An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins.

Enteropathogenic Escherichia coli (EPEC) is an attaching and effacing (A/E) human pathogen that causes diarrhea during acute infection, and it can also sustain asymptomatic colonization. A/E E. coli depletes host cell DNA mismatch repair (MMR) proteins in colonic cell lines and has been detected in colorectal cancer (CRC) patients. However, until now, a direct link between infection and host mutagenesis has not been fully demonstrated. Here we show that the EPEC-secreted effector protein EspF is critical for complete EPEC-induced depletion of MMR proteins. The mechanism of EspF activity on MMR protein was posttranscriptional and dependent on EspF mitochondrial targeting. EPEC infection also induced EspF-independent elevation of host reactive oxygen species levels. Moreover, EPEC infection significantly increased spontaneous mutation frequency in host cells, and this effect was dependent on mitochondrially targeted EspF. Taken together, these results support the hypothesis that A/E E. coli can promote colorectal carcinogenesis in humans

Physiotherapists’ perception of a community-based primary healthcare clinical education approach to undergraduate learning

Background. South African health systems are challenged by numerous stressors, such as a lack of resources, staff shortages and overburdened public sector demands. This necessitates appropriately equipped and trained healthcare professionals to meet the demands of this system. Community-based primary healthcare (PHC) clinical education is an approach towards preparing health science students to meet these demands. Clinical education is the cornerstone of undergraduate training. Physiotherapists are among the healthcare professionals who require undergraduate training that drives competence for independent practice.Objective. To explore the perceptions and experiences of physiotherapists as clinical supervisors within a physiotherapy undergraduate programme that adopted a community-based PHC approach to clinical training.Methods. An explorative qualitative approach was used, with semi-structured interviews with 10 purposively selected physiotherapists supervising students on the newly introduced platform. Data were transcribed and analysed using content analysis.Results. Seven themes emerged from the data, which relate to curriculum redress, organisational factors, stakeholder dynamics, barriers and enablers to decentralised clinical training, perceived preparedness for practice and recommendations.Conclusions. As the need for an increasing number of health professionals is realised, more innovative methods for clinical education of undergraduate health science students are required. Community-based PHC training for physiotherapy students is one such approach and was generally perceived as a valuable framework to incorporate competencies required for practice as future independent practitioners. Furthermore, improved communication between students, clinicians and academic staff was seen as a recommendation to influence clinical education

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study.

BACKGROUND: Recruitment and retention in clinical trials remains an important challenge, particularly in the context of advanced disease. It is important to understand what affects retention to improve trial quality, minimise attrition and reduce missing data. We conducted a qualitative study embedded within a randomised feasibility trial and explored what influenced people to take part and remain in the trial. METHODS: We conducted a qualitative study embedded within a double-blind randomised trial (BETTER-B[Feasibility]: BETter TreatmEnts for Refractory Breathlessness) designed using a person-centred approach. Participants with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or chronic heart failure (CHF), with a modified Medical Research Council dyspnoea scale grade of 3/4 were recruited from three UK sites. A convenience subsample completed qualitative interviews after the trial. Interviews were analysed using thematic analysis. Results were considered in relation to the core elements of person-centred care and our model of the person-centred trial. RESULTS: In the feasibility trial 409 people were screened for eligibility, and 64 were randomised. No participant was lost to follow-up. Twenty-two participants took part in a qualitative interview. Eleven had a diagnosis of COPD, 8 ILD, 2 CHF and 1 lung cancer. The participants' median age was 71 years (range 56-84). Sixteen were male. Twenty had completed the trial, and two withdrew due to adverse effects. The relationship between patient and professional, potential for benefit, trial processes and the intervention all influenced the decision to participate in the trial. The relationship with the research team and continuity, perceived benefit, and aspects relating to trial processes and the intervention influenced the decision to remain in the trial. CONCLUSIONS: In this feasibility trial recruitment targets were met, attrition levels were low, and aspects of the person-centred approach were viewed positively by trial participants. Prioritisation of the relationship between the patient and professional; person-centred processes, including home visits, assistance with questionnaires, and involvement of the carer; and enabling people to participate by having processes in line with individual capabilities appear to support recruitment and retention in clinical trials in advanced disease. We recommend the integration of a person-centred approach in all clinical trials. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN32236160. Registered on 13 June 2016

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Investigating Hastily-Formed Collaborative Networks

This research explores both the human and technical aspects of the network centric environment in the context of a major disaster or incident of national significance. The National Incident Management System (NIMS) is viewed by the authors as a social network, and an organizational topology is developed to improve its effectiveness. A rapid Network Deployment Kit (RNDK) using commercial off the shelf (COTS) wireless networking technology is also proposed that facilitates immediate NIMS implementation. The integration of logical and technical analyses forms a comprehensive systems engineering proposal to facilitate collaboration in a net-centric environment. It is envisioned that the methodology used herein to derive and evaluate comprehensive networks proves extendable to other contexts thereby contributing to the netcentric body of knowledge