Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON collaborative study

Malaltia de Parkinson; Prevalència; Distribució per edatsEnfermedad de Parkinson; Prevalencia; Distribución de edadParkinson Disease; Prevalence; Age DistributionObjectives: To assess and compare the prevalence of parkinsonism and Parkinson's disease in five European populations that were surveyed with similar methodology and diagnostic criteria.Methods: Joint analysis of five community surveys--Gironde (France), eight centres in Italy, Rotterdam (The Netherlands), Girona (Spain), and Pamplona (Spain)--in which subjects were screened in person for parkinsonism. Overall, these surveys comprised 14,636 participants aged 65 years or older.Results: The overall prevalence (per 100 population), age adjusted to the 1991 European standard population, was 2.3 for parkinsonism and 1.6 for Parkinson's disease. The overall prevalence of parkinsonism for the age groups 65 to 69, 70 to 74, 75 to 79, 80 to 84, and 85 to 89 years was respectively, 0.9, 1.5, 3.7, 5.0, and 5.1. The corresponding age specific figures for Parkinson's disease were 0.6, 1.0, 2.7, 3.6, and 3.5. After adjusting for age and sex, the prevalence figures did not differ significantly across studies, except for the French study in which prevalence was lower. Prevalence was similar in men and women. Overall, 24% of the subjects with Parkinson's disease were newly detected through the surveys.Conclusions: Prevalence of both parkinsonism and Parkinson's disease increased with age, without significant differences between men and women. There was no convincing evidence for differences in prevalence across European countries. A substantial proportion of patients with Parkinson's disease went undetected in the general population

Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways

The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado–Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated athogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the nregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.This work was supported by grants from Fundacão Ciência eTecnologia (FCT) to P.M. (PTDC/SAU-GMG/64076/2006, PTDC/SAU-GMG/112617/2009, SFRH/BD/27258/2006 to A.T.C., UMINHO/BI/052/2010 to A.J. and SFRH/BD/51059/2010 to A.N.C.), from the National Ataxia Foundation to PM and from the National Institutes of Health (NIGMS, NIA and NINDS) to R.M. This work was also granted by the Hospital San Rafael (Coruna) with the Rafael Hervada prize on Biomedical Research (2010)

African Bush Viper Envenomation: A Case Report

Atheris squamigera envenomation is an infrequently documented occurrence in the United States (US). Cases of envenomation may induce severe coagulopathies, renal failure, and potentially life-threatening hemorrhage. Currently, there are no antivenoms specific to the Atheris genus, but there have been documented cases of the use of antivenoms for other species. A 26-year-old man presented to the emergency department (ED) complaining of swelling and discomfort in his left foot after being bitten by an Atheris squamigera that he kept as a pet.After performing a physical exam, it was noted that the patient’s envenomation was likely mild. Throughout his hospital stay, he developed lab abnormalities, most notably an elevated D-dimer and low fibrinogen. His clinical symptoms improved after a short stay, and he did not require antivenom treatment. This case highlights a rare, but potentially life-threatening envenomation that may be encountered in the US due to the continued practice of exotic pet ownership and sales. Moreover, procurement of antivenom for non-native species poses a unique challenge to US physicians responsible for treating these patients

A Proton Recoil Telescope for the characterisation of the neutron beam at n TOF

The neutron induced fission cross section of 235U is extensively used as a reference for neutron fluence measurements in various applications. At intermediate energies, the 235U(n,f) cross section plays an important role also for fundamental nuclear physics. Despite its widespread use, no data exist on neutroninduced fission of 235U above 200 MeV. Hence, there is a clear and long-standing demand from the International Atomic Energy Agency (IAEA) to complement the experimental database from 20 MeV to 1 GeV. For this purpose at the neutron facility n TOF at CERN the measurement of 235U(n,f) cross section was planned in October 2018, taking advantage of the intense neutron beam with a wide energy spectrum available in the experimental area. The cross section measurement will be performed relative to the elastic neutron-proton scattering, a very well known reaction generally accepted as primary reference. A prototype of the Proton Recoil Telescope detector, that will be used to measure the incident neutron flux, has been built and tested at n TOF in 2017

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Highly predictive genetic markers distinguish drug-type from fiber-type cannabis sativa L

Genetic markers can be used in seeds and in plants to distinguish drug-type from fiber-type Cannabis Sativa L. varieties even at early stages, including pre-germination when cannabinoids are not accumulated yet. With this aim, this paper reports sequencing results for tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) genes from 21 C. sativa L. varieties. Taking into account that THCAS- and CBDAS-derived enzymes compete for the same substrate, the novelty of this work relies in the identification of markers based on bothTHCASandCBDASrather than THCAS alone. Notably, in our panel, we achieved an adequate degree of discrimination (AUC 100%) between drug-type and fiber-type cannabis samples. Our sequencing approach allowed identifying multiple genetic markers (single-nucleotide polymorphisms\u2014SNPs\u2014and a deletion/insertion) that effectively discriminate between the two subgroups of cannabis, namely fiber type vs. drug type. We identified four functional SNPs that are likely to induce decreased THCAS activity in the fiber-type cannabis plants. We also report the finding on a deletion in the CBDAS gene sequence that produces a truncated protein, possibly resulting in loss of function of the enzyme in the drug-type varieties. Chemical analyses for the actual concentration of cannabinoids confirmed the identification of drug-type rather than fiber-type genotypes. Genetic markers permit an early identification process for forensic applications while simplifying the procedures related to detection of therapeutic or industrial hemp