Psychiatric manifestations of ATP13A2 mutations

Background: Biallelic mutations in ATP13A2 were identified as the cause of Kufor-Rakeb disease, a pallido-pyramidal syndrome characterized by young-onset dystonia-parkinsonism with vertical supranuclear gaze palsy, spasticity, and cognitive decline. The phenotypic spectrum has broadened since, but predominantly psychiatric or behavioral manifestations have not been highlighted. Cases: Here we report the clinical, radiological, and genetic findings in 2 unrelated patients with ATP13A2 mutations. One patient had a prominent behavioral (autistic spectrum) presentation and the other a psychiatric (paranoid psychosis) presentation. Both had additional features, such as delayed milestones, ataxia, pyramidal signs, upgaze restriction, or impaired cognition to varying extent, but these were partly subtle or developed later in the disease course. Conclusion: Prominent behavioral or psychiatric features can be the first or most prominent manifestation of ATP13A2-related disease. They may be a diagnostic clue in patients with ataxia, spasticity, or parkinsonism and may require an interdisciplinary neurological and psychiatric treatment approach

Rapid-onset dystonia-Parkinsonism phenotype consistency for a novel variant of ATP1A3 in patients across 3 global populations

info:eu-repo/semantics/publishedVersio

BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly

We show that BJcuL, a lectin purified from Bothrops jararacussu venom, exerts cytotoxic effects to gastric carcinoma cells MKN45 and AGS. This effect was due to the direct interaction with specific glycans on the cells surface and was observed by cell viability decrease, disorganization of actin filaments and apoptosis. In addition, BJcuL was able to reduce tumor cell adhesion to matrigel, what was inhibited by specific carbohydrate or partially inhibited when cells were pre-incubated with matrigel. Our results suggest that BJcuL was able to promote apoptosis in both tumor cells lines and therefore has a prospect for potential use in cancer therapy. (C) 2011 Elsevier Ltd. All rights reserved.CNP

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Evaluation of side-effects of glyphosate mediated control of giant reed (Arundo donax) on the structure and function of a nearby Mediterranean river ecosystem

The aim of this study was to evaluate the effect of the application of the herbicide Herbolex (Aragonesas Agro, S.A., Madrid, Spain) to control giant reed (Arundo donax), which has glyphosate as active ingredient, on the structure and function of a nearby river ecosystem. Specifically, we assessed glyphosate environmental fate in the surrounding water and its effects on transplanted Daphnia magna, field collected caddisfly (Hydropsyche exocellata) and on benthic macroinvertebrate structure assemblages. Investigations were conducted in the industrialized and urbanized Mediterranean river Llobregat (NE Spain) before and after a terrestrial spray of glyphosate. Four locations were selected to include an upstream site and three affected ones. Measured glyphosate levels in river water following herbicide application were quite high (20-60 mu g/l) with peak values of 137 mu g/l after three days. After 12 days of its application, leaching of glyphosate from sprayed riverbanks was quite high in pore water (20-85 mu g/l) but not in the river. Closely linked with the measured poor habitat and water physicochemical conditions, macroinvertebrate communities were dominated by taxa tolerant to pollution and herbicide application did not affect the abundance or number of taxa in any location. Nevertheless, significant specific toxic effects on transplanted D. magna and field collected H. exocellata were observed. Effects included D. magna feeding inhibition and oxidative stress related responses such as increased antioxidant enzyme activities related with the metabolism of glutathione and increased levels of lipid peroxidation. These results emphasize the importance of combined chemical, ecological and specific biological responses to identify ecological effects of pesticides in the field. (C) 2010 Elsevier Inc. All rights reserved

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes-CACNA1A , ITPR1 , SPTBN2 , and KCNC3-were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1- associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A , ITPR1 , and SPTBN2 , the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist