Uptake and Biological Impacts of Miroplastics and Nanoplastics in Sea Squirts

Microplastics have been detected in all marine regions and habitats, from the poles to the deep seas. A number of marine species are known to ingest microplastics, resulting in detrimental impacts. Preliminary work carried out on sea squirts suggested that microplastics may have a negative impact upon their health. Here, the solitary sea squirt, Ciona intestinalis, is used as a model species to observe the impacts of microplastics on sea squirts. This species has a transparent body form and is widely available in coastal waters. Laboratory exposures were carried out using a range of different microplastics; fluorescently labelled polystyrene (PS) and polyamide (PA) microbeads, polyhydroxybutyrate (PHB), low density polyethylene (LPE), polypropylene (PP), nylon fibres (NF), nylon particles (NMP) and polystyrene nanoparticles (PNP), cryo-ground polypropelyne rope fibres, rubber loom bands, high density polyethelyne (HDPE) and polyvinyl chloride (PVC). C. intestinalis ingested all but the cryo-ground rope fibres. Buoyancy is likely to have been an important factor for ingestion by C. intestinalis. Polystyrene and polyamide microbeads were ingested at all concentrations tested (100 and 500 PS beads mL-1, 500 and 1000 PA beads ml-1). However, there were significantly more PS beads in C. intestinalis at 24 hours than at 72 hours. Microplastic egestion was also observed, following ingestion plastics were found to be present in faecal matter. There was no distinct pattern of bead content within the sea squirts or surrounding water with time after removal from plastic contaminated water. C. intestinalis readily ingested microplastics of the tested size ranges, but were able to rapidly eject them without obvious detrimental effects. Wild specimens of C. intestinalis were also analysed for the presence of microplastics. A number of plastic-like particles were found to be present within these organisms, suggesting that ascidians may be susceptible to microplastic ingestion in the marine environment

Variation in performance on common content items at UK medical schools

Background: Due to differing assessment systems across UK medical schools, making meaningful cross-school comparisons on undergraduate students’ performance in knowledge tests is difficult. Ahead of the introduction of a national licensing assessment in the UK, we evaluate schools’ performances on a shared pool of “common content” knowledge test items to compare candidates at different schools and evaluate whether they would pass under different standard setting regimes. Such information can then help develop a cross-school consensus on standard setting shared content. Methods: We undertook a cross-sectional study in the academic sessions 2016-17 and 2017-18. Sixty “best of five” multiple choice ‘common content’ items were delivered each year, with five used in both years. In 2016-17 30 (of 31 eligible) medical schools undertook a mean of 52.6 items with 7,177 participants. In 2017-18 the same 30 medical schools undertook a mean of 52.8 items with 7,165 participants, creating a full sample of 14,342 medical students sitting common content prior to graduation. Using mean scores, we compared performance across items and carried out a “like-for-like” comparison of schools who used the same set of items then modelled the impact of different passing standards on these schools. Results: Schools varied substantially on candidate total score. Schools differed in their performance with large (Cohen’s d around 1) effects. A passing standard that would see 5 % of candidates at high scoring schools fail left low-scoring schools with fail rates of up to 40 %, whereas a passing standard that would see 5 % of candidates at low scoring schools fail would see virtually no candidates from high scoring schools fail. Conclusions: Candidates at different schools exhibited significant differences in scores in two separate sittings. Performance varied by enough that standards that produce realistic fail rates in one medical school may produce substantially different pass rates in other medical schools – despite identical content and the candidates being governed by the same regulator. Regardless of which hypothetical standards are “correct” as judged by experts, large institutional differences in pass rates must be explored and understood by medical educators before shared standards are applied. The study results can assist cross-school groups in developing a consensus on standard setting future licensing assessment

Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis

Weight gain during treatment for a cystic fibrosis exacerbation http://ow.ly/f1zl30dU9AO

A Dynamic Ocean Management Tool to Reduce Bycatch and Support Sustainable Fisheries

Seafood is anessential sourceofprotein formore than3billionpeopleworldwide, yet bycatchof threatened species in capture fisheries remains a major impediment to fisheries sustainability. Management measures designed to reduce bycatch often result in significant economic losses and even fisheries closures. Static spatial management approaches can also be rendered ineffective by environmental variability and climate change, as productive habitats shift and introduce new interactions between human activities and protected species. We introduce a new multispecies and dynamic approach that uses daily satellite data to track ocean features and aligns scales of management, species movement, and fisheries. To accomplish this, we create species distribution models for one target species and three bycatch-sensitive species using both satellite telemetry and fisheries observer data. We then integrate species-specific probabilities of occurrence into a single predictive surface, weighing the contribution of each species by management concern. We find that dynamic closures could be 2 to 10 times smaller than existing static closures while still providing adequate protection of endangered nontarget species. Our results highlight the opportunity to implement near real time management strategies that would both support economically viable fisheries and meet mandated conservation objectives in the face of changing ocean conditions. With recent advances in eco-informatics, dynamic management provides a new climate-ready approach to support sustainable fisheries

Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis

ABSTRACT Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection. A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable. Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability ( p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline ( p=0.02) and NHQ concentrations (p<0.01) decreased significantly. In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Regulators of yeast endocytosis identified by systematic quantitative analysis

Endocytosis of receptors at the plasma membrane is controlled by a complex mechanism that includes clathrin, adaptors, and actin regulators. Many of these proteins are conserved in yeast yet lack observable mutant phenotypes, which suggests that yeast endocytosis may be subject to different regulatory mechanisms. Here, we have systematically defined genes required for internalization using a quantitative genome-wide screen that monitors localization of the yeast vesicle-associated membrane protein (VAMP)/synaptobrevin homologue Snc1. Genetic interaction mapping was used to place these genes into functional modules containing known and novel endocytic regulators, and cargo selectivity was evaluated by an array-based comparative analysis. We demonstrate that clathrin and the yeast AP180 clathrin adaptor proteins have a cargo-specific role in Snc1 internalization. We additionally identify low dye binding 17 (LDB17) as a novel conserved component of the endocytic machinery. Ldb17 is recruited to cortical actin patches before actin polymerization and regulates normal coat dynamics and actin assembly. Our findings highlight the conserved machinery and reveal novel mechanisms that underlie endocytic internalization

Transplantation of Neuronal-Primed Human Bone Marrow Mesenchymal Stem Cells in Hemiparkinsonian Rodents

Bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF), and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF) method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation) were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for improving hMSC survival and engraftment

Internet and Telephone Support for Discontinuing Long-Term Antidepressants: The REDUCE Cluster Randomized Trial

Importance: There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective: To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone. Design, Setting, and Participants: In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented. Interventions: Internet and telephone self-management support, codesigned and coproduced with patients and practitioners. Main Outcomes and Measures: The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis. Results: Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events. Conclusions and Relevance: In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue. Trial Registration: ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial)