Pharmacist educators in family medicine residency programs: A qualitative analysis

BACKGROUND: 25-29% of North American family medicine residency programs utilize a pharmacist to teach residents. Little is known about the impact that these pharmacist educators have on residency training. The purpose of this study was to examine the experiences of residents, residency directors and pharmacists within Canadian family medicine residency programs that employ a pharmacist educator to better understand the impact of the role. METHODS: Recruitment from three cohorts (residents, residency directors, pharmacists) within family medicine residency programs across Canada for one-on-one semi-structured interviews followed by thematic analysis of anonymized transcript data. RESULTS: 11 residents, 6 residency directors and 17 pharmacist educators participated in interviews. Data themes were: (1) strong value of the teaching with respect to improved resident knowledge, confidence and patient care delivery; (2) lack of a formal pharmacotherapy curriculum; (3) desire for expansion of pharmacist teaching; (4) impact of teaching on collaboration; (5) impact of teaching on residency program faculty; and (6) lack of criticism of the role. CONCLUSIONS: The pharmacist educator role is valued within residency programs across Canada and the role has a positive impact on several important aspects of family medicine resident training. Suggestions for improvement focused on expanding the teaching role and on implementing a formal curriculum for pharmacist educators to follow

Investigating the efficacy and mechanism of action of mesenchymal stromal cell therapy in burn wound healing

Several studies suggest that mesenchymal stromal cell (MSC) therapy may be efficacious in accelerating wound healing. Which source of MSC is therapeutically superior has not been well established, especially in large clinically relevant animal models. We therefore investigated the efficacy of Bone marrow-MSC (BM-MSC) and Adipose-MSC (AD-MSC) in the treatment of burn wounds in a large porcine model. Donor matched allogeneic AD-MSC and BM-MSC were applied onto partial thickness burns within a fibrin hydrogel. MSC therapy was similarly efficacious in both groups, increasing wound closure, angiogenesis and collagen content, associated with increased wound maturity at two weeks. To augment this therapeutic response, priming of MSC with inflammatory cytokines was explored. Administration of MSC primed with TNFα resulted in a significant acceleration of burn wound closure, re-epithelialisation and increased angiogenesis, AD-MSC and BM-MSC were therapeutically equivalent in their response to TNFα. We hypothesised that MSC derived CCL-2 may be involved in the MSC therapeutic effect by facilitating macrophage repolarisation and may also play a role in TNFα pre-treatment as CCL2 is greatly induced by TNFα. To further delineate this mechanism, MSC isolated from CCL-2 deficient mice (CCL-2 KO) were applied to excisional wounds in wild-type (WT) mice. Interestingly, CCL-2 deficiency in MSC completely abrogated the therapeutic response compared to WT MSC. CCL-2 KO MSC were unable to repolarise macrophages to the same extent as WT and this was accompanied by a reduced angiogenesis and re-epithelialisation of the wounds at day 10. TNFα pre-treatment of WT MSC significantly increased therapeutic efficacy, resulting in complete re-epithelisation of all wounds by day 10. CCL-2 KO MSC responded somewhat, with increased CD206+ macrophages and reduced Ly6G+ neutrophils present within the wound, but this biology had no effect on re-epithelialisation

Interfacing Relational Frame Theory with Cognitive Neuroscience: Semantic Priming, The Implicit Association Test, and Event Related Potentials

The current article argues that an important component of the research agenda for Relational Frame Theory will involve studying the functional relations that obtain between environmental events and the physiological activity that takes place inside the brain and central nervous system, with a particular focus on human language and cognition. In support of this view, five separate experiments are outlined. The first three experiments replicate and extend previous research reported by Hayes and Bisset (1998). Specifically, the research, using both reaction time and neurophysiological measures, supports the argument that there is a clear functional overlap between semantic and derived stimulus relations. Specifically, an evoked potential waveform typically associated with semantic processing (N400) is shown to be sensitive to equivalence versus non-equivalence relations. Experiments 4 and 5 indicate that these reaction time and evoked potential effects are not restricted to traditional lexical decision tasks, but can also be observed using the implicit association test. Furthermore, preliminary evidence suggests that evoked potentials might constitute a more sensitive measure of derived stimulus relations than response time. The results obtained across all five experiments support the view that the study of derived stimulus relations, combined with some of the procedures and measures of cognitive psychology and cognitive neuroscience, may provide an important inroad into the experimental analysis of semantic relations in human language

Protection induced by simultaneous subcutaneous and endobronchial vaccination with BCG/BCG and BCG/adenovirus expressing antigen 85A against Mycobacterium bovis in cattle

The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission

Water-soluble saponins accumulate in drought-stressed switchgrass and may inhibit yeast growth during bioethanol production

Background: Developing economically viable pathways to produce renewable energy has become an important research theme in recent years. Lignocellulosic biomass is a promising feedstock that can be converted into second-generation biofuels and bioproducts. Global warming has adversely affected climate change causing many environmental changes that have impacted earth surface temperature and rainfall patterns. Recent research has shown that environmental growth conditions altered the composition of drought-stressed switchgrass and directly influenced the extent of biomass conversion to fuels by completely inhibiting yeast growth during fermentation. Our goal in this project was to find a way to overcome the microbial inhibition and characterize specific compounds that led to this inhibition. Additionally, we also determined if these microbial inhibitors were plant-generated compounds, by-products of the pretreatment process, or a combination of both. Results: Switchgrass harvested in drought (2012) and non-drought (2010) years were pretreated using Ammonia Fiber Expansion (AFEX). Untreated and AFEX processed samples were then extracted using solvents (i.e., water, ethanol, and ethyl acetate) to selectively remove potential inhibitory compounds and determine whether pretreatment affects the inhibition. High solids loading enzymatic hydrolysis was performed on all samples, followed by fermentation using engineered Saccharomyces cerevisiae. Fermentation rate, cell growth, sugar consumption, and ethanol production were used to evaluate fermentation performance. We found that water extraction of drought-year switchgrass before AFEX pretreatment reduced the inhibition of yeast fermentation. The extracts were analyzed using liquid chromatography–mass spectrometry (LC–MS) to detect compounds enriched in the extracted fractions. Saponins, a class of plant-generated triterpene or steroidal glycosides, were found to be significantly more abundant in the water extracts from drought-year (inhibitory) switchgrass. The inhibitory nature of the saponins in switchgrass hydrolysate was validated by spiking commercially available saponin standard (protodioscin) in non-inhibitory switchgrass hydrolysate harvested in normal year. Conclusions: Adding a water extraction step prior to AFEX-pretreatment of drought-stressed switchgrass effectively overcame inhibition of yeast growth during bioethanol production. Saponins appear to be generated by the plant as a response to drought as they were significantly more abundant in the drought-stressed switchgrass water extracts and may contribute toward yeast inhibition in drought-stressed switchgrass hydrolysates

BSL2-compliant lethal mouse model of SARS-CoV-2 and variants of concern to evaluate therapeutics targeting the Spike protein

Since first reported in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly acquiring mutations, particularly in the spike protein, that can modulate pathogenicity, transmission and antibody evasion leading to successive waves of COVID19 infections despite an unprecedented mass vaccination necessitating continuous adaptation of therapeutics. Small animal models can facilitate understanding host-pathogen interactions, target selection for therapeutic drugs, and vaccine development, but availability and cost of studies in BSL3 facilities hinder progress. To generate a BSL2-compatibl

High temperatures and low soil moisture synergistically reduce switchgrass yields from marginal field sites and inhibit fermentation

‘Marginal lands’ are low productivity sites abandoned from agriculture for reasons such as low or high soil water content, challenging topography, or nutrient deficiency. To avoid competition with crop production, cellulosic bioenergy crops have been proposed for cultivation on marginal lands, however on these sites they may be more strongly affected by environmental stresses such as low soil water content. In this study we used rainout shelters to induce low soil moisture on marginal lands and determine the effect of soil water stress on switchgrass growth and the subsequent production of bioethanol. Five marginal land sites that span a latitudinal gradient in Michigan and Wisconsin were planted to switchgrass in 2013 and during the 2018–2021 growing seasons were exposed to reduced precipitation under rainout shelters in comparison to ambient precipitation. The effect of reduced precipitation was related to the environmental conditions at each site and biofuel production metrics (switchgrass biomass yields and composition and ethanol production). During the first year (2018), the rainout shelters were designed with 60% rain exclusion, which did not affect biomass yields compared to ambient conditions at any of the field sites, but decreased switchgrass fermentability at the Wisconsin Central–Hancock site. In subsequent years, the shelters were redesigned to fully exclude rainfall, which led to reduced biomass yields and inhibited fermentation for three sites. When switchgrass was grown in soils with large reductions in moisture and increases in temperature, the potential for biofuel production was significantly reduced, exposing some of the challenges associated with producing biofuels from lignocellulosic biomass grown under drought conditions

Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)

The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture facility with a 1.5 square degree field of view that will be fully dedicated to multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope on Maunakea, MSE will use 4332 fibers operating at three different resolving powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with dynamical fiber positioning that allows fibers to match the exposure times of individual objects. MSE will enable spectroscopic surveys with unprecedented scale and sensitivity by collecting millions of spectra per year down to limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100 m/s in high-resolution mode. This white paper describes science cases for stellar astrophysics and exoplanet science using MSE, including the discovery and atmospheric characterization of exoplanets and substellar objects, stellar physics with star clusters, asteroseismology of solar-like oscillators and opacity-driven pulsators, studies of stellar rotation, activity, and multiplicity, as well as the chemical characterization of AGB and extremely metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science Case of the Maunakea Spectroscopic Explore

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization.

ABSTRACT 5-Hydroxytryptamine (5-HT) 2C receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT 2C full agonist. Lorcaserin bound to human and rat 5-HT 2C receptors with high affinity (K i ϭ 15 Ϯ 1 nM, 29 Ϯ 7 nM, respectively), and it was a full agonist for the human 5-HT 2C receptor in a functional inositol phosphate accumulation assay, with 18-and 104-fold selectivity over 5-HT 2A and 5-HT 2B receptors, respectively. Lorcaserin was also highly selective for human 5-HT 2C over other human 5-HT receptors (5-HT 1A , 5-HT 3 , 5-HT 4C , 5-HT5 5A , 5-HT 6 , and 5-HT 7 ), in addition to a panel of 67 other G protein-coupled receptors and ion channels. Lorcaserin did not compete for binding of ligands to serotonin, dopamine, and norepinephrine transporters, and it did not alter their function in vitro. Behavioral observations indicated that unlike the 5-HT 2A agonist (Ϯ)-1-(2,5-dimethoxy-4-phenyl)-2-aminopropane, lorcaserin did not induce behavioral changes indicative of functional 5-HT 2A agonist activity. Acutely, lorcaserin reduced food intake in rats, an effect that was reversed by pretreatment with the 5-HT 2C -selective antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl-carbamoyl]indoline (SB242,084) but not the 5-HT 2A antagonist (R)-(ϩ)-␣-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907), demonstrating mediation by the 5-HT 2C receptor. Chronic daily treatment with lorcaserin to rats maintained on a high fat diet produced dose-dependent reductions in food intake and body weight gain that were maintained during the 4-week study. Upon discontinuation, body weight returned to control levels. These data demonstrate lorcaserin to be a potent, selective, and efficacious agonist of the 5-HT 2C receptor, with potential for the treatment of obesity. Serotonin mediates its physiological effects through at least 14 different receptors. The serotonin 5-HT 2 receptor subfamily contains three distinct receptor subtypes, 5-HT 2A , 5-HT 2B , and 5-HT 2C , all of which share considerable sequence homology (Ͼ80% in transmembrane spanning regions) and activate common signaling pathways, including G q ␣-mediated stimulation of phospholipase-C␤, elevation of intracellular inositol phosphates, and elevation of intracellular calciu