Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE) and the U.S. National Institutes of Health (HD045784). None of the authors had any financial or personal conflicts of interest.Peer reviewedPostprin

Safe drive stay alive: Exploring effectiveness of a real-world driving intervention for predrivers and the utility of the health action process approach

Young drivers are greatly over-represented in road traffic collisions (RTCs) worldwide. Interventions attempt to change driving-related behaviours to reduce injuries and deaths from RTCs. The current study evaluated the effectiveness of the well-established Fife Safe Drive Stay Alive (SDSA) practice-based intervention on determinants of driving behaviour using the health action process approach (HAPA) model. Adolescent participants (predominantly predrivers) attending the SDSA intervention from schools and colleges in Fife, Scotland, were invited to complete an evaluation at baseline and at 3 months exploring motivational determinants of driving behaviour (eg, risk perception). Intervention content was examined for behaviour change techniques (BCTs). Eighty-seven participants completed both baseline and follow-up evaluations. The motivational HAPA model variables predicted driving intentions. There was no significant overall effect of the SDSA intervention between baseline and 3-month follow-up. Seven negatively framed BCTs were used in the intervention. The effectiveness of SDSA is questioned; however, the study supports the use of the HAPA model in explaining driving intentions, and therefore, may usefully inform driving interventions

Modeling the pore structure of voltage-gated sodium channels in closed, open, and fast-inactivated conformation reveals details of site 1 toxin and local anesthetic binding

In this work molecular modeling was applied to generate homology models of the pore region of the Na v 1.2 and Na v 1.8 isoforms of human voltage-gated sodium channels. The models represent the channels in the resting, open, and fast-inactivated states. The transmembrane portions of the channels were based on the equivalent domains of the closed and open conformation potassium channels KcsA and MthK, respectively. The critical selectivity loops were modeled using a structural template identified by a novel 3D-search technique and subsequently merged with the transmembrane portions. The resulting draft models were used to study the differences of tetrodotoxin binding to the tetrodotoxin-sensitive Na v 1.2 (EC50: 0.012μM) and -insensitive Na v 1.8 (EC50: 60μM) isoforms, respectively. Furthermore, we investigated binding of the local anesthetic tetracaine to Na v 1.8 (EC50: 12.5μM) in resting, conducting, and fast-inactivated state. In accordance with experimental mutagenesis studies, computational docking of tetrodotoxin and tetracaine provided (1) a description of site 1 toxin and local anesthetic binding sites in voltage-gated sodium channels. (2) A rationale for site 1 toxin-sensitivity versus -insensitivity in atomic detail involving interactions of the Na v 1.2 residues F385-I and W943-II. (3) A working hypothesis of interactions between Na v 1.8 in different conformational states and the local anesthetic tetracaine. Figure Tetracaine in complex with Nav1.8 in fast-inactivated form. The ligand is represented in CPK and colored by atom type. Ribbons and amino acids are colored by domain: yellow = domain I, blue = domain II, green = domain III, red = domain IV, pink = inactivation gate. Main interaction partners are shown in CPK. a) Tetracaine bound to the inner vestibule. View along the membrane plane. b) Same view as in a but limited to main interaction partners only. The polar head group of tetracaine interacts with the DEKA-motif residues, its hydrophobic tail with the hydrophobic and mainly aromatic residues of S6-IV and the inactivation gat

Partnership work between Public Health and Health Psychology: introduction to a novel training programme

Background: Public health services implement individual, community and population level interventions to change health behaviours, improve healthy life expectancy and reduce health inequalities. Understanding and changing health behaviour is complex. Integrating behaviour change theory and evidence into interventions has the potential to improve services. Methods: Health Psychologists apply evidence and theories aimed at understanding and changing health behaviour. A Scottish programme is piloting the training of Health Psychologists within NHS contexts to address prominent public health challenges. Results: This article outlines the details of this novel programme. Two projects are examined to illustrate the potential of partnership working between public health and health psychology. Conclusion: In order to develop and improve behaviour change interventions and services, public health planners may want to consider developing and using the knowledge and skills of Health Psychologists. Supporting such training within public health contexts is a promising avenue to build critical NHS internal mass to tackle the major public health challenges ahead

Community end-of-life care during the COVID-19 pandemic: findings of a UK primary care survey.

BACKGROUND: Thousands of people in the UK have required end-of-life care in the community during the COVID-19 pandemic. Primary healthcare teams (general practice and community nursing services) have provided the majority of this care, alongside specialist colleagues. There is a need to learn from this experience in order to inform future service delivery and planning. AIM: To understand the views of GPs and community nurses providing end-of-life care during the first wave of the COVID-19 pandemic. DESIGN & SETTING: A web-based, UK-wide questionnaire survey circulated via professional general practice and community nursing networks, during September and October 2020. METHOD: Responses were analysed using descriptive statistics and an inductive thematic analysis. RESULTS: Valid responses were received from 559 individuals (387 community nurses, 156 GPs, and 16 unspecified roles), from all regions of the UK. The majority reported increased involvement in providing community end-of-life care. Contrasting and potentially conflicting roles emerged between GPs and community nurses. There was increased use of remote consultations, particularly by GPs. Community nurses took greater responsibility in most aspects of end-of-life care practice, particularly face-to-face care, but reported feeling isolated. For some GPs and community nurses, there has been considerable emotional distress. CONCLUSION: Primary healthcare services are playing a critical role in meeting increased need for end-of-life care in the community during the COVID-19 pandemic. They have adapted rapidly, but the significant emotional impact, especially for community nurses, needs addressing alongside rebuilding trusting and supportive team dynamics

Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients

Background: Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer.Findings: Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF beta 1 also showed no difference.Conclusions: The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach

Characterising radium-226 particles from legacy contamination to support radiation dose assessments

Radioactive particles are physically discrete sources of radioactivity that have been released into the environment as a result of past emergencies, events and practices. As the release of radioactive particles is often unplanned, the source term has not been characterised, and the potential radiation doses have not been prospectively assessed. If a plausible exposure pathway exists, radioactive particles in the environment may present a hazard to the public depending on their radiological, physical and chemical characteristics. Given their physically discrete nature, standard assessment approaches such as dispersion and transfer modelling of liquid and gaseous radioactive releases, are not appropriate for radioactive particles. The challenge for national regulatory authorities is to calculate potential radiation doses from unplanned releases of radioactive particles into the environment, assess whether the doses are relevant to radiological protection and decide whether actions are required to reduce potential doses. To address this challenge, this paper presents the approach being adopted to radiologically, physically and chemically characterise Ra-226 particles from a contaminated legacy site using gamma spectrometry, optical macroscopy and SEM-EDS. The use of particle characterisation data to support radiation dose assessments is discussed and consideration is given to radioactive particles in the context of radiological protection