Cellular interactions with polystyrene nanoplastics-The role of particle size and protein corona.

Plastic waste is ubiquitously spread across the world and its smaller analogs-microplastics and nanoplastics-raise particular health concerns. While biological impacts of microplastics and nanoplastics have been actively studied, the chemical and biological bases for the adverse effects are sought after. This work explores contributory factors by combining results from in vitro and model mammalian membrane experimentation to assess the outcome of cell/nanoplastic interactions in molecular detail, inspecting the individual contribution of nanoplastics and different types of protein coronae. The in vitro study showed mild cytotoxicity and cellular uptake of polystyrene (PS) nanoplastics, with no clear trend based on nanoplastic size (20 and 200 nm) or surface charge. In contrast, a nanoplastic size-dependency on bilayer disruption was observed in the model system. This suggests that membrane disruption resulting from direct interaction with PS nanoplastics has little correlation with cytotoxicity. Furthermore, the level of bilayer disruption was found to be limited to the hydrophilic headgroup, indicating that transmembrane diffusion was an unlikely pathway for cellular uptake-endocytosis is the viable mechanism. In rare cases, small PS nanoplastics (20 nm) were found in the vicinity of chromosomes without a nuclear membrane surrounding them; however, this was not observed for larger PS nanoplastics (200 nm). We hypothesize that the nanoplastics can interact with chromosomes prior to nuclear membrane formation. Overall, precoating PS particles with protein coronae reduced the cytotoxicity, irrespective of the corona type. When comparing the two types, the extent of reduction was more apparent with soft than hard corona

An <i>In Vivo</i> Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer.

Chemotherapy remains the mainstay of treatment for advanced breast cancer; however, resistance is an inevitable event for the majority of patients with metastatic disease. Moreover, there is little information available to guide stratification of first-line chemotherapy, crucial given the common development of multidrug resistance. Here, we describe an in vivo screen to interrogate the response to anthracycline-based chemotherapy in a syngeneic metastatic breast cancer model and identify JNK signaling as a key modulator of chemotherapy response. Combining in vitro and in vivo functional analyses, we demonstrate that JNK inhibition both promotes tumor cell cytostasis and blocks activation of the proapoptotic protein Bax, thereby antagonizing chemotherapy-mediated cytotoxicity. To investigate the clinical relevance of this dual role of JNK signaling, we developed a proliferation-independent JNK activity signature and demonstrate high JNK activity to be enriched in triple-negative and basal-like breast cancer subtypes. Consistent with the dual role of JNK signaling in vitro, high-level JNK pathway activation in triple-negative breast cancers is associated both with poor patient outcome in the absence of chemotherapy treatment and, in neoadjuvant clinical studies, is predictive of enhanced chemotherapy response. These data highlight the potential of monitoring JNK activity as early biomarker of response to chemotherapy and emphasize the importance of rational treatment regimes, particularly when combining cytostatic and chemotherapeutic agents. Mol Cancer Ther; 16(9); 1967-78. ©2017 AACR

Primary Care Staff's Views and Experiences Related to Routinely Advising Patients about Physical Activity. A Questionnaire Survey

Background: United Kingdom public health policy has recently re-emphasised the role of primary health care professionals in tackling increasing levels of physical inactivity within the general population. However, little is known about the impact that this has had in practice. This study explores Scottish primary care staff's knowledge, attitudes and experiences associated with advising patients about physical activity during routine consultations. Methods: A cross-sectional questionnaire survey of general practitioners (or family physicians), practice nurses and health visitors based in four health regions was conducted during 2004. The main outcome measures included: i) health professionals' knowledge of the current physical activity recommendations; (ii) practice related to routine physical activity advising; and (iii) associated attitudes. Results: Questionnaires were returned by 757 primary care staff (response rate 54%). Confidence and enthusiasm for giving advice was generally high, but knowledge of current physical activity recommendations was low. In general, respondents indicated that they routinely discuss and advise patients about physical activity regardless of the presenting condition. Health visitors and practice nurses were more likely than general practitioners to offer routine advice. Lack of time and resources were more likely to be reported as barriers to routine advising by general practitioners than other professional groups. However, health visitors and practice nurses were also more likely than general practitioners to believe that patients would follow their physical activity advice giving. Conclusion: If primary health care staff are to be fully motivated and effective in encouraging and supporting the general population to become more physically active, policymakers and health professionals need to engage in efforts to: (1) improve knowledge of current physical activity recommendations and population trends amongst frontline primary care staff; and (2) consider the development of tools to support individual assessment and advice giving to suit individual circumstances. Despite the fact that this study found that system barriers to routine advising were less of a problem than other previous research has indicated, this issue still remains a challenge

Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

BACKGROUND: Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. RESULTS: We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. CONCLUSIONS: Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly

In the Law We Trust; Some Thoughts on the ‘Legislative Gap’ in Legal Studies

The Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction

A snapshot of the prevalence of physical activity amongst older, community dwelling people in Victoria, Australia: patterns across the 'young-old' and 'old-old'

BACKGROUND: Physical activity has a range of health benefits for older people. The aim of this study was to determine physical activity prevalence and attitudes amongst respondents to a trial screening survey. METHODS: A cross-sectional survey was conducted. Subjects were community dwelling older people aged ≥ 65 years, recruited via general practices in Victoria, Australia. Participants completed a mailed screening tool containing the Geriatric Depression Scale, the Active Australia survey and the Physical Activity Readiness Questionnaire. RESULTS: Of 330 participants, 20% were ≥ 80 years. Activity levels were similar to those reported in population studies. The proportion of participants reporting physical activity was greatest for the walking category, but decreased across categories of physical activity intensity. The oldest-old were represented at all physical activity intensity levels. Over half reported exercising at levels that, according to national criteria are, 'sufficient to attain health benefit'. A greater proportion of participants aged 85 years and older were unaware of key physical activity messages, compared to participants aged less than 85 years. CONCLUSION: Most population surveys do not provide details of older people across age categories. This survey provided information on the physical activity of people up to 91 years old. Physical activity promotion strategies should be tailored according to the individual's needs. A better understanding of the determinants of physical activity behaviour amongst older sub-groups is needed to tailor and target physical activity promotion strategies and programs to maximise physical activity related health outcomes for older people

Health promotion in primary care: How should we intervene? A qualitative study involving both physicians and patients

<p>Abstract</p> <p>Background</p> <p>The effects of tobacco, physical exercise, diet, and alcohol consumption on morbidity and mortality underline the importance of health promotion and prevention (HPP) at the primary health care (PHC) level. Likewise, the deficiencies when putting such policies into practice and assessing their effectiveness are also widely recognised. The objectives of this research were: a) to gain an in-depth understanding of general practitioners' (GPs) and patients' perceptions about HPP in PHC, and b) to define the areas that could be improved in future interventions.</p> <p>Methods</p> <p>Qualitative methodology focussed on the field of health services research. Information was generated on the basis of two GP-based and two patient-based discussion groups, all of which had previously participated in two interventions concerning healthy lifestyle promotion (tobacco and physical exercise). Transcripts and field notes were analysed on the basis of a sociological discourse-analysis model. The results were validated by triangulation between researchers.</p> <p>Results</p> <p>GPs and patients' discourses about HPP in PHC were different in priorities and contents. An overall explanatory framework was designed to gain a better understanding of the meaning of GP-patient interactions related to HPP, and to show the main trends that emerged from their discourses. GPs linked their perceptions of HPP to their working conditions and experience in health services. The dimensions in this case involved the orientation of interventions, the goal of actions, and the evaluation of results. For patients, habits were mainly related to ways of life particularly influenced by close contexts. Health conceptions, their role as individuals, and the orientation of their demands were the most important dimensions in patients' sphere.</p> <p>Conclusions</p> <p>HPP activities in PHC need to be understood and assessed in the context of their interaction with the conditioning trends in health services and patients' social micro-contexts. On the basis of the explanatory framework, three development lines are proposed: the incorporation of new methodological approaches according to the complexity of HPP in PHC; the openness of habit change policies beyond the medical services; and the effective commitments in the medium to long term by the health services themselves at the policy management level.</p

Preventing disease through opportunistic, rapid engagement by primary care teams using behaviour change counselling (PRE-EMPT): protocol for a general practice-based cluster randomised trial

BACKGROUND: Smoking, excessive alcohol consumption, lack of exercise and an unhealthy diet are the key modifiable factors contributing to premature morbidity and mortality in the developed world. Brief interventions in health care consultations can be effective in changing single health behaviours. General Practice holds considerable potential for primary prevention through modifying patients' multiple risk behaviours, but feasible, acceptable and effective interventions are poorly developed, and uptake by practitioners is low. Through a process of theoretical development, modeling and exploratory trials, we have developed an intervention called Behaviour Change Counselling (BCC) derived from Motivational Interviewing (MI). This paper describes the protocol for an evaluation of a training intervention (the Talking Lifestyles Programme) which will enable practitioners to routinely use BCC during consultations for the above four risk behaviours. METHODS/DESIGN: This cluster randomised controlled efficacy trial (RCT) will evaluate the outcomes and costs of this training intervention for General Practitioners (GPs) and nurses. Training methods will include: a practice-based seminar, online self-directed learning, and reflecting on video recorded and simulated consultations. The intervention will be evaluated in 29 practices in Wales, UK; two clinicians will take part (one GP and one nurse) from each practice. In intervention practices both clinicians will receive training. The aim is to recruit 2000 patients into the study with an expected 30% drop out. The primary outcome will be the proportion of patients making changes in one or more of the four behaviours at three months. Results will be compared for patients seeing clinicians trained in BCC with patients seeing non-BCC trained clinicians. Economic and process evaluations will also be conducted. DISCUSSION: Opportunistic engagement by health professionals potentially represents a cost effective medical intervention. This study integrates an existing, innovative intervention method with an innovative training model to enable clinicians to routinely use BCC, providing them with new tools to encourage and support people to make healthier choices. This trial will evaluate effectiveness in primary care and determine costs of the intervention

What future, which technology? On the problem of describing relevant futures.

Doing research on future and emerging technologies raises a number of significant ontological and epistemological challenges. The fundamental uncertainty of the future, combined with problems of appropriate descriptions of technology in general, render it difficult to come to an appropriate account of the likely shape and use of future technologies. This paper discusses several streams of research that address this issue, including the question of relevant description and context, interpretive flexibility, affordances of technology, and multi-stability of technological trajectories. The paper proposes that some of these problems may be addressed by using a democratic and participative approach to technology research and development. Participative technology assessment is then discussed as an example of an established way of democratically engaging with technology stakeholders during research and development. The paper concludes by discussing the promises and limitations of such a participative approach with regard to the question of understanding and researching future technologies