Unmet psychosocial needs in haematological cancer: A systematic review

The final publication is available at Springer via http://dx.doi.org/10.1007/s00520-014-2123-5A systematic review of key online databases and psycho-oncology journals was conducted to identify papers that formally assessed unmet psychosocial needs in adults with a diagnosis of haematological cancer

Mitochondrial DNA and trade data support multiple origins of Helicoverpa armigera (Lepidoptera, Noctuidae) in Brazil

The Old World bollworm Helicoverpa armigera is now established in Brazil but efforts to identify incursion origin(s) and pathway(s) have met with limited success due to the patchiness of available data. Using international agricultural/horticultural commodity trade data and mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) gene markers, we inferred the origins and incursion pathways into Brazil. We detected 20 mtDNA haplotypes from six Brazilian states, eight of which were new to our 97 global COI-Cyt b haplotype database. Direct sequence matches indicated five Brazilian haplotypes had Asian, African, and European origins. We identified 45 parsimoniously informative sites and multiple substitutions per site within the concatenated (945 bp) nucleotide dataset, implying that probabilistic phylogenetic analysis methods are needed. High diversity and signatures of uniquely shared haplotypes with diverse localities combined with the trade data suggested multiple incursions and introduction origins in Brazil. Increasing agricultural/horticultural trade activities between the Old and New Worlds represents a significant biosecurity risk factor. Identifying pest origins will enable resistance profiling that reflects countries of origin to be included when developing a resistance management strategy, while identifying incursion pathways will improve biosecurity protocols and risk analysis at biosecurity hotspots including national ports

Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30 hours. The above system and resource provide tools to study morphogen function in development

STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice

Deregulated activation of STAT3 is frequently associated with many human hematological and epithelial malignancies, including gastric cancer. While exaggerated STAT3 signaling facilitates an antiapoptotic, proangiogenic, and proproliferative environment for neoplastic cells, the molecular mechanisms leading to STAT3 hyperactivation remain poorly understood. Using the gp(Y757F/Y757F) mouse model of gastric cancer, which carries a mutated gp130 cytokine receptor signaling subunit that cannot bind the negative regulator of cytokine signaling SOCS3 and is characterized by hyperactivation of the signaling molecules STAT1 and STAT3, we have provided genetic evidence that IL- 11 promotes chronic gastric inflammation and associated tumorigenesis. Expression of IL-11 was increased in gastric tumors in gp(130Y757F/Y757F) mice, when compared with unaffected gastric tissue in wild-type mice, while gp(130Y757F/Y757F) mice lacking the IL-11 ligand-binding receptor subunit (IL-11R alpha) showed normal gastric STAT3 activation and IL-11 expression and failed to develop gastric tumors. Furthermore, reducing STAT3 activity in gp(130Y757F/Y757F) mice, either genetically or by therapeutic administration of STAT3 antisense oligonucleotides, normalized gastric IL- 11 expression and alleviated gastric tumor burden. Surprisingly, the genetic reduction of STAT1 expression also reduced gastric tumorigenesis in gp(130Y757F/Y757F) mice and coincided with reduced gastric inflammation and IL-11 expression. Collectively, our data have identified IL- 11 as a crucial cytokine promoting chronic gastric inflammation and associated tumorigenesis mediated by excessive activation of STAT3 and STAT1

Creating testable questions in practical conservation: a process and 100 questions

It is now clear that the routine embedding of experiments into conservation practice is essential for creating reasonably comprehensive evidence of the effectiveness of actions. However, an important barrier is the stage of identifying testable questions that are both useful but also realistic to carry out without a major research project. We identified approaches for generating such suitable questions. A team of 24 participants crowdsourced suggestions, resulting in a list of a hundred possible tests of actions.The David and Claudia Harding Foundatio

Assessing the impact of diagnosis and the related supportive care needs in patients with cutaneous melanoma

PURPOSE: Despite the large number of people affected by melanoma, little is known about the specific needs of melanoma patients. Understanding the effects of melanoma diagnosis and the specific supportive care needs of this group of patients is a necessary step towards provision of effective psychosocial care. METHODS: Semi-structured interviews were carried out with 15 patients with malignant melanoma of the skin. The sample size, which was purposive, included 8 females and 7 males from 27 to 78 years old. Data were analysed using the NVIVO 8 software and principles of thematic analysis. RESULTS: Four major areas were identified: (a) Emotional effects due to body image, fear of the sun and uncertainty for the future; (b) Effects on Relationships, with some patients in need of more support than others from family and work colleagues; (c) Functional effects due to on-going symptoms such as pain and lymphedema; and (d) Health System and Information Needs, around the clarity, quality and timing of the information received from the health care professionals. CONCLUSIONS: The findings suggest that we often fail to pick up melanoma patients' health and psychosocial needs and fail to refer them appropriately, rather than the services not being available. Interventions should focus on patient and carer education about melanoma and sun protection, psychosocial support and effective information giving. Patient-reported outcome measures should routinely be collected to identify issues of specific concerns to the patients and directing them to the right services based on their individual needs