The Effects of cis-9, trans-11 Conjugated Linoleic Acid on the Proliferation of A431 Epidermoid Carcinoma Cells

Conjugated linoleic acid (CLA) is a family of 28 positional and geometrical isomers of linoleic acid (LA), found predominantly in the meat of ruminant animals. The health benefits of CLA have been widely researched, with specific interest into its anti-obesity and anti-carcinogenic properties. Conclusions from in-vivo studies have suggested that, with further research, CLA supplementation may be used in conjunction with current treatments for breast cancer and rectal cancer. In-vitro research into the anticarcinogenic effects of CLA has revealed that different CLA isomers affect cancer cells through several different pathways. The anti-proliferative effects of cis-9, trans-11 CLA and trans-10, cis-12 CLA have been demonstrated in-vitro, specifically on colon cancer, breast cancer, and prostate cancer. Ultimately, it has been concluded that the antiproliferative effects of CLA isomers are dependent upon the type and malignancy of the cancer cells targeted. After reviewing the literature, it is clear that there is a gap in the research. To our knowledge, no study has ever tested the effects of CLA on the proliferation of epidermoid carcinoma cells, specifically the cis-9, trans-11 CLA isomer. This research could add to the growing body of evidence surrounding the effects of specific CLA isomers on different types of cancer in-vitro

Short Report: Initial Pilot of a Brief Career Development Program for Autistic Young Adults

Background Many autistic young adults may struggle to progress to further education or employment after high school, highlighting the need for tailored career development programs. If provided with the proper resources and support, the obstacles faced by autistic youth in pursuing post-secondary activities may decrease. Aims This pilot study aimed to examine the feasibility and preliminary efficacy of a brief career development program consisting of a strengths and challenges intervention paired with a 12-week workshop intervention. Methods and procedures We studied the participants\u27 changes in confidence and participation in pursuing post-secondary activities using a series of questionnaires in 20 participants, ages 16–23. The Myers-Briggs Type Indicator (MBTI) and Strong Interest Inventory (SII) helped the participants choose a post-secondary path. The 1–9 Vocational Index Scale measured post-secondary participation and hours working in a normed fashion. The Confidence Index Interval: Entering Workforce measured the participants’ perceived confidence related to career transition. Outcomes and results Our results suggested that a brief career development program paired with a strengths and challenges intervention significantly increased post-secondary involvement in autistic young adults (N = 20, p = 0.014). There were no significant changes in confidence. Conclusions and implications These findings provide proof of concept of a brief career development program using the MBTI and SII in young adults with ASD. What this paper adds Research in career development and transition for autistic young adults reveals that career interventions specific to the autistic population are lacking. Our pilot study explores a new type of intervention that incorporates the analysis of personal strengths and challenges with a 12-week transition workshop. Our project is the first to utilize the MBTI and SII as a tool to guide autistic youth in choosing a post-secondary path. The results of our study suggest that our program significantly improves post-secondary participation in autistic young adults. The findings provide proof of concept of using the MTBI and SII with a 12-week workshop for autistic young adults. At the end of our program, several participants began pursuing post-secondary education on track to obtain associate’s (N = 8) or bachelor’s (N = 3) degrees. Some began trade school (N = 3) and internships (N = 2), and others began employment or onboarding to employment (N = 4). Given the need for more evidence-based career interventions for autistic adults, our pilot study contributes significantly to autism research to better serve the autistic population

Evaluating interventions to improve ethical decision making in clinical practice : a review of the literature and reflections on the challenges posed

Since the 1980s, there has been an increasing acknowledgement of the importance of recognising the ethical dimension of clinical decision-making. Medical professional regulatory authorities in some countries now include ethical knowledge and practice in their required competencies for undergraduate and post graduate medical training. Educational interventions and clinical ethics support services have been developed to support and improve ethical decision making in clinical practice, but research evaluating the effectiveness of these interventions has been limited. We undertook a systematic review of the published literature on measures or models of evaluation used to assess the impact of interventions to improve ethical decision making in clinical care. We identified a range of measures to evaluate educational interventions, and one tool used to evaluate a clinical ethics support intervention. Most measures did not evaluate the key impact of interest, that is the quality of ethical decision making in real-world clinical practice. We describe the results of our review and reflect on the challenges of assessing ethical decision making in clinical practice that face both developers of educational and support interventions and the regulatory organisations that set and assess competency standards

Active travel to schools in Wales

Objectives Active travel to school (ATS), such as walking and cycling, not only reduces carbon emissions and air pollution but also contributes to a myriad of health benefits. Understanding the ‘potential’ for ATS across Wales is poorly understood yet vital to inform policy and practice aimed at increasing ATS. Methods Using geospatial techniques, network distances have been calculated for all residences to all schools in Wales. Distances for each residence were de-identified and imported into the Secure Anonymised Information Linkage (SAIL) databank using SAIL’s split file approach. Within SAIL, anonymised distances were linked to encrypted school locations and a cohort of approximately 440,000 children attending a state school in Wales as recorded in the Education Wales (EDUW) dataset. Travel distance to school was subsequently filtered for each child within our cohort. Results The incorporation of geospatial network derived origin-destination pairs (n=2,205,000,000) allows us to explore how households can engage in ATS, and how this varies by primary/secondary school, welsh-speaking, urban/rural, and socioeconomic status. Initially we will present findings based on distance alone, with future refinements to encompass other factors influencing ATS including: active travel routes, road safety, and topography. We will link our results to anonymised ATS survey responses in SAIL, to calculate specific ATS distance thresholds by age, deprivation, and urban/rural status, including social indicators such as household composition. Conclusion Currently there is limited local or national comparable information on the potential for ATS in Wales. This baseline information is urgently needed to inform ATS policy and planning, and to ensure appropriate ATS interventions are prioritised for schools and communities where need is greatest

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TRAF2 facilitates Vaccinia virus replication by promoting rapid virus entry.

Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is a pivotal intracellular mediator of signaling pathways downstream of TNFR1 and -2 with known pro- and antiviral effects. We investigated its role in the replication of the prototype poxvirus vaccinia virus (VACV). Loss of TRAF2 expression, either through small interfering RNA treatment of HeLa cells or through genetic knockout in murine embryonic fibroblasts (MEFs), led to significant reductions in VACV growth following low-multiplicity infection. In single-cycle infections, there was delayed production of both early and late VACV proteins as well as accelerated virus-induced alterations to cell morphology, indicating that TRAF2 influences early stages of virus replication. Consistent with an early role, uncoating assays showed normal virus attachment but delayed virus entry in the absence of TRAF2. Although alterations to c-Jun N-terminal kinase (JNK) signaling were apparent in VACV-infected TRAF2(−/−) MEFs, treatment of wild-type cells with a JNK inhibitor did not affect virus entry. Instead, treatment with an inhibitor of endosomal acidification greatly reduced virus entry into TRAF2(−/−) MEFs, suggesting that VACV is reliant on the endosomal route of entry in the absence of TRAF2. Thus, TRAF2 is a proviral factor for VACV that plays a role in promoting efficient viral entry, most likely via the plasma membrane. IMPORTANCE Tumor necrosis factor receptor-associated factors (TRAFs) are key facilitators of intracellular signaling with roles in innate and adaptive immunity and stress responses. We have discovered that TRAF2 is a proviral factor in vaccinia virus replication in both HeLa cells and mouse embryonic fibroblasts and that its influence is exercised through promotion of efficient virus entry

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A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference

Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics

Permissive and Restricted Virus Infection of Murine Embryonic Stem Cells

Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA 'off-target' effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host-pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host-virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host-virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence