Painful Subjects, Desiring Relief: Experiencing and Governing Pain in a Medical Cannabis Program.

Cannabis can provide patients benefits for pain and symptom management, improve their functionality, and enhance their well-being. Yet restrictive medical cannabis programs can limit these potential benefits. This article draws on four years of research into Minnesota's medical cannabis program-one of the most restrictive in the United States-including in-depth interviews with patients and a survey of health care professionals.

Identification of hyaluronic acid in seized samples by Hypercarb chromatography-high resolution mass spectrometry.

Hyaluronic acid (HA) has been commonly used to treat osteoarthritis and joint injuries in horses and dogs since the 1970s. HA is a polysaccharide made up of alternating N-acetyl-d-glucosamine and d-glucuronic acid residues, with polymeric molecules achieving molecular weights as high as 20 MDa. High molecular weight HA forms a viscous hydrogel when dissolved in water, making HA solutions distinct from most other pharmaceutical preparations.

The detection of ACTH and insulin in equine plasma by solid-phase extraction and micro-flow LC/MSMS.

Previous liquid chromatography/mass spectrometry (LC/MS) methods for the detection of insulin and other similar peptide hormones in equine plasma relied on the use of antibody affinity extraction. As a result, these methods were not suitable for routine high-throughput analysis. A solid-phase extraction (SPE) method incorporating size exclusion as well as reversed-phase interactions allows the selective extraction of peptide hormones such as adrenocorticotropic hormone (ACTH), insulin and their synthetic analogues from equine plasma with approximately 80% extraction efficiencies.

Flp/-mediated disruption of and in sporozoites inhibits liver-stage development.

causes severe malaria and assembles a protein translocon (PTEX) complex at the parasitophorous vacuole membrane (PVM) of infected erythrocytes, through which several hundred proteins are exported to facilitate growth. The preceding liver stage of infection involves growth in a hepatocyte-derived PVM; however, the importance of protein export during liver infection remains unexplored. Here, we use the FlpL/ system to conditionally excise genes in sporozoites for functional liver-stage studies.

Techniques for improving the specificity of sandwich enzyme-linked immunosorbent assay-based drug screening.

ELISA assays are commonly used for drug screening by racing laboratories but are known to suffer from limited specificity. Inaccurate ELISA screening results are typically produced by non-specific antibody interactions or by the retention of chromogenic material in the sample well due to sample degradation. While confirmation of drug positives can be achieved by mass spectrometry, the follow-up of inaccurate ELISA screening results represents an unnecessary cost in staff time and reagents.

Aryl Annulation: A Powerful Simplifying Retrosynthetic Disconnection.

Retrosynthetic deconstruction of a core aromatic ring is an especially simplifying retrosynthetic step, reducing the complexity of the precursor synthetic target. Moreover, when implemented to provide a penultimate intermediate, it enables late-stage divergent aryl introductions, permitting deep-seated core aryl modifications ordinarily accessible only by independent synthesis. Herein, we highlight the use of a ketone carbonyl group as the functionality to direct such late-stage divergent aryl introductions onto a penultimate intermediate with a projected application in the total synthesis of vinblastine and its presently inaccessible analogs containing indole replacements.

Integrated social-ecological data for regional natural resource management.

Natural resource managers need information about both human and natural systems and interactions between those systems. Much data is available, but mostly from disparate sources and data have often been collected at different time steps and at different geographic scales. We used insights from the literature to select 270 relevant variables, available at national scale, from 33 unique (Australian) data sources.

Age- and dose-dependent susceptibility of axolotls (Ambystoma mexicanum) by bath exposure to Ambystoma tigrinum virus (ATV).

Ranaviruses are large, dsDNA viruses that have significant ecological and economic impact on cold-blooded vertebrates. However, our understanding of the viral proteins and subsequent host immune response(s) that impact susceptibility to infection and disease is not clear. The ranavirus Ambystoma tigrinum virus (ATV), originally isolated from the Sonoran tiger salamander (Ambystoma mavortium stebbinsi), is highly pathogenic at low doses of ATV at all tiger salamander life stages and this model has been used to explore the host-pathogen interactions of ATV infection.

Detection of gonadotropin-releasing hormone and its analogues in equine and canine urine by high-resolution data-independent acquisition.

Gonadotropin-releasing hormone (GnRH) and its synthetic analogues are considered banned substances by the racing industry. GnRH is used as a pharmaceutical to regulate the female oestrous cycle, but the hormone is also thought to increase the production of testosterone in male animals. Using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS) and data-independent acquisition (DIA), a method is presented for the detection of intact and truncated peptides of GnRH and its analogues down to the low picogram level in equine urine.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

Objectives: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH).

Design: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence.

Distinguishing appropriate from inappropriate conditions on research participation.

Individuals do not have a right to participate in clinical trials. But, they do have a right against being denied participation for inappropriate reasons. Despite the widespread endorsement of these two claims, there has been little discussion regarding which conditions for participation in clinical trials are appropriate and which are inappropriate.

Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles From Plasmodium vivax Liver Hypnozoite Infections.

Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites.

Medicalising the menace? The symbiotic convergence of medicine and law enforcement in the medicalisation of marijuana in Minnesota.

The medicalisation of marijuana has occurred rapidly, albeit nonuniformly, across the US and around the world over the past 3 decades. This paper centres on the medicalisation of marijuana in Minnesota-which has one of the most restrictive programs in the country-as a case for evaluating the negotiation of institutional boundaries with the shift from criminalisation to medicalisation after nearly a century of criminal prohibition. Drawing upon Foucauldian discourse analyses of the medical and law enforcement associations' position statements and legislative hearings that shaped medical marijuana policy in Minnesota, this paper demonstrates a symbiotic convergence between medicine and law enforcement through the deployment of shared discursive strategies in their opposition to medical marijuana that reinforce marijuana's criminalised status by solidifying the boundaries between proper medicine and dangerous drugs.

Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission.

Tryptophan C-mannosylation stabilizes proteins bearing a thrombospondin repeat (TSR) domain in metazoans. Here we show that Plasmodium falciparum expresses a DPY19 tryptophan C-mannosyltransferase in the endoplasmic reticulum and that DPY19-deficiency abolishes C-glycosylation, destabilizes members of the TRAP adhesin family and inhibits transmission to mosquitoes. Imaging P.

Compulsory Research in Learning Health Care: Against a Minimal Risk Limit.

Existing calls to implement learning health care systems have tended to stipulate a minimal or near-minimal risk limit for compulsory learning activities. I argue to the contrary that such a limit cannot be defended. So long as the way in which patients are compelled to participate in learning activities is solely through the withholding of nonresearch options for receiving care, compelling participation does not violate any individual's rights and can be both efficient and adequately fair.

Payment is a benefit and why it matters for pediatric trials.

Alan Wertheimer has argued persuasively that research ethics committees should be willing to count payment as a benefit when evaluating studies' risk-benefit ratios. In this paper, I begin by first recapitulating his argument and adding my own, complementary one. I then do two further things.

Defining the specificity of recombinant human erythropoietin confirmation in equine samples by liquid chromatography-tandem mass spectrometry.

The proteotypic human EPO peptides YLLEAK (T4), SLTTLLR (T11), TITADTFR (T14), and VYSNFLR (T17) are often used to confirm the presence of recombinant human EPO (rhEPO) in equine samples. Each of these peptides contains one or more isomeric leucine or isoleucine amino acids, raising the possibility that a simple leucine/isoleucine substitution could lead to a false identification when compared with a rhEPO reference standard. To examine this possibility variants of these four peptides were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

A new model to deliver scheduled outpatient care.

Here we describe an integrated model for scheduled care (the 'cluster clinic'). Following a pilot in April 2018, cluster clinics were established across Aberdeen City from April 2019 but not the area surrounding Aberdeen (ie, Aberdeenshire). There were 2360 referrals in 2017/2018 (pre-cluster clinic), and 2615 in 2019/2020 (post-Aberdeen City cluster clinics).

Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites.

The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria.

Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity.

Malaria is a devastating disease caused by Plasmodium parasites. Emerging resistance against current antimalarial therapeutics has engendered the need to develop antimalarials with novel structural classes. We recently described the identification and initial optimization of the 2-anilino quinazoline antimalarial class.