A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study)

Contains fulltext : 87553.pdf (publisher's version ) (Open Access)BACKGROUND: The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? METHOD/DESIGN: The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3 x 40 = 120 patients is calculated. DISCUSSION: The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. TRIAL REGISTRATION: ISRCTN44649165

Mental health first aid training for nursing students: a protocol for a pragmatic randomised controlled trial in a large university

BackgroundThe impact of mental health problems and disorders in Australia is significant. Mental health problems often start early and disproportionately affect young people. Poor adolescent mental health can predict educational achievement at school and educational and occupational attainment in adulthood. Many young people attend higher education and have been found to experience a range of mental health issues. The university setting therefore presents a unique opportunity to trial interventions to reduce the burden of mental health problems. Mental Health First Aid (MHFA) aims to train participants to recognise symptoms of mental health problems and assist an individual who may be experiencing a mental health crisis. Training nursing students in MHFA may increase mental health literacy and decrease stigma in the student population. This paper presents a protocol for a trial to examine the efficacy of the MHFA training for students studying nursing at a large university in Perth, Western Australia. Methods/DesignThis randomised controlled trial will follow the CONSORT guidelines. Participants will be randomly allocated to the intervention group (receiving a MHFA training course comprising two face to face 6.5 hour sessions run over two days during the intervention period) or a waitlisted control group (not receiving MHFA training during the study). The source population will be undergraduate nursing students at a large university located in Perth, Western Australia. Efficacy of the MHFA training will be assessed by following the intention-to-treat principle and repeated measures analysis. DiscussionGiven the known burden of mental health disorders among student populations, it is important universities consider effective strategies to address mental health issues. Providing MHFA training to students offers the advantage of increasing mental health literacy, among the student population. Further, students trained in MHFA are likely to utilise these skills in the broader community, when they graduate to the workforce. It is anticipated that this trial will demonstrate the scalability of MHFA in the university environment for pre-service nurses and that implementation of MHFA courses, with comprehensive evaluation, could yield positive improvements in the mental health literacy amongst this target group as well as other tertiary student groups. Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN1261400086165

Regulatory elements and transcriptional control of chicken vasa homologue (CVH) promoter in chicken primordial germ cells

BACKGROUND: Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis- and trans-regulatory elements. Studies on gene structures of chicken vasa homologue (CVH), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells. However, very limited studies are available on regulatory elements that control germ cell-specific expression in chicken. Therefore, we investigated the intricate regulatory mechanism(s) that governs transcriptional control of CVH. RESULTS: We constructed green fluorescence protein (GFP) or luciferase reporter vectors containing the various 5′ flanking regions of CVH gene. From the 5′ deletion and fragmented assays in chicken PGCs, we have identified a CVH promoter that locates at −316 to +275 base pair fragment with the highest luciferase activity. Additionally, we confirmed for the first time that the 5′ untranslated region (UTR) containing intron 1 is required for promoter activity of the CVH gene in chicken PGCs. Furthermore, using a transcription factor binding prediction, transcriptome analysis and siRNA-mediated knockdown, we have identified that a set of transcription factors play a role in the PGC-specific CVH gene expression. CONCLUSIONS: These results demonstrate that cis-elements and transcription factors localizing in the 5′ flanking region including the 5′ UTR and an intron are important for transcriptional regulation of the CVH gene in chicken PGCs. Finally, this information will contribute to research studies in areas of reproductive biology, constructing of germ cell-specific synthetic promoter for tracing primordial germ cells as well as understanding the transcriptional regulation for maintaining germness in PGCs

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology

Interactions between Schistosoma haematobium group species and their Bulinus spp. intermediate hosts along the Niger River Valley

Background Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology. Methods Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20–52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region). Results A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2–10 MLG’s) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed. Conclusions This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development

Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation