Multifocal Transcranial Direct Current Stimulation in Primary Progressive Aphasia Does Not Provide a Clinical Benefit Over Speech Therapy

Primary progressive aphasia (PPA) is a group of neurodegenerative disorders including Alzheimer's disease and frontotemporal dementia characterized by language deterioration. Transcranial direct current stimulation (tDCS) is a non-invasive intervention for brain dysfunction.To evaluate the tolerability and efficacy of tDCS combined with speech therapy in the three variants of PPA. We evaluate changes in fMRI activity in a subset of patients.Double-blinded, randomized, cross-over, and sham-controlled tDCS study. 15 patients with PPA were included. Each patient underwent two interventions: a) speech therapy + active tDCS and b) speech therapy + sham tDCS stimulation. A multifocal strategy with anodes placed in the left frontal and parietal regions was used to stimulate the entire language network. Efficacy was evaluated by comparing the results of two independent sets of neuropsychological assessments administered at baseline, immediately after the intervention, and at 1 month and 3 months after the intervention. In a subsample, fMRI scanning was performed before and after each intervention.The interventions were well tolerated. Participants in both arms showed clinical improvement, but no differences were found between active and sham tDCS interventions in any of the evaluations. There were trends toward better outcomes in the active tDCS group for semantic association and reading skills. fMRI identified an activity increase in the right frontal medial cortex and the bilateral paracingulate gyrus after the active tDCS intervention.We did not find differences between active and sham tDCS stimulation in clinical scores of language function in PPA patients

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome

Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. Results: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. Discussion: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS

Bacterivory by phototrophic picoplankton and nanoplankton in Arctic waters

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in FEMS Microbiology Ecology 82 (2012): 242–253, doi:10.1111/j.1574-6941.2011.01253.x.Mixotrophy, the combination of phototrophy and heterotrophy within the same individual, is widespread in oceanic systems. Yet, neither the presence nor ecological impact of mixotrophs has been identified in an Arctic marine environment. We quantified nano- and picoplankton during early autumn in the Beaufort Sea and Canada Basin and determined relative rates of bacterivory by heterotrophs and mixotrophs. Results confirmed previous reports of low microbial biomass for Arctic communities in autumn. The impact of bacterivory was relatively low, ranging from 0.6 x 103 to 42.8 x 103 bacteria mL-1 day-1, but it was often dominated by pico- or nano-mixotrophs. From 1-7% of the photosynthetic picoeukaryotes were bacterivorous, while mixotrophic nanoplankton abundance comprised 1-22% of the heterotrophic and 2-32% of the phototrophic nanoplankton abundance, respectively. The estimated daily grazing impact was usually < 5% of the bacterial standing stock, but impacts as high as 25% occurred. Analysis of denaturing gradient gel electrophoresis band patterns indicated that communities from different depths at the same site were appreciably different, and that there was a shift in community diversity at the midpoint of the cruise. Sequence information from DGGE bands reflected microbes related to ones from other Arctic studies, particularly from the Beaufort Sea.Funding for participation in the 2008 cruise was provided by the Woods Hole Oceanographic Institution Arctic Research Initiative, with additional support from National Science Foundation Grants OPP-0838847 (RWS) and OPP-0838955 (RJG)

Major Role of Microbes in Carbon Fluxes during Austral Winter in the Southern Drake Passage

Carbon cycling in Southern Ocean is a major issue in climate change, hence the need to understand the role of biota in the regulation of carbon fixation and cycling. Southern Ocean is a heterogeneous system, characterized by a strong seasonality, due to long dark winter. Yet, currently little is known about biogeochemical dynamics during this season, particularly in the deeper part of the ocean. We studied bacterial communities and processes in summer and winter cruises in the southern Drake Passage. Here we show that in winter, when the primary production is greatly reduced, Bacteria and Archaea become the major producers of biogenic particles, at the expense of dissolved organic carbon drawdown. Heterotrophic production and chemoautotrophic CO2 fixation rates were substantial, also in deep water, and bacterial populations were controlled by protists and viruses. A dynamic food web is also consistent with the observed temporal and spatial variations in archaeal and bacterial communities that might exploit various niches. Thus, Southern Ocean microbial loop may substantially maintain a wintertime food web and system respiration at the expense of summer produced DOC as well as regenerate nutrients and iron. Our findings have important implications for Southern Ocean ecosystem functioning and carbon cycle and its manipulation by iron enrichment to achieve net sequestration of atmospheric CO2

Evaluation of the national surveillance system for point-prevalence of healthcare-associated infections in hospitals and in long-term care facilities for elderly in Norway, 2002-2008

<p>Abstract</p> <p>Background</p> <p>Since 2002, the Norwegian Institute of Public Health has invited all hospitals and long-term care facilities for elderly (LTCFs) to participate in two annual point-prevalence surveys covering the most frequent types of healthcare-associated infections (HAIs). In a comprehensive evaluation we assessed how well the system operates to meet its objectives.</p> <p>Methods</p> <p>Surveillance protocols and the national database were reviewed. Data managers at national level, infection control practitioners and ward personnel in hospitals as well as contact persons in LTCFs involved in prevalence data collection were surveyed.</p> <p>Results</p> <p>The evaluation showed that the system was structurally simple, flexible and accepted by the key partners. On average 87% of hospitals and 32% of LTCFs participated in 2004-2008; high level of data completeness was achieved. The data collected described trends in the prevalence of reportable HAIs in Norway and informed policy makers. Local results were used in hospitals to implement targeted infection control measures and to argue for more resources to a greater extent than in LTCFs. Both the use of simplified Centers for Disease Control and Prevention (CDC) definitions and validity of data seemed problematic as compliance with the standard methodology were reportedly low.</p> <p>Conclusions</p> <p>The surveillance system provides important information on selected HAIs in Norway. The system is overall functional and well-established in hospitals, however, requires active promotion in LTCFs. Validity of data needs to be controlled in the participating institutions before reporting to the national level.</p

Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educators

We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms

Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed