A class-wide phylogenetic assessment of Dothideomycetes

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Medication reconciliation by a pharmacy technician in a mental health assessment unit

Background Medication discrepancies are common when patients cross organisational boundaries. However, little is known about the frequency of discrepancies within mental health and the efficacy of interventions to reduce discrepancies. Objective To evaluate the impact of a pharmacy-led reconciliation service on medication discrepancies on admissions to a secondary care mental health trust. Setting In-patient mental health services. Methods Prospective evaluation of pharmacy technician led medication reconciliation for admissions to a UK Mental Health NHS Trust. From March to June 2012 information on any unintentional discrepancies (dose, frequency and name of medication); patient demographics; and type and cause of the discrepancy was collected. The potential for harm was assessed based on two scenarios; the discrepancy was continued into primary care, and the discrepancy was corrected during admission. Logistic regression identified factors associated with discrepancies. Main outcome measure Mean number of discrepancies per admission corrected by the pharmacy technician. Results Unintentional medication discrepancies occurred in 212 of 377 admissions (56.2 %). Discrepancies involving 569 medicines (mean 1.5 medicines per admission) were corrected. The most common discrepancy was omission (n = 464). Severity was assessed for 114 discrepancies. If the discrepancy was corrected within 16 days the potential harm was minor in 71 (62.3 %) cases and moderate in 43 (37.7 %) cases whereas if the discrepancy was not corrected the potential harm was minor in 27 (23.7 %) cases and moderate in 87 (76.3 %) cases. Discrepancies were associated with both age and number of medications; the stronger association was age. Conclusions Medication discrepancies are common within mental health services with potentially significant consequences for patients. Trained pharmacy technicians are able to reduce the frequency of discrepancies, improving safety