The nature of positive post-diagnostic support as experienced by people with young onset dementia.

Objectives: Studies on service needs of people with young onset dementia have taken a problem-oriented approach with resulting recommendations focusing on reducing service shortcomings. This study aimed to build on ‘what works’ in real-life practice by exploring the nature of post-diagnostic support services that were perceived positively by younger people with dementia and carers. Method: Positive examples of support were gathered between August 2017 and September 2018, via a national survey. Inductive thematic analysis was employed to explore the nature of positively experienced services provided for younger people with dementia, including analysis of what was provided by positively experienced services. Results: Two hundred and thirty-three respondents reported 856 positive experiences of support. Data analysis yielded eight themes regarding the objectives of positive services: Specialist Advice and Information on Young Onset Dementia, Access to Age-appropriate Services, Interventions for Physical and Mental Health, Opportunities for Social Participation, Opportunities to Have a Voice, Enablement of Independence while Managing Risk, Enablement of Financial Stability, and Support Interventions for Family Relationships. Conclusion: The study findings (a) suggest that positive services may collectively create an enabling-protective circle that supports YPD to re-establish and maintain a positive identity in the face of young onset dementia, and (b) provide a basis from which future good practice can be developed

Services for people with young onset dementia: The ‘Angela’ project national UK survey of service use and satisfaction

Objectives Young onset dementia is associated with distinctive support needs but existing research on service provision has been largely small scale and qualitative. Our objective was to explore service use, cost and satisfaction across the UK. Methods Information about socio‐demographic characteristics, service use and satisfaction were gathered from people with young onset dementia and/or a family member/supporter via a national survey. Results Two hundred and thirty‐three responses were analysed. Diagnosis was most commonly received through a Memory Clinic or Neurology. The type of service delivering diagnosis impacted on post‐diagnostic care. Those diagnosed in specialist young onset dementia services were more likely to receive support within the first six weeks and receive ongoing care in the service where they were diagnosed. Ongoing care management arrangements varied but generally care was lacking. Around 42% reported no follow‐up during 6‐weeks after diagnosis; over a third reported seeing no health professional within the previous three months; just over a third had a key worker and just under a third had a care plan. Satisfaction and quality of care were highest in specialist services. Almost 60% of family members spent over 5 hours per day caring; Median costs of health and social care, 3 months, 2018, were £394 (IQR £389 to 640). Conclusions Variation across diagnostic and post‐diagnostic care pathways for young onset dementia leads to disparate experiences, with specialist young onset services being associated with better continuity, quality and satisfaction. More specialist services are needed so all with young onset dementia can access age‐appropriate care

Dravet syndrome patient‐derived neurons suggest a novel epilepsy mechanism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99647/1/ana23897.pd

Early-branching gut fungi possess a large, comprehensive array of biomass-degrading enzymes

available in PMC 2016 November 07The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. We developed a systems-level approach that integrates transcriptomic sequencing, proteomics, phenotype, and biochemical studies of relatively unexplored basal fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, untreated plant biomass and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite-repressed and are further regulated by a rich landscape of noncoding regulatory RNAs. Additionally, we identified several promising sequence-divergent enzyme candidates for lignocellulosic bioprocessing.United States. Dept. of Energy. Office of Science (Biological and Environmental Research (BER) program)United States. Department of Energy (DOE Grant DE-SC0010352)United States. Department of Agriculture (Award 2011-67017-20459)Institute for Collaborative Biotechnologies (grant W911NF-09-0001

Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The role of sodium channel alpha and beta subunits in myelinating glia and demyelinating disorders.

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS) in which patients experience a variety of neurological symptoms resulting from demyelination, axonal degeneration and axonal loss leading to conduction block or aberrant conduction. Voltage-gated sodium channels (VGSCs) have been implicated in the pathogenesis of MS and its animal model, Experimental Allergic Encephalomyelitis (EAE). We previously generated a Scn2b (VGSC β2) null mouse which exhibits a 40-50% decrease in neuronal VGSC cell surface expression. We hypothesized that Scn2b deletion would result in neuroprotection in EAE due to a decrease in excitotoxicity. The goal of this thesis was to determine the role of VGSCs in CNS demyelinating disease and myelinating glia using three different systems: Scn2b null mice, human MS brain, and cultured rat oligodendrocytes. Scn2b deletion led to improved clinical outcome in the EAE model, with mice displaying less severe clinical symptoms, decreases in lethality, and reductions in axonal loss, degeneration and demyelination. In EAE, these mice also displayed alterations in subcellular localization and protein expression levels of the VGSC α subunit Nav1.1, a channel which has not been studied previously in demyelinating disease. We then translated these experiments to the study of post-mortem human brain. MS brain displayed increased Nav1.1 protein levels in white and grey matter and changes in expression of β subunits in glia as compared to control brain. Finally, we examined the expression of VGSC α and β subunits in cultured rat oligodendrocytes at two stages of differentiation. These cells displayed differential expression of α and β subunits, with VGSC α, β1 and β3 subunits expressed at both stages while β2 and β4 were expressed at low levels. To summarize, the results presented in this thesis implicate VGSC β2 and Nav1.1 subunits in the pathogenesis of CNS demyelinating disease in both human and mouse, and suggest roles for VGSC α and β subunits in myelinating glial cell precursors. VGSC β2 and Nav1.1 subunits may also offer novel targets for the development of therapeutics for the treatment of MS.Ph.D.Cellular & Molecular BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64629/1/homalley_1.pd

Screening for depression after stroke : developing protocols for the occupational therapist

Depression after stroke is common and can have a substantial effect on rehabilitation outcome. Despite this, the routine screening that has been recommended is only taking place around half the time. Occupational therapists have training that well positions them to provide screening. In a local stroke unit, the psychology and occupational therapy departments worked together, considering relevant research, clinical considerations (such as identifying suicidal ideas) and practical issues (such as ease of administration and patient compliance) to determine screening protocols that could be enacted by occupational therapists. Two protocols were developed, one for people under 65 years of age and one for people aged 65 years or older

Scn1b deletion leads to increased tetrodotoxin‐sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts

Na+ current (INa) is determined not only by the properties of the pore‐forming voltage‐gated Na+ channel (VGSC) α subunit, but also by the integrated function of a molecular aggregate (the VGSC complex) that includes the VGSC β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including cases of Brugada syndrome and sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null mouse models to understand better the relation between Scn1b expression, and cardiac electrical function. Using a combination of macropatch and scanning ion conductance microscopy we show that loss of Scn1b in juvenile null animals resulted in increased tetrodotoxin‐sensitive INa but only in the cell midsection, even before full T‐tubule formation; the latter occurred concurrent with increased message abundance for the neuronal Scn3a mRNA, suggesting increased abundance of tetrodotoxin‐sensitive NaV1.3 protein and yet its exclusion from the region of the intercalated disc. Ventricular myocytes from cardiac‐specific adult Scn1b null animals showed increased Scn3a message, prolonged action potential repolarization, presence of delayed after‐depolarizations and triggered beats, delayed Ca2+ transients and frequent spontaneous Ca2+ release events and at the whole heart level, increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca2+ homeostasis were prevented by 100 nm tetrodotoxin. Our results suggest that life‐threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na+ channel α subunit, can be partly consequent to disrupted intracellular Ca2+ homeostasis in ventricular myocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110823/1/tjp6322.pd

The ANGELA Project: improving diagnosis and post-diagnostic support for younger people with dementia and their families/supporters

Objectives: Younger people with dementia face significant challenges in gaining access to age- and needs-appropriate support. In this paper, we tell the story so far, of the ANGELA Research Project, which seeks to develop guidance to improve the ‘dementia journey’ for younger people with dementia and their families/supporters. Design: Our story is one of a research group aiming to conduct clinically relevant research to achieve positive changes for younger people with dementia. Our research journey will last 3 years and is now almost one year in. In this article, we aim to convey some of the decisions we have made to date, and what lies ahead for a successful implementation. Methods: So far, we have been forming as a research group and turning our initial ideas into plans that will work in the real world. Our methods for ensuring all elements of the project work well have involved internal and external aspects and processes. These have included involvement with and feedback from experts-by-experience and an advisory panel. Results: To date we have generated a protocol for all the key elements and have launched the Improving Support and Service Use Survey; a national survey gathering evidence from younger people with dementia and their supporters. In this article, we present how we aim to move forward to bring positive real-life changes to the lives of those affected by young onset dementia. Conclusions: There is a cautiously happy ending to this first phase, as we are now collecting data. However, the judgement of whether the Angela Project is a success overall will depend on whether it makes a difference at its conclusion to younger people with dementia and their supporters