The effects of ethanol on the brain are concentration dependent. Low concentrations (mM) intoxicate, while greater than 100 mM anaesthetize. Of most relevance to human alcohol addiction are mechanisms of intoxication. Previously, Caenorhabditis elegans has been employed in genetic screens to define effectors of intoxication. Here, we inform interpretation of these studies by providing evidence that ethanol rapidly equilibriates across C. elegans cuticle. Importantly, the effect of ethanol on muscle activity rapidly reaches steady-state, and the concentration-dependence of the effect is very similar in intact animals and exposed muscle. Thus the cuticle does not present an absorption barrier for ethanol, and furthermore the internal concentration is likely to approach that applied externally. Thus, modelling intoxication in C. elegans requires exposure to external ethanol less than 100 mM. Furthermore, the permeability of the cuticle to ethanol enables analysis of precisely controlled concentration-dependent effects of acute, chronic, and episodic ethanol exposure on behaviour.

Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of ‘withdrawal relief’ provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits. We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity. The paradigm employs a ‘food race assay’ which tests sensorimotor performance of animals acutely and chronically treated with ethanol. We describe a multifaceted C. elegans ‘withdrawal syndrome’. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural state. However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity. The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol). This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect. These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF), opioids, tachykinins as well as NPY. This suggests an evolutionarily conserved role for neuropeptides in ethanol-induced plasticity and opens the way for a genetic analysis of the effects of alcohol on a simple model system.

Since glycoproteins have become increasingly recognized as key players in a wide variety of disease processes, there is an increasing need for advanced affinity materials for highly selective glycoprotein binding. Herein, for the first time, a surface-initiated controlled radical polymerization is integrated with supramolecular templating and molecular imprinting to yield highly reproducible synthetic recognition sites on surfaces with dissociation constants (KD) in the low micromolar range for target glycoproteins and minimal binding to nontarget glycoproteins. Importantly, it is shown that the synthetic strategy has a remarkable ability to distinguish the glycosylated and nonglycosylated forms of the same glycoprotein, with a >5-fold difference in binding affinity. The precise control over the polymer film thickness and positioning of multiple carbohydrate receptors plays a crucial role in achieving an enhanced affinity and selectivity. The generated functional materials of unprecedented glycoprotein recognition performance open up a wealth of opportunities in the biotechnological and biomedical fields.

No abstract

AimsClinical Simulation sessions were started in April 2020 to supplement reduced patient contact for medical students at the University of Sheffield due to COVID-19 restrictions. These were run by Foundation Trainees in psychiatry with supervision and oversight from a senior psychiatrist. This study aims to review current literature on remote teaching as a learning resource and will evaluate the effectiveness of clinical simulation as an alternative to patient contact, with the focus being on improving students’ confidence as well as developing clinical interview skills.MethodFeedback surveys were developed, focussing on confidence undertaking difficult aspects of psychiatric interviews, and distributed amongst two cohorts of medical students at the University of Sheffield. One cohort completed their face-to-face psychiatry placement in full pre-COVID, the other undertook placements consisting of virtual simulation sessions alongside reduced patient contact. Responses were collected online over 6 weeks between February and March 2021. As two medical students who completed face-to-face psychiatry placement prior to the pandemic, we have additionally submitted personal reflections as a comparator to current student experiences.ResultA total of 8 students in the clinical simulation cohort, and a total of 13 students from the face-to-face teaching cohort completed the questionnaire. 62.5% of students that responded were female and the remaining percentage identified as male. Students in the face-to-face cohort reported being more confident in 6 out of 7 aspects of our feedback surveys determining confidence undertaking clinical interview skills in comparison to the virtual simulation cohort. Students attended varying numbers of simulation sessions and ultimately the main restrictions and barriers to the simulation teaching reported by students are the time constraints during the sessions, and unstable internet connection.ConclusionOverall confidence levels in medical students are undoubtedly higher in students that completed full face-to-face placements in comparison to those with combined teaching. Based on student responses and review of current literature, clinical simulation appears to serve as a useful adjunct to students with reduced face-to-face contact in psychiatry, particularly for increasing confidence when interviewing more challenging patients. Immediate facilitator feedback and exposure to more difficult patient scenarios seem to be the most beneficial aspects. We would not advocate it as an exclusive form of teaching for medical students, but it may be a useful resource post-pandemic for providing students with extra learning opportunities, specifically targeted at developing confidence and skills in more difficult situations which will hopefully benefit them in their later careers.