM10-mediated BACE1 secretion.

Evaluation of modal damping factor as a diagnostic tool for osteoporosis and its relation with serum osteocalcin and collagen I N-telopeptide for monitoring the efficacy of alendronate in ovariectomized rats.

Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone microarchitecture. It results from the shift of the osteoblast-osteoclast activity equilibrium in favor of the later. Although, a number of biochemical markers, such as collagen I N-telopeptide (NTx) and osteocalcin (OC), have been used for monitoring bone remodeling, a new, monitoring, non-invasive method, which is based on the measurement of the dynamic characteristic of bone and is known as modal damping factor (MDF), has not been evaluated as a diagnostic tool for osteoporosis. Bisphosphonates, such as alendronate, have an established role in the treatment of osteoporosis. The aim of the present study was, therefore, to evaluate the effects of alendronate on the levels of MDF, serum NTx and OC on osteoporosis induced by ovariectomy in rats. Furthermore, the effects of alendronate on osteoporosis have been histologically evaluated. Fifteen adult female Wistar rats were bilaterally ovariectomized and osteoporosis was histologically confirmed and by the use of peripheral quantitative computerized tomography (pQCT). MDF was applied to assess the bone structural integrity. The serum levels of NTx (37.4+/-0.5 nM bone collagen equivalents, BCE) and OC (111.0+/-8.2 ng/mL) were found to significantly increase following ovariectomy (72.0+/-2.9 nM BCE and 213.5+/-12.1 ng/mL, respectively, p<0.001). As assessed by histology and the levels of NTx and OC in sera, animals treated with alendronate presented a statistically significant deceleration in the progression of the disease in comparison to the no-therapy control group (alendronate group NTx levels: 146.3+/-8.9 nM BCE versus no-therapy control group NTx levels: 265.3+/-14.0 nM BCE, p<0.001, alendronate group OC levels: 205.6+/-18.2 ng/mL versus no-therapy group OC levels: 353.9+/-26.1 ng/mL, p<0.001). Data obtained from the vibration analysis performed illustrated that the change in damping was equal or greater to the change in total and trabecular density, respectively. Damping increased with decreasing bone density, as expected, given that damping accounts for the structural integrity of bone (MDF value before ovariectomy: 0.058+/-0.003 versus MDF value after ovariectomy: 0.098+/-0.003, p<0.001). The higher damping values correspond to more deteriorated structures. In particular, both total and trabecular density were significantly decreased following ovariectomy (total density before ovariectomy: 702.4+/-19.0 versus total density after ovariectomy: 542.2+/-12.8, p<0.001, trabecular density before ovariectomy: 445.3+/-13.0 versus trabecular density after ovariectomy: 396.7+/-8.4, p<0.05). MDF value of the alendronate group (0.07+/-0.002) was significantly lower (p<0.001) as compared to MDF value after ovariectomy (0.098+/-0.003) and that of the no-therapy group (0.1+/-0.004, p<0.001). The administration of alendronate seemed to have no effect on either total or trabecular density, since both parameters continued to decrease (alendronate group total density: 549.4+/-12.3, alendronate group trabecular density: 368.4+/-14.7). However, when this was compared to the no-therapy group, a statistically significant difference of total density at the 0.05 level was observed (no-therapy total density: 464.8+/-9.1). The results of this study suggest that combined measurements of MDF, NTx and OC may be a potential diagnostic tool for osteoporosis and monitoring bone integrity during treatment with bisphosphonates. Furthermore, administration of alendronate showed to offer a critical deceleration in the progression of osteoporosis.

Genetic predisposition and IDDM in Greece.

Serological typing of HLA-DR antigens was performed on 116 patients with IDDM and 380 healthy controls. As expected a high incidence of HLA-DR3 and DR4 antigens was observed in patients with IDDM. However, the HLA-DR2 antigen, which rarely occurs in IDDM and is considered to confer protection against IDDM, was found in equal distribution (35%) in both patients and controls. HLA-DQ genotype analysis in 10 children with IDDM and 13 controls, all with the HLA-DR2 haplotype, showed that the great majority of affected children and normal controls carry the DR2 (16) or AZH-DQA1 *0102, DQB *0502 subtype. The high incidence of this subtype in normal individuals possibly explains why the DR2 antigen does not offer protection against IDDM in Greeks.

[@HOME is a new Eu-Project in Tele Home care]. / @Home ein neues Eu-Projekt zum Tele Home Care.

@Home is a robust platform for real-time remote monitoring of patients at their home by doctors at the hospital. Health monitoring sensors, which have the capability to measure quick and easy vital parameters such as blood pressure, pulse rate, temperature, oxygen saturation (SpO2), as well as ECG 12 leads are used. Additionally, an advantage of the platform is that all the sensors are wearable and the patient is able to walk around indoors or outdoors. Moreover, the sensors are able to convey the recorded data over Bluetooth, a short-range wireless communication, to any Bluetooth enabled device such as Desktop computer or a Pocket PC.

Vibrational bone characteristics versus bone density for the assessment of osteoporosis in ovariectomized rats.

Our previous research findings suggested this integrated study in order to monitor changes of bone properties and assess bone integrity using vibrational characteristics in osteoporosis. The method is based on measurement of the bone dynamic characteristic modal damping factor (MDF). The experimental animal model is ovariectomized rat followed by alendronate treatment. According to the experimental design, adult female Wistar rats are ovariectomized and 60 days later, with confirmed osteoporosis, the population is divided into two groups. One is administered alendronate and the second is given no treatment. Furthermore, established techniques such as pQCT and histomorphometry are applied at all time points, in order to compare and correlate to MDF. The results indicate induction of osteoporosis due to ovariectomy and render MDF capable of monitoring changes in bone material properties and architecture, with high sensitivity and repeatability.

FOXM1 is a transcriptional target of ERalpha and has a critical role in breast cancer endocrine sensitivity and resistance.

In this study, we investigated the regulation of FOXM1 expression by estrogen receptor alpha (ERalpha) and its role in hormonal therapy and endocrine resistance. FOXM1 protein and mRNA expression was regulated by ER-ligands, including estrogen, tamoxifen (OHT) and fulvestrant (ICI182780; ICI) in breast carcinoma cell lines. Depletion of ERalpha by RNA interference (RNAi) in MCF-7 cells downregulated FOXM1 expression. Reporter gene assays showed that ERalpha activates FOXM1 transcription through an estrogen-response element (ERE) located within the proximal promoter region. The direct binding of ERalpha to the FOXM1 promoter was confirmed in vitro by mobility shift and DNA pull-down assays and in vivo by chromatin immunoprecipitation (ChIP) analysis. Our data also revealed that upon OHT treatment ERalpha recruits histone deacetylases to the ERE site of the FOXM1 promoter, which is associated with a decrease in histone acetylation and transcription activity. Importantly, silencing of FOXM1 by RNAi abolished estrogen-induced MCF-7 cell proliferation and overcame acquired tamoxifen resistance. Conversely, ectopic expression of FOXM1 abrogated the cell cycle arrest mediated by the anti-estrogen OHT. OHT repressed FOXM1 expression in endocrine sensitive but not resistant breast carcinoma cell lines. Furthermore, qRT-PCR analysis of breast cancer patient samples revealed that there was a strong and significant positive correlation between ERalpha and FOXM1 mRNA expression. Collectively, these results show FOXM1 to be a key mediator of the mitogenic functions of ERalpha and estrogen in breast cancer cells, and also suggest that the deregulation of FOXM1 may contribute to anti-estrogen insensitivity.