Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study

Background Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). Objective To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. Design Open-label trial evaluating twice-daily DM/Q over 90 days. Study participants Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. Methods PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. Setting 150 U.S. centers. Main Outcome Measurements Primary endpoint was change in Center for Neurologic Study–Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life–Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). Results DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, –5.6 [5.2]; day 90, –8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had “much improved” or “very much improved” on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (–3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (–3.2 [5.3], P<.001) and 90 (–5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). Conclusions DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials

Optical and mechanical design of the extreme AO coronagraphic instrument MagAO-X

Here we review the current optical mechanical design of MagAO-X. The project is post-PDR and has finished the design phase. The design presented here is the baseline to which all the optics and mechanics have been fabricated. The optical/mechanical performance of this novel extreme AO design will be presented here for the first time. Some highlights of the design are: 1) a floating, but height stabilized, optical table; 2) a Woofer tweeter (2040 actuator BMC MEMS DM) design where the Woofer can be the current f/16 MagAO ASM or, more likely, fed by the facility f/11 static secondary to an ALPAO DM97 woofer; 3) 22 very compact optical mounts that have a novel locking clamp for additional thermal and vibrational stability; 4) A series of four pairs of super-polished off-axis parabolic (OAP) mirrors with a relatively wide FOV by matched OAP clocking; 5) an advanced very broadband (0.5-1.7micron) ADC design; 6) A Pyramid (PWFS), and post-coronagraphic LOWFS NCP wavefront sensor; 7) a vAPP coronagraph for starlight suppression. Currently all the OAPs have just been delivered, and all the rest of the optics are in the lab. Most of the major mechanical parts are in the lab or instrument, and alignment of the optics has occurred for some of the optics (like the PWFS) and most of the mounts. First light should be in 2019A.Comment: 10 pages, proc. SPIE 10703, Adaptive Optics IV, Austin TX, June 201

Heavy metal content of vegetables irrigated with mixtures of wastewater and sewage sludge in Zimbabwe: Implications for human health

There is growing public concern in Zimbabwe over the illegal cultivation of vegetables on soils amended with sewage sludge or irrigated with admixtures of sewage and sewage sludge. Excessive accumulation of heavy metals in agricultural soils may not only result in environmental contamination, but lead to elevated heavy metal uptake by crops, which may affect food quality and safety. The work reported here studied heavy metal concentrations in crops irrigated with sewage sludge and sewage/sewage sludge admixtures at Firle Municipal Farm in Harare. The crops analysed in this study are heavily contaminated with the four regulated elements Cd, Cu, Pb and Zn. This contamination is at its highest in two of the staple dietary crops maize and tsunga. Tsunga leaves contained 3.68 mg kg-1 Cd, over 18 times the permissible level by the EU standards (0.2 mg kg-1); Cu concentrations were 111 mg kg-1, 5 times the EU Standard (20 mg kg-1); concentrations of Pb were 6.77 mg kg-1, over 22 times the permissible levels allowed by both EU standards and UK guidelines (0.3 mg kg-1); Zn concentrations were 221 mg kg-1, over 4 times the guideline value (50 mg kg-1). The other plants (beans, maize, peppers and sugarcane) also contained concentrations of heavy metals above the permissible levels. Furthermore the concentrations observed in this study were higher than those reported by other workers who have examined vegetation from other contaminated sites. This study highlights the potential risks involved in the cultivation and consumption of vegetables on plots irrigated with sewage sludge, a practice which may place at risk the health of the urban population who consume these vegetables

Reshaping our understanding of species’ roles in landscape-scale networks

Data associate with Ecology Letters manuscript number: ELE-01021-2018.R2; Hackett et al. Reshaping our understanding of species’ roles in landscape-scale networks<div><br></div><div>See READ ME text file for specific detail</div

Loss of AP-2delta reduces retinal ganglion cell numbers and axonal projections to the superior colliculus

Background: AP-2 delta is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2 delta is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain. Results: AP-2 delta knockout results in loss of Brn3c (Pou4f3) expression in AP-2 delta -positive RGCs. While AP-2 delta-/- mice have morphologically normal retinas at birth, there is a significant reduction in retinal ganglion cell numbers by P21, after eye opening. Chromatin immunoprecipitation indicates that Brn3c is a target of AP-2 delta in the retina. Using fluorochrome-conjugated cholera toxin subunit B to trace ganglion cell axons from the eye to the major visual pathways in the brain, we found 87 % and 32 % decreases in ipsilateral and contralateral projections, respectively, to the superior colliculus in AP-2 delta-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised. Conclusions: AP-2 delta is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2 delta alters retinal axonal projections to visual centers of the brain, with ipsilaterial projections to the superior colliculus being the most dramatically affected. Our results have important implications for integration of the visual signal at the superior colliculus

Efficiency of the traditional practice of traps to stimulate black truffle production, and its ecological mechanisms

The black truffle Tuber melanosporum was disseminated all over the world, propelled by the development of a wide variety of empirical practices. A widespread practice, called ‘truffle trap’, consists of placing pieces of truffles into excavations dug under host trees, and of collecting truffle in these traps in the next years. This research aims at (1) evaluating the effect of this practice on fruitbody production based on the analysis of 9924 truffle traps installed in 11 orchards across T. melanosporum native area in France and (2) exploring the mechanisms involved in fruitbody emergence using traps where the genotypes of introduced truffles were compared with those of fruitbodies collected in the same traps. We confirmed that truffle traps provide a major and highly variable part of truffle ground production, representing up to 89% of the collected fruitbodies. We evidenced a genetic link between introduced spores and collected fruitbodies, and then demonstrated that truffle growers provide paternal partners for mating with local maternal mycelia. We also highlighted that soil disturbance stimulate the vegetative development of established maternal mycelia. This research supports that a widely used traditional practice enhances fruitbody production by shaping favorable conditions and providing sexual partners required for fruiting.info:eu-repo/semantics/publishedVersio

The genus <i>Elaphomyces </i>(<i>Ascomycota</i>, <i>Eurotiales</i>):a ribosomal DNA-based phylogeny and revised systematics of European 'deer truffles'

Elaphomyces (‘deer truffles’) is one of the most important ectomycorrhizal fungal genera in temperate and subarctic forest ecosystems, but also one of the least documented in public databases. The current systematics are mainly based on macromorphology, and is not significantly different from that proposed by Vittadini (1831). Within the 49 species recognised worldwide, 23 were originally described from Europe and 17 of these were described before the 20th century. Moreover, very recent phylogenetic treatments of the genus are mainly based on a few extra-European species and most common European species are still poorly documented. Based on an extensive taxonomic sampling mainly made in the biogeographically rich Cantabrian area (Spain), complemented with collections from France, Greece, Italy, Norway, Portugal and Sweden, all currently recognized species in Europe have been sequenced at the ITS and 28S of the rDNA. Combined phylogenetic analyses yielded molecular support to sections Elaphomyces and Ceratogaster (here emended), while a third, basal lineage encompasses the sections Malacodermei and Ascoscleroderma as well as the tropical genus Pseudotulostoma. Species limits are discussed and some taxa formerly proposed as genuine species based on morphology and biogeography are re-evaluated as varieties or forms. Spore size and ornamentation, features of the peridial surface, structure of the peridium, and the presence of mycelium patches attached to the peridial surface emerge as the most significant systematic characters. Four new species: E. barrioi, E. quercicola, E. roseolus and E. violaceoniger, one new variety: E. papillatus var. sulphureopallidus, and two new forms: E. granulatus forma pallidosporus and E. anthracinus forma talosporus are introduced, as well as four new combinations in the genus: E. muricatus var. reticulatus, E. muricatus var. variegatus, E. papillatus var. striatosporus and E. morettii var. cantabricus. Lectotypes and epitypes are designated for most recognised species. For systematic purposes, new infrageneric taxa are introduced: E. sect. Ascoscleroderma stat. nov., E. subsect. Sclerodermei stat. nov., E. subsect. Maculati subsect. nov., E. subsect. Muricati subsect. nov., and E. subsect. Papillati subsect. nov. Lastly, E. laevigatus, E. sapidus, E. sulphureopallidus and E. trappei are excluded from the genus and referred to Rhizopogon roseolus, Astraeus sapidus comb. nov., Astraeus hygrometricus and Terfezia trappei comb. nov. (syn.: Terfezia cistophila), respectively

A national survey of antimicrobial stewardship content in Canadian entry-to-practice pharmacy programs

Abstract Objective: To describe the current landscape of antimicrobial stewardship (AMS) instruction in Canadian entry-to-practice pharmacy programs and the perceived barriers and facilitators to optimizing teaching and learning. Design: Electronic survey. Participants: Faculty representatives from the 10 Canadian entry-to-practice pharmacy programs, including content experts and faculty leadership. Methods: A review of international literature pertaining to AMS in pharmacy curricula informed a 24-item survey, which was open for completion from March to May of 2021. Curriculum content questions were developed using AMS topics recommended by pharmacy educators in the United States, and professional roles described by the Association of Faculties of Pharmacy of Canada. Results: All 10 Canadian faculties returned a completed survey. All programs reported teaching AMS principles in their core curricula. Content coverage varied, with programs teaching, on average, 68% of the recommended AMS topics from the United States. Potential gaps were identified within the professional roles of “communicator” and “collaborator.” Didactic methods of content delivery and student assessment, such as lectures and multiple-choice questions, were most frequently used. Three programs offered additional AMS content in their elective curricula. Experiential rotations in AMS were commonly offered, though teaching AMS in formalized interprofessional settings was rare. Curricular time constraints were identified by all programs as a barrier to enhancing AMS instruction. A course to teach AMS, a curriculum framework, and prioritization by the faculty’s curriculum committee were perceived as facilitators. Conclusions: Our findings highlight potential gaps and areas of opportunity within Canadian pharmacy AMS instruction