Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

Sticker's sarcoma (also known as transmissible venereal tumor) is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT), treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations

Investigating the influence of product perception and geometric features

Research in emotional design and Kansei Engineering has shown that aesthetics play a significant role in the appeal of a product. This paper contributes to establishing a methodology to identify the relationships between perceptions, aesthetic features, desire to own and background of consumers. Surveys were conducted with 71 participants to gather their perceptions of 11 vase concepts. Advanced statistical analyses, including mixed models, were applied to allow generalisation of the results beyond the data sample. Significant relations between the desire to own a product and how the product is perceived were found (the desire to own was found to be related to beautiful, expensive, elegant, exciting, feminine, common and dynamic vases), as well as between the perceptions and the parameters describing the form of the vases (a vase was perceived as beautiful if it had many curved lines and was simple and tall). An automated mixed model analysis was conducted and revealed that general rules can be found between aesthetic features, perceptions and ownership, which can apply across gender and culture. The findings include design rules that link aesthetic features with perceptions. These contribute to research as guidelines for design synthesis and can either be implemented via shape grammars or parametric modelling approaches. These rules are also interesting for 3D printing applications, especially important when the consumer is the designer. Some of these design rules are linked to the desire to own a product, they have implications for industry, and they offer guidelines to creating attractive products that people want to own

Malaria training for community health workers in the setting of elimination: a qualitative study from China

Background: Continuous training of health workers is a key intervention to maintain their good performance and keep their vigilance during malaria elimination programmes. However, countries progressing toward malaria elimination have a largely decreased malaria disease burden, less frequent exposure of health workers to malaria patients, and new challenges in the epidemiology of the remaining malaria cases. Moreover, competing health priorities and usually a decline in resources and in political commitment also pose challenges to the elimination programme. As a consequence, the acceptability, sustainability, and impact of malaria training and education programmes face challenges. However, little is known of the perceptions and expectations of malaria training and education programmes of health workers being engaged in countries with malaria elimination programmes. Methods: This qualitative study provides information on perceptions and expectations of health workers of malaria training programmes from China, which aims to malaria elimination by the year 2020. This study was embedded into a larger study on the challenges and lessons learned during the malaria surveillance strategy in China, involving 42 interviews with malaria experts, health staff, laboratory practitioners, and village doctors at the provincial, city, county, township, and village levels from Gansu province (northwestern China) and Jiangsu province (southeastern China). Results: In the context of an increasing number of imported malaria cases in China, the majority of respondents emphasized the necessity and importance of such programmes and complained about a decreasing frequency of training courses. Moreover, they called for innovative strategies to improve the implementation and sustainability of the malaria training programmes until the elimination goal has been achieved. Perceptions and expectations of health workers from different health centres were quite different. Health workers from higher-level facilities were more concerned about technical training aspects, while health workers from periphery of the health system expected to receive more training on field work coordination and on specific public health actions with regard to case detection and focus investigation. Conclusions: There is need to guarantee an ongoing good training of health workers in China on malaria aspects until the year 2020 and probably beyond

Predicted Disappearance of Cephalantheropsis obcordata in Luofu Mountain Due to Changes in Rainfall Patterns

<div><h3>Background</h3><p>In the past century, the global average temperature has increased by approximately 0.74°C and extreme weather events have become prevalent. Recent studies have shown that species have shifted from high-elevation areas to low ones because the rise in temperature has increased rainfall. These outcomes challenge the existing hypothesis about the responses of species to climate change.</p> <h3>Methodology/Principal Findings</h3><p>With the use of data on the biological characteristics and reproductive behavior of <em>Cephalantheropsis obcordata</em> in Luofu Mountain, Guangdong, China, trends in the population size of the species were predicted based on several factors. The response of <em>C. obcordata</em> to climate change was verified by integrating it with analytical findings on meteorological data and an artificially simulated environment of water change. The results showed that <em>C. obcordata</em> can grow only in waterlogged streams. The species can produce fruit with many seeds by insect pollination; however, very few seeds can burgeon to become seedlings, with most of those seedlings not maturing into the sexually reproductive phase, and grass plants will die after reproduction. The current population's age pyramid is kettle-shaped; it has a Deevey type I survival curve; and its net reproductive rate, intrinsic rate of increase, as well as finite rate of increase are all very low. The population used in the artificial simulation perished due to seasonal drought.</p> <h3>Conclusions</h3><p>The change in rainfall patterns caused by climate warming has altered the water environment of <em>C. obcordata</em> in Luofu Mountain, thereby restricting seed burgeoning as well as seedling growth and shortening the life span of the plant. The growth rate of the <em>C. obcordata</em> population is in descending order, and models of population trend predict that the population in Luofu Mountain will disappear in 23 years.</p> </div

Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis

BACKGROUND: Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution. METHODS: A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues. RESULTS: We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer. CONCLUSION: The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution

Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer

Introduction: Endothelin (EDN) signalling plays a crucial role in cell differentiation, proliferation and migration processes. There is compelling evidence that altered EDN signalling is involved in carcinogenesis by modulating cell survival and promoting invasiveness. To date, most reports have focused on the oncogenic potential of EDN1 and EDN2, both of which are overexpressed in various tumour entities. Here, we aimed at a first comprehensive analysis on EDN3 expression and its implication in human breast cancer. Methods: EDN3 mRNA expression was assessed by Northern blotting in normal human tissues (n = 9) as well as in matched pairs of normal and tumourous tissues from breast specimens (n = 50). EDN3 mRNA expression in breast cancer was further validated by real-time polymerase chain reaction (PCR) (n = 77). A tissue microarray was used to study EDN3 protein expression in breast carcinoma (n = 150) and normal breast epithelium (n = 44). EDN3 promoter methylation was analysed by methylation-specific PCR in breast cell lines (n = 6) before and after demethylating treatment, normal breast tissues (n = 17) and primary breast carcinomas (n = 128). EDN3 expression and methylation data were statistically correlated with clinical patient characteristics and patient outcome. Results: Loss of EDN3 mRNA expression in breast cancer, as initially detected by array-based expression profiling, could be confirmed by Northern blot analysis (> 2-fold loss in 96%) and real-time PCR (> 2-fold loss in 78%). Attenuated EDN3 expression in breast carcinoma was also evident at the protein level (45%) in association with adverse patient outcome in univariate (P = 0.022) and multivariate (hazard ratio 2.0; P = 0.025) analyses. Hypermethylation of the EDN3 promoter could be identified as the predominant mechanism leading to gene silencing. Reversion of the epigenetic lock by 5-aza-2'-deoxycytidine and trichostatin A resulted in EDN3 mRNA reexpression in vitro. Furthermore, EDN3 promoter hypermethylation was detected in 70% of primary breast carcinomas with significant association to loss of EDN3 mRNA expression (P = 0.005), whilst normal matched breast tissues revealed no EDN3 promoter methylation. Conclusions EDN3 is a frequent target of epigenetic inactivation in human breast cancer, potentially contributing to imbalanced EDN signalling commonly found in this disease. The clinical implication supports the view that EDN3, in contrast to EDN1 and EDN2, may act as natural tumour suppressor in the human mammary gland

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

Background: Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival.Results: By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems.Conclusions: Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.Financial support was provided by grants BFU2009-12895-C02-01/BMC (Ministerio de Ciencia e Innovación, Spain), the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 212894 and Prometeo/2009/092 (Conselleria d’Educació, Generalitat Valenciana, Spain) to A. Moya. Work in the FdlC laboratory was supported by grants BFU2008-00995/BMC (Spanish Ministry of Education), RD06/0008/1012 (RETICS research network, Instituto de Salud Carlos III, Spanish Ministry of Health) and LSHM-CT- 2005_019023 (European VI Framework Program). Dr. González-Domenech was supported by grant from the University of Granada. LD, thanks to financial support from Facultad de Ciencias, Universidad Nacional Autónoma de México