Co-morbidity and polypharmacy in Parkinson's Disease:insights from a large Scottish primary care database

Background: Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease across 31 other physical, and seven mental health conditions. Methods: We analysed primary health-care data on 510,502 adults aged 55 and over. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated age, sex and deprivation adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for those with PD compared to those without, for the prevalence, and number of conditions. Results: Two thousand six hundred forty (0.5%) had Parkinson’s disease, of whom only 7.4% had no other conditions compared with 22.9% of controls (adjusted OR [aOR] 0.43, 95% 0.38–0.49). The Parkinson’s group had more conditions, with the biggest difference found for seven or more conditions (PD 12.1% vs. controls 3.9%; aOR 2.08 95% CI 1.84–2.35). 12 of the 31 physical conditions and five of the seven mental health conditions were significantly more prevalent in the PD group. 44.5% with Parkinson’s disease were on five to nine repeat prescriptions compared to 24.5% of controls (aOR 1.40; 95% CI 1.28 to 1.53) and 19.2% on ten or more compared to 6.2% of controls (aOR 1.90; 95% CI 1.68 to 2.15). Conclusions: Parkinson’s disease is associated with substantial physical and mental co-morbidity. Polypharmacy is also a significant issue due to the complex nature of the disease and associated treatments

Crisis resolution and home treatment in the UK: A survey of model fidelity using a novel review methodology

Crisis resolution teams (CRTs) provide treatment at home to people experiencing mental health crises, as an alternative to hospital admission. Previous UK research, based on self‐report surveys, suggests that a loosely specified model has resulted in wide variations in CRTs’ service delivery, organization and outcomes. A fidelity scale (developed through evidence review and stakeholder consensus) provided a means of objectively measuring adherence to a model of good practice for CRTs, via one‐day fidelity reviews of UK crisis teams. Reviews included interviews with service users, carers, staff and managers, and examination of data, policies, protocols and anonymized case notes. Of the 75 teams reviewed, 49 (65%) were assessed as being moderate fidelity and the rest as low fidelity, with no team achieving high fidelity. The median score was 122 (range: 73–151; inter‐quartile range: 111–132). Teams achieved higher scores on items about structure and organization, for example ease of referral, medication and safety systems, but scored poorly on items about the content of care and interventions. Despite a national mandate to implement the CRT model, there are wide variations in implementation in the UK and no teams in our sample achieved overall high fidelity. This suggests that a mandatory national policy is not in itself sufficient to achieve good quality implementation of a service model. The CRT Fidelity Scale provides a feasible and acceptable means to objectively assess model fidelity in CRTs. There is a need for development and testing of interventions to enhance model fidelity and facilitate improvements to these services

Cross-sectional associations between personality traits and device-based measures of step count and sedentary behaviour in older age: the Lothian Birth Cohort 1936

Background: While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age. Methods: We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2. Results: None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps &gt;.07). Conclusions: We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.</p

Functional analysis of the rodent CK1tau mutation in the circadian clock of a marine unicellular alga

BACKGROUND: Casein Kinase 1 (CK1) is one of few proteins known to affect cellular timekeeping across metazoans, and the naturally occurring CK1(tau) mutation shortens circadian period in mammals. Functional conservation of a timekeeping function for CK1 in the green lineage was recently identified in the green marine unicell Ostreococcus tauri, in spite of the absence of CK1's transcriptional targets known from other species. The short-period phenotype of CK1(tau) mutant in mammals depends specifically on increased CK1 activity against PERIOD proteins. To understand how CK1 acts differently upon the algal clock, we analysed the cellular and proteomic effects of CK1(tau) overexpression in O. tauri. RESULTS: Overexpression of the CK1(tau) in O. tauri induces period lengthening identical to overexpression of wild-type CK1, in addition to resistance to CK1 inhibitor IC261. Label-free quantitative mass spectrometry of CK1(tau) overexpressing algae revealed a total of 58 unique phospho-sites that are differentially responsive to CK1(tau). Combined with CK1 phosphorylation site prediction tools and previously published wild-type CK1-responsive peptides, this study results in a highly stringent list of upregulated phospho-sites, derived from proteins containing ankyrin repeats, kinase proteins, and phosphoinositide-binding proteins. CONCLUSIONS: The identical phenotype for overexpression of wild-type CK1 and CK1(tau) is in line with the absence of critical targets for rodent CK1(tau) in O. tauri. Proteomic analyses reveal that two thirds of previously reported CK1 overexpression-responsive phospho-sites are shared with CK1(tau). These results indicate that the two alleles are functionally indiscriminate in O. tauri, and verify the identified cellular CK1 target proteins in a minimal circadian model organism

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Label-free quantitative analysis of the casein kinase 2-responsive phosphoproteome of the marine minimal model species Ostreococcus tauri

Casein kinase 2 (CK2) is a protein kinase that phosphorylates a plethora of cellular target proteins involved in processes including DNA repair, cell cycle control, and circadian timekeeping. CK2 is functionally conserved across eukaryotes, although the substrate proteins identified in a range of complex tissues are often different. The marine alga Ostreococcus tauri is a unicellular eukaryotic model organism ideally suited to efficiently study generic roles of CK2 in the cellular circadian clock. Overexpression of CK2 leads to a slow circadian rhythm, verifying functional conservation of CK2 in timekeeping. The proteome was analysed in wild‐type and CK2‐overexpressing algae at dawn and dusk, revealing that differential abundance of the global proteome across the day is largely unaffected by overexpression. However, CK2 activity contributed more strongly to timekeeping at dusk than at dawn. The phosphoproteome of a CK2 overexpression line and cells treated with CK2 inhibitor was therefore analysed and compared to control cells at dusk. We report an extensive catalogue of 447 unique CK2‐responsive differential phosphopeptide motifs to inform future studies into CK2 activity in the circadian clock of more complex tissues. All MS data have been deposited in the ProteomeXchange with identifier PXD000975 (http://proteomecentral.proteomexchange.org/dataset/PXD000975)

Interdisciplinary working in public health research: a proposed good practice checklist.

Background: Guidance on how different disciplines from the natural, behavioural and social sciences can collaborate to resolve complex public health problems is lacking. This article presents a checklist to support researchers and principle investigators to develop and implement interdisciplinary collaborations. Methods: Fourteen individuals, representing 10 disciplines, participated in in-depth interviews to explore the strengths and challenges of working together on an interdisciplinary project to identify the determinants of substance use and gambling disorders, and to make recommendations for future interdisciplinary teams. Data were analysed thematically and a checklist was derived from insights offered by participants during interview and discussion among the authors on the implications of findings. Results: Participants identified 18 scientific, interactional and structural strengths and challenges of interdisciplinary research. These findings were used to develop an 18-item BASICS checklist to support future interdisciplinary collaborations. The five domains of the checklist are: (i) Blueprint, (ii) Attitudes, (iii) Staffing, (iv) Interactions and (v) Core Science. Conclusion: Interdisciplinary work has the potential to advance public health science but the numerous challenges should not be underestimated. Use of a checklist, such as BASICS, when planning and managing projects may help future collaborations to avoid some of the common pitfalls of interdisciplinary research

The reduced kinome of Ostreococcus tauri:core eukaryotic signalling components in a tractable model species

BACKGROUND: The current knowledge of eukaryote signalling originates from phenotypically diverse organisms. There is a pressing need to identify conserved signalling components among eukaryotes, which will lead to the transfer of knowledge across kingdoms. Two useful properties of a eukaryote model for signalling are (1) reduced signalling complexity, and (2) conservation of signalling components. The alga Ostreococcus tauri is described as the smallest free-living eukaryote. With less than 8,000 genes, it represents a highly constrained genomic palette. RESULTS: Our survey revealed 133 protein kinases and 34 protein phosphatases (1.7% and 0.4% of the proteome). We conducted phosphoproteomic experiments and constructed domain structures and phylogenies for the catalytic protein-kinases. For each of the major kinases families we review the completeness and divergence of O. tauri representatives in comparison to the well-studied kinomes of the laboratory models Arabidopsis thaliana and Saccharomyces cerevisiae, and of Homo sapiens. Many kinase clades in O. tauri were reduced to a single member, in preference to the loss of family diversity, whereas TKL and ABC1 clades were expanded. We also identified kinases that have been lost in A. thaliana but retained in O. tauri. For three, contrasting eukaryotic pathways – TOR, MAPK, and the circadian clock – we established the subset of conserved components and demonstrate conserved sites of substrate phosphorylation and kinase motifs. CONCLUSIONS: We conclude that O. tauri satisfies our two central requirements. Several of its kinases are more closely related to H. sapiens orthologs than S. cerevisiae is to H. sapiens. The greatly reduced kinome of O. tauri is therefore a suitable model for signalling in free-living eukaryotes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-640) contains supplementary material, which is available to authorized users