To branch or to expand?

Oscillating protein signals control the branching and expansion of blood vessels

Improving living and dying for people with advanced dementia living in care homes: a realist review of Namaste Care and other multisensory interventions

© The Author(s). 2018Background: Seventy percent of people with advanced dementia live and die in care homes. Multisensory approaches, such as Namaste Care, have been developed to improve the quality of life and dying for people with advanced dementia but little is known about effectiveness or optimum delivery. The aim of this review was to develop an explanatory account of how the Namaste Care intervention might work, on what outcomes, and in what circumstances. Methods: This is a realist review involving scoping of the literature and stakeholder interviews to develop theoretical explanations of how interventions might work, systematic searches of the evidence to test and develop the theories, and their validation with a purposive sample of stakeholders. Twenty stakeholders - user/patient representatives, dementia care providers, care home staff, researchers -took part in interviews and/or workshops. Results: We included 85 papers. Eight focused on Namaste Care and the remainder on other types of sensory interventions such as music therapy or massage. We identified three context-mechanism-outcome configurations which together provide an explanatory account of what needs to be in place for Namaste Care to work for people living with advanced dementia. This includes: providing structured access to social and physical stimulation, equipping care home staff to cope effectively with complex behaviours and variable responses, and providing a framework for person-centred care. A key overarching theme concerned the importance of activities that enabled the development of moments of connection for people with advanced dementia. Conclusions: This realist review provides a coherent account of how Namaste Care, and other multisensory interventions might work. It provides practitioners and researchers with a framework to judge the feasibility and likely success of Namaste Care in long term settings. Key for staff and residents is that the intervention triggers feelings of familiarity, reassurance, engagement and connection.Peer reviewe

A mathematical model separates quantitatively the cytostatic and cytotoxic effects of a HER2 tyrosine kinase inhibitor

BACKGROUND: Oncogene signaling is known to deregulate cell proliferation resulting in uncontrolled growth and cellular transformation. Gene amplification and/or somatic mutations of the HER2/Neu (ErbB2) proto-oncogene occur in approximately 20% of breast cancers. A therapeutic strategy that has been used to block HER2 function is the small molecule tyrosine kinase inhibitor lapatinib. Using human mammary epithelial cells that overexpress HER2, we determined the anti-proliferative effect of lapatinib through measuring the total cell number and analyzing the cell cycle distribution. A mathematical model was used to interpret the experimental data. RESULTS: The model suggests that lapatinib acts as expected by slowing the transition through G(1 )phase. However, the experimental data indicated a previously unreported late cytotoxic effect, which was incorporated into the model. Both effects depend on the dosage of the drug, which shows saturation kinetics. CONCLUSION: The model separates quantitatively the cytostatic and cytotoxic effects of lapatinib and may have implications for preclinical studies with other anti-oncogene therapies

Classroom Management System Via Mobile Devices

Mobile devices, applications and services become assimilated into people’s daily activities. The full potential of mobile application is realized when people can access current information at anytime and at anywhere. Existing practice in allocating available classrooms and classrooms reservation are performed manually. In addition, to report any device failure located in classrooms is currently made by calling the helpdesk. Therefore, a Classroom Management System (CMS) via mobile devices is proposed to overcome such problems; allowing lecturers to identify the required classrooms,perform classroom reservation and find the person-in-charge while administration staffs can operate on managing the rooms. System Development Research Methodology(SDRM) has been used for the CMS development. Users acceptance towards CMS had been identified by performing a field study involving 15 respondents. Results showed that 75% of the respondents are satisfied with CMS and felt that it is an acceptable application. Hence, this indicates that CMS provides satisfaction to lecturers and administration staffs in facilitating the daily routine of their working environmen

A phase II study of Yondelis® (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer

Yondelis® (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m−2 was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36–67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88–15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens

The outcomes of a person-centered, non-pharmacological intervention in reducing agitation in residents with dementia in Australian rural nursing homes

Background: There is limited best- practice evidence to address behavioral and psychiatric symptoms for those with dementia in Australian rural nursing homes. This study aims to evaluate the outcomes of a person-centered, non-pharmacological dementia care model, ‘Harmony in the Bush’, based on the Progressively Lowered Stress Threshold principles and person-centered music in rural Australia. Methods: A quasi-experimental (nonrandomized, pre-post) intervention study was conducted in five rural nursing homes in Queensland and South Australia. Seventy-four residents with dementia participated in this intervention study, which yielded a sample power of 80%. Eighty-seven staff completed the Caregiver Stress Inventory at pre-post four-weeks of intervention. Staff training workshops focused on the theory of the Progressively Lowered Stress Threshold principles and delivery of person-centered care plan with integrated music intervention. We used reported changes in agitation of the residents, measured using Cohen- Mansfield Agitation Inventory, and staff’s caregiving stress, using Caregivers Stress Inventory. This study adheres to the CONSORT guidelines. Results: Mean age of residents with dementia was 82.4 (7.7) years and 69% were females. The mean age of admission was 80.1(8.4) years. Baseline measures indicated that 32.7% had mild- severe pain and 30.5% reported mild-severe sadness. The results showed statistically significant decline in aggressive behaviors, physically non-aggressive behaviors, verbally agitated behavior and hiding and hoarding. There was similar reduction in staff stress in the domains of aggressive behaviors, inappropriate behaviors, resident safety, and resource deficiency. Conclusions: The Harmony in the Bush model is effective in reducing agitation among dementia residents with significant reduction in staff stress levels in nursing homes in rural Australia. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR) on 20/2/2018 (Registration No: ACTRN12618000263291p). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374458

Individual music therapy for managing neuropsychiatric symptoms for people with dementia and their carers: a cluster randomised controlled feasibility study

Background: Previous research highlights the importance of staff involvement in psychosocial interventions targeting neuropsychiatric symptoms of dementia. Music therapy has shown potential effects, but it is not clear how this intervention can be programmed to involve care staff within the delivery of patients’ care. This study reports initial feasibility and outcomes from a five month music therapy programme including weekly individual active music therapy for people with dementia and weekly post-therapy video presentations for their carers in care homes. Methods: 17 care home residents and 10 care staff were randomised to the music therapy intervention group or standard care control group. The cluster randomised, controlled trial included baseline, 3-month, 5-month and post-intervention 7-month measures of residents’ symptoms and well-being. Carer-resident interactions were also assessed. Feasibility was based on carers’ feedback through semi-structured interviews, programme evaluations and track records of the study. Results: The music therapy programme appeared to be a practicable and acceptable intervention for care home residents and staff in managing dementia symptoms. Recruitment and retention data indicated feasibility but also challenges. Preliminary outcomes indicated differences in symptoms (13.42, 95 % CI: [4.78 to 22.07; p = 0.006]) and in levels of wellbeing (−0.74, 95 % CI: [−1.15 to −0.33; p = 0.003]) between the two groups, indicating that residents receiving music therapy improved. Staff in the intervention group reported enhanced caregiving techniques as a result of the programme. Conclusion: The data supports the value of developing a music therapy programme involving weekly active individual music therapy sessions and music therapist-carer communication. The intervention is feasible with modifications in a more rigorous evaluation of a larger sample size

Novel molecular and pharmacological regulators of Neural Stem Cells in physiological and disease mechanisms

Neural Stem Cells (NSC) perform a very important role during brain development as they are involved in the formation of the main neuronal circuitry contributing to the entire brain structural and functional formation. These cells persist even in discrete regions of adult mammalian brain such as the subgranular zone of the dentate gyrus. In the adult hippocampus, NSC and newborn neurons confer an extra degree of neural plasticity, which likely contributes to crucial brain functions such as learning, memory and mood regulation. Alteration in NSC properties, principally proliferation and neuronal differentiation, during brain development stage could strongly affect brain formation. In fact, patients with the Down syndrome (DS), a neurodevelopmental disorder due to chromosome 21 trisomy, show a reduced NSC proliferation and neurogenesis before prenatal stage and important deficits in higher cognitive functions, such as learning and memory. It was demonstrated in animal model that early treatments could restore neural defect in DS. In such respect, we want to identify novel clinically relevant drugs that could modulate neonatal neurogenesis with the aim to develop the potential therapies for DS patients. However, deregulation of neurogenesis in adult brain has even been demonstrated in several neurodegenerative disorders, including the major depression. Major depression is one of the areas where adult hippocampal neurogenesis is extensively studied. Several preclinical studies indicate that chronic administration of antidepressant drugs results in enhanced neurogenesis in the adult rodent and human DG. This opens the possibility that modulation of adult neurogenesis may contribute to the therapeutic effects of these drugs also in the clinical setting. However, it is unknown the contribution of different serotoninergic receptors in the proneurogenic effect mediated by antidepressants. In such respect, we investigate in detail the role of serotonin signalling in the regulation of adult hippocampal neurogenesi

Adult hippocampal neural progenitor cells: an Important In vitro tool for studying complex mechanisms regulating adult neurogenesis

Adult hippocampal neurogenesis (ahNG) is a peculiar form of neural plasticity involved in crucial brain functions including cognition, mood and stress response. Adult hippocampal neural progenitor cells (ahNPC) differentiation is modulated positively or negatively by several factors. Understanding the mechanisms regulating ahNG will shed light on its role in brain physiopathology. Astrocytes, one of the major component of the neurogenic niche, might regulate ahNPC fate specification. Little is known about the identity of astrocytes-secreted proteins and the subcellular mechanisms mediating their modulatory effect. Interestingly ahNG is deregulated in neuropsychiatric disorders such as major depression. The specific involvement of serotonin (5-HT) receptors family in mediating antidepressants (AD) effect add more complication into serotonin role in depression and is still not extensively described. Several studies documented a role of NF-\uf06bB signaling in ahNPC response to proneurogenic molecules. Yet scarce data described how the knockout of NF-\uf06bB p50 subunit (p50KO) could affect ahNG. In vitro analysis of astrocytes conditioned media (ACM) effect on ahNPC differentiation, showed that p50 absence induced intrinsic and extrinsic defects in both cell types. These results could explain earlier study published in our group showing that p50KO mice have reduced ahNG and severe deficits in hippocampal-dependent cognitive performance. Moreover, lipocalin-2 (LCN-2) was identified as a novel astrocyte-derived proneurogenic signal. In the second part of the study we showed that 5-HT2A/2C receptors antagonism and 5-HT7 activation are proneurogenic on ahNPC. Moreover NF-B p50 subunit presence was required for the multimodal AD induced increase of neurogenesis. In conclusion, ahNPC modulation by astrocyte-released factors and serotonin receptors might be future pharmacological targets for increasing ahNG specifically in neurodegenerative and neuropsychiatric disorders

Caring for Individuals with Dementia on a Continuum: An Interdisciplinary Approach Between Music Therapy and Nursing

Background: Music has long been used to ease symptoms of dementia. Several studies have shown the therapeutic benefits of music therapy to decrease symptoms of agitation in people with dementia (PWD). Other research has demonstrated that the use of music during caregiving can ease agitated behaviors. However, few studies have shown the clinical benefits of using translational research in practice between music therapists and certified nursing assistants