A qualitative assessment of implementing a cross-cultural survey on cancer wards in Denmark - a description of barriers

<p>Abstract</p> <p>Background</p> <p>Research into migration and health is often confronted with methodological challenges related to the identification of migrants in various settings. Furthermore, it is often difficult to reach an acceptable level of participation among migrant groups in quantitative research. The aim of this study is to conduct a qualitative assessment of the barriers encountered during the implementation of a cross-cultural survey on cancer wards in Copenhagen, Denmark.</p> <p>Methods</p> <p>Participant observation at the involved wards was combined with qualitative interviews with selected nurses and informal talks with a wider group of nurses at the wards involved in the survey.</p> <p>Results</p> <p>One possible way to increase the participation of migrant patients in research is through the involvement of the hospital staff in contact with patients. Involvement of nurses on cancer wards in the delivery of questionnaires to patients was challenging, despite a general willingness to participate in psychosocial research. The main difficulties were found to be both external (policy changes, general strike among nurses) and internal on the wards (heavy workload, lack of time, focus on medical aspects of cancer rather than psychosocial aspects). These factors interacted and resulted in a lower priority being given to psychosocial research. Further, nurses expressed a feeling that researchers in general did not recognize their contribution in research, making it more difficult to engage fully in studies.</p> <p>Conclusions</p> <p>Involving hospital staff in research is feasible but not straightforward. Awareness of the influence of possible external and internal factors and efforts to deal with these factors are fundamental to the successful implementation of psychosocial cancer research in a hospital setting.</p

Feeding Behaviour, Swimming Activity and Boldness Explain Variation in Feed Intake and Growth of Sole (Solea solea) Reared in Captivity

The major economic constraint for culturing sole (Solea solea) is its slow and variable growth. The objective was to study the relationship between feed intake/efficiency, growth, and (non-) feeding behaviour of sole. Sixteen juveniles with an average (SD) growth of 2.7 (1.9) g/kg0.8/d were selected on their growth during a 4-week period in which they were housed communally with 84 other fish. Selected fish were housed individually during a second 4-week period to measure individual feed intake, growth, and behaviour. Fish were hand-fed three times a day during the dark phase of the day until apparent satiation. During six different days, behaviour was recorded twice daily during 3 minutes by direct observations. Total swimming activity, frequency of burying and of escapes were recorded. At the beginning and end of the growth period, two sequential behavioural tests were performed: “Novel Environment” and “Light Avoidance”. Fish housed individually still exhibited pronounced variation in feed intake (CV = 23%), growth (CV = 25%) and behavior (CV = 100%). Differences in feed intake account for 79% of the observed individual differences in growth of sole. Fish with higher variation in feed intake between days and between meals within days had significantly a lower total feed intake (r = −0.65 and r = −0.77) and growth. Active fish showed significantly higher feed intake (r = 0.66) and growth (r = 0.58). Boldness during both challenge tests was related to fast growth: (1) fish which reacted with a lower latency time to swim in a novel environment had significantly higher feed intake (r = −0.55) and growth (r = −0.66); (2) fish escaping during the light avoidance test tended to show higher feed intake (P<0.1) and had higher growth (P<0.05). In conclusion, feeding consistency, swimming activity in the tank, and boldness during behavioral tests are related to feed intake and growth of sole in captivity

ALCAM Regulates Motility, Invasiveness, and Adherens Junction Formation in Uveal Melanoma Cells

ALCAM, a member of the immunoglobulin superfamily, has been implicated in numerous developmental events and has been repeatedly identified as a marker for cancer metastasis. Previous studies addressing ALCAM’s role in cancer have, however, yielded conflicting results. Depending on the tumor cell type, ALCAM expression has been reported to be both positively and negatively correlated with cancer progression and metastasis in the literature. To better understand how ALCAM might regulate cancer cell behavior, we utilized a panel of defined uveal melanoma cell lines with high or low ALCAM levels, and directly tested the effects of manipulating these levels on cell motility, invasiveness, and adhesion using multiple assays. ALCAM expression was stably silenced by shRNA knockdown in a high-ALCAM cell line (MUM-2B); the resulting cells displayed reduced motility in gap-closure assays and a reduction in invasiveness as measured by a transwell migration assay. Immunostaining revealed that the silenced cells were defective in the formation of adherens junctions, at which ALCAM colocalizes with N-cadherin and ß-catenin in native cells. Additionally, we stably overexpressed ALCAM in a low-ALCAM cell line (MUM-2C); intriguingly, these cells did not exhibit any increase in motility or invasiveness, indicating that ALCAM is necessary but not sufficient to promote metastasis-associated cell behaviors. In these ALCAM-overexpressing cells, however, recruitment of ß-catenin and N-cadherin to adherens junctions was enhanced. These data confirm a previously suggested role for ALCAM in the regulation of adherens junctions, and also suggest a mechanism by which ALCAM might differentially enhance or decrease invasiveness, depending on the type of cadherin adhesion complexes present in tissues surrounding the primary tumor, and on the cadherin status of the tumor cells themselves

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe

Transcriptional Analysis Implicates Endoplasmic Reticulum Stress in Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy (BSE) is a fatal, transmissible, neurodegenerative disease of cattle. To date, the disease process is still poorly understood. In this study, brain tissue samples from animals naturally infected with BSE were analysed to identify differentially regulated genes using Affymetrix GeneChip Bovine Genome Arrays. A total of 230 genes were shown to be differentially regulated and many of these genes encode proteins involved in immune response, apoptosis, cell adhesion, stress response and transcription. Seventeen genes are associated with the endoplasmic reticulum (ER) and 10 of these 17 genes are involved in stress related responses including ER chaperones, Grp94 and Grp170. Western blotting analysis showed that another ER chaperone, Grp78, was up-regulated in BSE. Up-regulation of these three chaperones strongly suggests the presence of ER stress and the activation of the unfolded protein response (UPR) in BSE. The occurrence of ER stress was also supported by changes in gene expression for cytosolic proteins, such as the chaperone pair of Hsp70 and DnaJ. Many genes associated with the ubiquitin-proteasome pathway and the autophagy-lysosome system were differentially regulated, indicating that both pathways might be activated in response to ER stress. A model is presented to explain the mechanisms of prion neurotoxicity using these ER stress related responses. Clustering analysis showed that the differently regulated genes found from the naturally infected BSE cases could be used to predict the infectious status of the samples experimentally infected with BSE from the previous study and vice versa. Proof-of-principle gene expression biomarkers were found to represent BSE using 10 genes with 94% sensitivity and 87% specificity

Gene Expression Analysis Implicates a Death Receptor Pathway in Schizophrenia Pathology

An increase in apoptotic events may underlie neuropathology in schizophrenia. By data-mining approaches, we identified significant expression changes in death receptor signaling pathways in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia, particularly implicating the Tumor Necrosis Factor Superfamily member 6 (FAS) receptor and the Tumor Necrosis Factor [ligand] Superfamily member 13 (TNFSF13) in schizophrenia. We sought to confirm and replicate in an independent tissue collection the noted mRNA changes with quantitative real-time RT-PCR. To test for regional and diagnostic specificity, tissue from orbital frontal cortex (OFC) was examined and a bipolar disorder group included. In schizophrenia, we confirmed and replicated significantly increased expression of TNFSF13 mRNA in the DLPFC. Also, a significantly larger proportion of subjects in the schizophrenia group had elevated FAS receptor expression in the DLPFC relative to unaffected controls. These changes were not observed in the bipolar disorder group. In the OFC, there were no significant differences in TNFSF13 or FAS receptor mRNA expression. Decreases in BH3 interacting domain death agonist (BID) mRNA transcript levels were found in the schizophrenia and bipolar disorder groups affecting both the DLPFC and the OFC. We tested if TNFSF13 mRNA expression correlated with neuronal mRNAs in the DLPFC, and found significant negative correlations with interneuron markers, parvalbumin and somatostatin, and a positive correlation with PPP1R9B (spinophilin), but not DLG4 (PSD-95). The expression of TNFSF13 mRNA in DLPFC correlated negatively with tissue pH, but decreasing pH in cultured cells did not cause increased TNFSF13 mRNA nor did exogenous TNFSF13 decrease pH. We concluded that increased TNFSF13 expression may be one of several cell-death cytokine abnormalities that contribute to the observed brain pathology in schizophrenia, and while increased TNFSF13 may be associated with lower brain pH, the change is not necessarily causally related to brain pH

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Innovative solutions to enhance safe and green environments for ageing well using co-design through Patient and Public Involvement.

Background: There is a need to develop innovative solutions to enhance safe and green physical environments, which optimise health, wellbeing and community participation among older adults. In order to develop solutions that meet the needs of a diverse ageing population, an interdisciplinary approach is needed. Our aim was to identify the needs of older people in relation to ageing well in the environment by bringing together knowledge from different perspectives using Patient and Public Involvement. Methods: An international consortium (Retrofit living For ageing well through Understanding and Redesign of Built environments consortium: ReFURB) was established in April 2018, including ten core members, to (i) explore cutting-edge solutions to safe living for ageing populations and (ii) develop innovative approaches to everyday physical environments, which bring about health benefits. We used a co-design, interdisciplinary framework involving older adults, carers, physiotherapists, geriatricians, engineers, human movement experts, geographers and psychologists from the UK and Australia. This engaged people in a one day workshop that comprised a series of presentations from international speakers on urban design, social connectedness, hazards and injury prevention, and the physical environment. Small group discussions (facilitated by consortium members) followed presentations to consider the opportunities, challenges and barriers encountered with ageing, which included the use of creative engagement activities (LEGO® Serious Play, mind maps, poster gallery walk), to help participants share personal stories and reflect on the issues raised. Thematic coding was used to synthesise the outputs of the small group work. Results: Five themes were identified across the workshops, comprising: access and transport; involvement of the whole community; restoration rather than redesign; assistive and digital technology; and intergenerational approaches. These dimensions related to the physical, social and nature-based qualities of everyday environments, as they pertain to ageing well. Conclusions: Co-design was a valuable tool that helped understand the perceptions of participants and essential to develop effective interventions and solutions. Participants highlighted several issues affecting people as they age and key environmental considerations to promote wellbeing, activity, and participation. The consortium identified gaps in the existing evidence base and are now planning activities to further develop research ideas in collaboration with our co-design participants