Nerve growth factor (NGF), a trophic factor involved in the development, maintenance, and survival of the peripheral nervous system and the cholinergic neurons of the central nervous system, is significantly reduced in Alzheimer's Disease (AD) patients (Aloe et al., 2012). Particularly basal forebrain complex (BFC) neurons are highly affected in AD patients. NGF protects BFC neurons in experimental trauma models and in age-associated cholinergic decline. Therefore, administration of NGF is investigated as a therapeutic option for AD patients (Aloe et al., 2012). NGF therapy is limited by hyperalgesia, limited bioavailability, and use of invasive methods including intracranial injection of adeno-associated virus-based gene delivery vector, which constitutively expresses human NGF. In this context, non-pharmacological modes of treatment such as meditation and Yoga have been considered as alternative approaches to treat neurological disorders. Yogic breathing (YB, also called Pranayama) is a collection of techniques to regulate breathing voluntarily. YB induces a strong relaxation response via vagal and parasympathetic stimulation (Jerath et al., 2006). Such responses are causally linked to rapid changes in gene expression, particularly to those genes controlling stress, inflammation, and metabolism. Saliva is a known source of NGF, and incidentally, Yoga and relaxation stimulate salivation. Saliva (0.75–1.5 L/day in humans) contains numerous biologically active molecules to be potentially useful as diagnostic markers and as therapeutic clues. Salivary secretion regulates the digestive, nervous, immune, and respiratory systems. We conducted a pilot study to investigate whether YB could potentially stimulate salivary expression of NGF in cognitively normal healthy volunteers. This could serve as a model for future studies in AD patients.
PurposeThe purpose of this study is to report how the palliative and end of life care community in one region of England worked together to create a new model for integrated palliative and end of life care to respond to the challenges of changing demography, the need to reduce unnecessary hospital admissions of people nearing the end of life and to improve the quality of provision in line with current policy.Design/methodology/approachA co-production approach to system transformation was adopted involving 73 members of the palliative and end of life care community in one region of England.FindingsA new model for the delivery of integrated palliative and end of life care services was produced. The breadth of membership of the co-production working party and constructive/collaborative working helped ensure a viable model was produced.Practical implicationsAlthough systems’ thinking perspectives can help address the challenges of large-scale transformation because they focus on promoting the value of relationships, recognise the nuances of context and the need to understand system behaviour over time, the potential for systems to benefit from this approach is limited by the complexity of the processes involved and the sheer number of issues to be addressed in practical terms by policy makers and change leaders.Originality/valueThe paper explores the contribution that theories of large-scale transformation can make to the design of palliative and end of life care services in health and social care.
During prolonged hypertrophic insult to the myocardium, while the function of cardiomyocytes needs to be protected, the hyperactivation of cardiac fibroblasts has to be curbed to prevent fibrosis. Previously, we showed that integrin-mediated non-receptor tyrosine kinase (NRTK) activation is required for normal functioning of both cardiac fibroblasts and cardiomyocytes. We hypothesized that inhibition of NRTKs in cardiac fibroblasts without affecting cardiomyocytes would be beneficial to the stressed myocardium. Our initial studies using kinase inactive forms of Src, Pyk2 and FAK expressed adenovirally in isolated primary cardiac fibroblasts showed that the pro-fibrotic signaling events as studied by fibronectin and collagen deposition are downregulated. Our in vivo studies in mouse transverse aortic constriction (TAC) model suggest that dasatinib, a multikinase NRTK inhibitor administration via a peritoneally implanted mini-osmotic pump is able to preserve ventricular geometry and function and reduce the accumulation of fibrotic extracellular matrix (ECM) proteins upon 4 wk pressure overload. Data obtained from cell culture experiments with kinase inactive NRTKs and dasatinib suggest that NRTK inhibition is able to reduce the proliferation, migration and mitogenic signaling in cardiac fibroblasts without affecting the cell survival pathways in cardiomyocytes. These data indicate that NRTKs play a significant pro-fibrotic role in cardiac fibroblasts and curbing the activity of NRTKs could be a potential therapeutic approach to treat fibrosis in hypertrophic heart diseases.
Introduction Palliative care nurses who have been traditionally caring for patients with cancer (CP) have started to care for non-cancer patients (NCP) as specialist hospice environments are broadening their patient criteria to accept a range of non-malignant conditions outside of cancer within the UK. Aim The overarching aim of this qualitative research study is to explore the perceptions of registered nurses working in a hospice in Staffordshire, caring for NCPs. Specifically this involved: exploring how confident nurses feel while caring for NCPs; identifying and describing the similarities and differences when caring for this population and those with cancer; highlighting the educational needs related to understanding the natural history of symptoms and problems in non-cancer patients; and recognising nursing perceptions on what supports/disables confidence in caring for patients with a non-malignant disease. Method Focus groups were conducted in this qualitative research study (n=8; n=8). The discussions were digitally recorded, transcribed verbatim and analysed using content/thematic analysis. Results Five key themes evolved from the research, namely: the importance of preparation; the differences and similarities between treating NCPs and CPs; the importance of collaborative working was crucial; staff and patient perspectives; and the associated challenges in terms of time, skills needed and interestingly, what the future holds for NCPs within the hospice context. Conclusions Focus groups were used successfully to explore perceptions of registered nurses around caring for NCP within one hospice environment within the UK. While there were many challenges and tensions identified, these were well balanced with the tensions of positive and constructive comments around the integration of patients with non-malignant diseases within a traditionally cancer driven organisation. Such a change in direction will impact upon how staff manage this within existing palliative and end of life care provision.
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