Identification of caspase 3 motifs and critical aspartate residues in human Phospholipase D1b and Phopsholipase D2a

Stimulation of mammalian cells frequently initiates phospholipase D-catalysed hydrolysis of phosphatidylcholine in the plasma membrane to yield phosphatidic acid (PA) a novel lipid messenger. PA plays a regulatory role in important cellular processes such as secretion, cellular shape change and movement. A number of studies have highlighted that PLD-based signalling also plays a pro-mitogenic and pro-survival role in cells and therefore anti-apoptotic. We show that human PLD1b and PLD2a contain functional caspase-3 cleavage sites and identify the critical aspartate residues within PLD1b that affect its activation by phorbol esters and attenuate phosphatidylcholine hydrolysis during apoptosis

Putting Life in Years (PLINY): a randomised controlled trial and mixed-methods process evaluation of a telephone friendship intervention to improve mental well-being in independently living older people

YesBackground: Social isolation in older adults is associated with morbidity. Evaluating interventions to promote social engagement is a research priority. Methods: A parallel-group randomised controlled trial was planned to evaluate whether telephone friendship (TF) improves the well-being of independently living older people. An internal pilot aimed to recruit 68 participants by 30 September 2012, with 80% retained at 6 months. Randomisation was web based and only analysts were blind to allocation. A service provider was contracted to train 10 volunteer facilitators by 1 April 2012 and 10 more by 1 September 2012. Participants were aged > 74 years with good cognitive function and living independently in an urban community. The intervention arm of the trial consisted of manualised TF with standardised training: (1) one-to-one befriending (10- to 20-minute calls once per week for up to 6 weeks made by volunteer facilitators) followed by (2) TF groups of six participants (1-hour teleconferences once per week for 12 weeks facilitated by the same volunteer). Friendship groups aimed to enhance social support and increase opportunities for social interaction to maintain well-being. This was compared with usual health and social care provision. The primary clinical outcome was the Short Form questionnaire-36 items (SF-36) mental health dimension score at 6 months post randomisation. Qualitative research assessing intervention acceptability (participants) and implementation issues (facilitators) and an intervention fidelity assessment were also carried out. Intervention implementation was documented through e-mails, meeting minutes and field notes. Acceptability was assessed through framework analysis of semistructured interviews. Two researchers coded audio recordings of telephone discussions for fidelity using a specially designed checklist. Results: In total, 157 people were randomised to the TF group (n = 78) or the control group (n = 79). Pilot recruitment and retention targets were met. Ten volunteers were trained by 1 September 2012; after volunteer attrition, three out of the 10 volunteers delivered the group intervention. In total, 50 out of the 78 TF participants did not receive the intervention and the trial was closed early. A total of 56 people contributed primary outcome data from the TF (n = 26) and control (n = 30) arms. The mean difference in SF-36 mental health score was 9.5 (95% confidence interval 4.5 to 14.5) after adjusting for age, sex and baseline score. Participants who were interviewed (n = 19) generally declared that the intervention was acceptable. Participant dissatisfaction with closure of the groups was reported (n = 4). Dissatisfaction focused on lack of face-to-face contact and shared interests or attitudes. Larger groups experienced better cohesion. Interviewed volunteers (n = 3) expressed a lack of clarity about procedures, anxieties about managing group dynamics and a lack of confidence in the training and in their management and found scheduling calls challenging. Training was 91–95% adherent with the checklist (39 items; three groups). Intervention fidelity ranged from 30.2% to 52.1% (28–41 items; three groups, three time points), indicating that groups were not facilitated in line with training, namely with regard to the setting of ground rules, the maintenance of confidentiality and facilitating contact between participants. Conclusions: Although the trial was unsuccessful for a range of logistical reasons, the experience gained is of value for the design and conduct of future trials. Participant recruitment and retention were feasible. Small voluntary sector organisations may be unable to recruit, train and retain adequate numbers of volunteers to implement new services at scale over a short time scale. Such risks might be mitigated by multicentre trials using multiple providers and specialists to recruit and manage volunteers.Funding for this study was provided by the Public Health Research programme of the National Institute for Health Research

A feasibility study for NOn-Traditional providers to support the management of Elderly People with Anxiety and Depression: the NOTEPAD study Protocol

BACKGROUND: Anxiety and depression are common among older people, with up to 20% reporting such symptoms, and the prevalence increases with co-morbid chronic physical health problems. Access to treatment for anxiety and depression in this population is poor due to a combination of factors at the level of patient, practitioner and healthcare system. There is evidence to suggest that older people with anxiety and/or depression may benefit both from one-to-one interventions and group social or educational activities, which reduce loneliness, are participatory and offer some activity. Non-traditional providers (support workers) working within third-sector (voluntary) organisations are a valuable source of expertise within the community but are under-utilised by primary care practitioners. Such a resource could increase access to care, and be less stigmatising and more acceptable for older people. METHODS: The study is in three phases and this paper describes the protocol for phase III, which will evaluate the feasibility of recruiting general practices and patients into the study, and determine whether support workers can deliver the intervention to older people with sufficient fidelity and whether this approach is acceptable to patients, general practitioners and the third-sector providers. Phase III of the NOTEPAD study is a randomised controlled trial (RCT) that is individually randomised. It recruited participants from approximately six general practices in the UK. In total, 100 participants aged 65 years and over who score 10 or more on PHQ9 or GAD7 for anxiety or depression will be recruited and randomised to the intervention or usual general practice care. A mixed methods approach will be used and follow-up will be conducted 12 weeks post-randomisation. DISCUSSION: This study will inform the design and methods of a future full-scale RCT. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN16318986 . Registered 10 November 2016. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN

Loneliness and biological responses to acute stress in people with Type 2 diabetes

Loneliness is linked with all-cause mortality and coronary heart disease. Altered neuroendocrine and inflammatory responses to stress constitute potential pathways linking loneliness and ill-health. Stress responsivity is modified in people with Type 2 diabetes, but it is unclear whether loneliness influences biological stress responses in this population. We assessed interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), monocyte chemoattractant protein-1 (MCP-1), and cortisol responses to acute stress in 135 people with Type 2 diabetes. Loneliness was measured used the Revised UCLA Loneliness Scale. Loneliness was inversely associated with cortisol output poststress (B = -4.429, p = 0.019) independent of age, sex, education, marital status, body mass index, and smoking. Lonelier individuals had raised MCP-1 concentrations 75 min poststress independent of covariates (B = 0.713, p = 0.022). No associations between loneliness and IL-6 or IL-1RA concentrations were detected. These results suggest that loneliness is associated with disturbances in stress responsivity in people with diabetes, and the impact of loneliness on health in people with diabetes may be mediated in part through dysregulation of inflammatory and neuroendocrine systems. Future research is required to understand if such changes increase the risk of poorer outcomes in this population

Provision of private practice as a learning environment for midwifery students

The availability of midwifery led continuity of care models within health services or via home birth with a known midwife creates an opportunity for midwifery students to be placed with midwives to experience continuity of care for women in such models. In some States and Territories of Australia, however not Queensland, midwifery led continuity of care models including home birth are available through public health services.The literature is clear that home birth for low risk women is a viable and safe choice for women (The National Institute for Health Care and Excellence, 2014). It is suggested midwifery students undertake clinical experience with planned home birth (Vedam et al., 2009). CQUniversity was offered placements for midwifery students in midwifery models of care that included home birth. However, CQUniversity was unable to secure indemnity insurance to cover midwifery students for the intra-partum care component at home in these placements.Research via a quantitative survey to investigate options for midwifery students to undertake clinical placement with independent practicing midwives attending home births was undertaken. This research was to ascertain if universities within Australia provided clinical placement for midwifery students in planned home birth and if so what indemnity insurance arrangements were in place. This presentation will explore the issue, disseminate the findings of the research undertaken and discuss a governance plan. This research has implications for educators in midwifery programs nationally

Provision of private practice as a learning environment for midwifery students

The availability of midwifery led continuity of care models within health services or via home birth with a known midwife creates an opportunity for midwifery students to be placed with midwives to experience continuity of care for women in such models. In some States and Territories of Australia, however not Queensland, midwifery led continuity of care models including home birth are available through public health services.The literature is clear that home birth for low risk women is a viable and safe choice for women (The National Institute for Health Care and Excellence, 2014). It is suggested midwifery students undertake clinical experience with planned home birth (Vedam et al., 2009). CQUniversity was offered placements for midwifery students in midwifery models of care that included home birth. However, CQUniversity was unable to secure indemnity insurance to cover midwifery students for the intra-partum care component at home in these placements.Research via a quantitative survey to investigate options for midwifery students to undertake clinical placement with independent practicing midwives attending home births was undertaken. This research was to ascertain if universities within Australia provided clinical placement for midwifery students in planned home birth and if so what indemnity insurance arrangements were in place. This presentation will explore the issue, disseminate the findings of the research undertaken and discuss a governance plan. This research has implications for educators in midwifery programs nationally