Intensive care utilisation after elective surgery in Australia and New Zealand: A point prevalence study.

Objective: We aimed to describe the characteristics, outcomes and resource utilisation of patients being cared for in an ICU after undergoing elective surgery in Australia and New Zealand (ANZ). Methods: This was a point prevalence study involving 51 adult ICUs in ANZ in June 2021. Patients met inclusion criteria if they were being treated in a participating ICU on he study dates. Patients were categorised according to whether they had undergone elective surgery, admitted directly from theatre or unplanned from the ward. Descriptive and comparative analysis was performed according to the source of ICU admission. Resource utilisation was measured by Length of stay, organ support and occupied bed days. Results: 712 patients met inclusion criteria, with 172 (24%) have undergone elective surgery. Of these, 136 (19%) were admitted directly to the ICU and 36 (5.1%) were an unplanned admission from the ward. Elective surgical patients occupied 15.8% of the total ICU patient bed days, of which 44.3% were following unplanned admissions. Elective surgical patients who were an unplanned admission from the ward, compared to those admitted directly from theatre, had a higher severity of illness (AP2 17 vs 13, p<0.01), require respiratory or vasopressor support (75% vs 44%, p<0.01) and hospital mortality (16.7% vs 2.2%, p < 0.01). Conclusions: ICU resource utilisation of patients who have undergone elective surgery is substantial. Those patients admitted directly from theatre have good outcomes and low resource utilisation. Patient admitted unplanned from the ward, although fewer, were sicker, more resource intensive and had significantly worse outcomes.

Weisfeiler-Lehman goes dynamic: An analysis of the expressive power of Graph Neural Networks for attributed and dynamic graphs.

Graph Neural Networks (GNNs) are a large class of relational models for graph processing. Recent theoretical studies on the expressive power of GNNs have focused on two issues. On the one hand, it has been proven that GNNs are as powerful as the Weisfeiler-Lehman test (1-WL) in their ability to distinguish graphs. Moreover, it has been shown that the equivalence enforced by 1-WL equals unfolding equivalence. On the other hand, GNNs turned out to be universal approximators on graphs modulo the constraints enforced by 1-WL/unfolding equivalence. However, these results only apply to Static Attributed Undirected Homogeneous Graphs (SAUHG) with node attributes. In contrast, real-life applications often involve a much larger variety of graph types. In this paper, we conduct a theoretical analysis of the expressive power of GNNs for two other graph domains that are particularly interesting in practical applications, namely dynamic graphs and SAUGHs with edge attributes. Dynamic graphs are widely used in modern applications; hence, the study of the expressive capability of GNNs in this domain is essential for practical reasons and, in addition, it requires a new analyzing approach due to the difference in the architecture of dynamic GNNs compared to static ones. On the other hand, the examination of SAUHGs is of particular relevance since they act as a standard form for all graph types: it has been shown that all graph types can be transformed without loss of information to SAUHGs with both attributes on nodes and edges. This paper considers generic GNN models and appropriate 1-WL tests for those domains. Then, the known results on the expressive power of GNNs are extended to the mentioned domains: it is proven that GNNs have the same capability as the 1-WL test, the 1-WL equivalence equals unfolding equivalence and that GNNs are universal approximators modulo 1-WL/unfolding equivalence. Moreover, the proof of the approximation capability is mostly constructive and allows us to deduce hints on the architecture of GNNs that can achieve the desired approximation.

Perceived and actual value of Student-led Objective Structured Clinical Examinations.

INTRODUCTION: Student-led Objective Structured Clinical Examinations (OSCEs) provide formative learning opportunities prior to Faculty-led OSCEs. It is important to undertake quality assurance measurements of peer-led assessments because, if they are found to be unreliable and invalid, they may have detrimental impacts. The objectives of this study were to explore and evaluate Student-led OSCEs hosted by fifth-year medical students. METHODS: Student-led OSCE results were analysed to examine reliability (Cronbach's alpha). The relationship between Student-led and Faculty-led OSCEs was evaluated using linear regression. Qualitative data were acquired by survey and semi-structured interviews and were analysed using an inductive content analysis approach. RESULTS: In total, 85 (94%) of 91 eligible students consented to study participation. Student-led OSCEs had a low-moderate reliability [Cronbach alpha = 0.47 (primary care) and 0.61 (human reproduction/paediatrics) (HRH)]. A statistically significant, positive relationship between Student-led and Faculty-led OSCE results was observed. Faculty-led OSCE grades increased by 0.49 (95% CI: 0.18, 0.80) to 1.09 (95% CI: 0.67, 1.52), for each percentage increase in Student-led OSCE result. Student-led OSCE participants highly valued the authentic peer-assessed experience. Reported benefits included a reduction of perceived stress and anxiety prior to Faculty-led OSCEs, recognition of learning gaps, contribution to overall clinical competency and facilitation of collaboration between peers. DISCUSSION: Student-led OSCEs are moderately reliable and can predict Faculty-led OSCE performance. This form of near-peer assessment encourages the metacognitive process of reflective practice and can be effectively implemented to direct further study. Faculties should collaborate with their student bodies to facilitate Student-led OSCEs and offer assistance to improve the quality, and benefits, of these endeavours.

'Selection into training will always be an inexact process': A survey of Directors of Physician Education on selection into Basic Physician Training in Australia and New Zealand.

BACKGROUND: Despite being one of the largest medical specialty training programmes in Australasia, there is no standardised method for selection into Basic Physician Training (BPT), and limited data exist regarding current practices. AIMS: To address existing knowledge gaps, we aimed to create a 'snapshot' of current BPT selection practices and explore the perspectives of Directors of Physician Education (DPEs) regarding trainee selection. METHODS: An electronic survey of DPEs from adult and paediatric medicine BPT sites in Australia and New Zealand was undertaken in January-February 2022. A combination of free text, multiple-choice and yes/no answers were analysed using descriptive statistics and qualitative content analysis. RESULTS: A total of 70 responses were received, achieving a response rate of 35% (70/198). Selection practices were found to be heterogenous across BPT sites. Respondents had varying opinions regarding the utility of selection tools and desirable candidate attributes. A heavy reliance upon interviews and the reported use of subjective assessments raise concerns for selection process bias. CONCLUSION: BPT sites should critically evaluate their selection methods, and more research in this field is needed to establish best practice.

Small Molecule Ligands of the BET-like Bromodomain, SmBRD3, Affect Schistosoma mansoni Survival, Oviposition, and Development.

Schistosomiasis is a disease affecting >200 million people worldwide, but its treatment relies on a single agent, praziquantel. To investigate new avenues for schistosomiasis control, we have conducted the first systematic analysis of bromodomain-containing proteins (BCPs) in a causative species, Schistosoma mansoni. Having identified 29 putative bromodomains (BRDs) in 22 S. mansoni proteins, we selected SmBRD3, a tandem BRD-containing BCP that shows high similarity to the human bromodomain and extra terminal domain (BET) family, for further studies. Screening 697 small molecules identified the human BET BRD inhibitor I-BET726 as a ligand for SmBRD3. An X-ray crystal structure of I-BET726 bound to the second BRD of SmBRD3 [SmBRD3(2)] enabled rational design of a quinoline-based ligand (15) with an ITC Kd = 364 ± 26.3 nM for SmBRD3(2). The ethyl ester pro-drug of compound 15 (compound 22) shows substantial effects on sexually immature larval schistosomula, sexually mature adult worms, and snail-infective miracidia in ex vivo assays.

Intensive care utilisation after elective surgery in Australia and New Zealand: getting the balance right.

Of the total intensive care unit (ICU) admissions in Australia and New Zealand, 36.6% occur following an elective surgical procedure. How best to use ICU services in this setting is not clear, despite this being an expensive and resource-intensive method of care delivery. The literature relating to this area has not demonstrated a clear association between improved outcomes and routine ICU utilisation. It has, however, demonstrated that methods of care delivery in this setting vary at the local, national and international level. There is now an increased interest in how we can offer safe, efficient care to patients who need ICU-level support after elective surgery, as well as where and when that care can be offered. We had previously performed a literature review relating to ICU utilisation in the elective surgical post-operative setting. This perspective piece arises from this literature review as well as extensive clinical experience from the authors. We discuss the need for a move towards an evidence-based indication for ICU admission and how this may be achieved. We then move on to the various alternative models of care that could be offered, briefly discussing their positives and potential drawbacks. We finish by outlining the research priorities and how these might be implemented in clinical practice. Getting the balance right between ICU admission and higher acuity ward-level care for post-operative elective surgical patients is difficult. However, this is an important challenge that we as a healthcare community must be working to answer.

Intracerebral Administration of a Novel Self-Assembling Peptide Hydrogel Is Safe and Supports Cell Proliferation in Experimental Intracerebral Haemorrhage.

Intracerebral haemorrhage (ICH) is the deadliest form of stroke, but current treatment options are limited, meaning ICH survivors are often left with life-changing disabilities. The significant unmet clinical need and socioeconomic burden of ICH mean novel regenerative medicine approaches are gaining interest. To facilitate the regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In this paper, the objective was to explore whether injection of a novel self-assembling peptide hydrogel (SAPH) Alpha2 was feasible, safe and could stimulate brain tissue regeneration, in a collagenase-induced ICH model in rats. Alpha2 was administered intracerebrally at 7 days post ICH and functional outcome measures, histological markers of damage and repair and RNA-sequencing were investigated for up to 8 weeks. The hydrogel Alpha2 was safe, well-tolerated and was retained in the lesion for several weeks, where it allowed infiltration of host cells. The hydrogel had a largely neutral effect on functional outcomes and expression of angiogenic and neurogenic markers but led to increased numbers of proliferating cells. RNAseq and pathway analysis showed that ICH altered genes related to inflammatory and phagocytic pathways, and these changes were also observed after administration of hydrogel. Overall, the results show that the novel hydrogel was safe when injected intracerebrally and had no negative effects on functional outcomes but increased cell proliferation. To elicit a regenerative effect, future studies could use a functionalised hydrogel or combine it with an adjunct therapy.

Evaluating an inquiry-based learning program.

Inquiry-based learning (IBL) is a promising educational framework that is understudied in graduate medical education. To determine participant satisfaction and engagement with phases of an IBL postgraduate education program, a mixed-methods study collected data via survey statements and open-ended responses. The authors included participants attending an intensive care medicine (ICM) IBL program from May to November 2020. Quantitative outcomes included participants' satisfaction with the IBL format and impact of engagement with IBL on the learning experience. Qualitative outcomes explored determinants of engagement with IBL phases and the impact on the learning experience. Of 378 attendees, 167 submitted survey responses (44.2%). There was strong agreement relating to overall satisfaction (93.4%). Responses indicated engagement with "orientation" (94.6%), "conceptualization" (97.3%), "discussion" (91.1%), and "conclusion" (91.0%) but limited engagement with the "investigation" phase (48.1%). Greater engagement with IBL phases had positive impacts, with repeat attenders having clearer learning objectives (79.1% vs. 56.6%, P < 0.05) and enhanced learning through collaborative discussion (65.9% vs. 48.7%, P < 0.05). Qualitative analysis showed that ICM learners value active learning principles, clear objectives, and a safe environment to expand their "knowledge base." Sessions facilitated "clinically relevant learning," with application of theoretical knowledge. Learners transformed and "reframed their understanding," using the input of others' experiences. ICM learners were highly satisfied with the IBL format and reported valuable learning. Participants engaged strongly with all IBL phases except the investigation phase during the sessions. IBL facilitated learners' active construction of meaning, facilitating a constructivist approach to learning.NEW & NOTEWORTHY An inquiry-based learning (IBL) program was launched as part of a novel binational intensive care medicine education program. Postgraduate intensive care medicine practitioners participated in this education intervention, where facilitated group discussions explored core intensive care medicine concepts. Survey responses indicated overall satisfaction, engagement with the IBL format, and a constructivist approach to learning. This study provided new insights into the benefits and challenges of an IBL program in the context of practicing clinicians.

Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica.

Infection with Fasciola hepatica (liver fluke) causes fasciolosis (or fascioliasis) and poses a considerable economic as well as welfare burden to both the agricultural and animal health sectors. Here, we explore the ex vivo anthelmintic potential of synthetic derivatives of hederagenin, isolated in bulk from Hedera helix. Thirty-six compounds were initially screened against F. hepatica newly excysted juveniles (NEJs) of the Italian strain. Eleven of these compounds were active against NEJs and were selected for further study, using adult F. hepatica derived from a local abattoir (provenance unknown). From these eleven compounds, six demonstrated activity and were further assessed against immature liver flukes of the Italian strain. Subsequently, the most active compounds (n = 5) were further evaluated in ex vivo dose response experiments against adult Italian strain liver flukes. Overall, MC042 was identified as the most active molecule and the EC50 obtained from immature and adult liver fluke assays (at 24 h post co-culture) are estimated as 1.07 µM and 13.02 µM, respectively. When compared to the in vitro cytotoxicity of MDBK bovine cell line, MC042 demonstrated the highest anthelmintic selectivity (44.37 for immature and 3.64 for adult flukes). These data indicate that modified hederagenins display properties suitable for further investigations as candidate flukicides.

Chemical modulation of Schistosoma mansoni lysine specific demethylase 1 (SmLSD1) induces wide-scale biological and epigenomic changes.

Background: Schistosoma mansoni, a parasitic worm species responsible for the neglected tropical disease schistosomiasis, undergoes strict developmental regulation of gene expression that is carefully controlled by both genetic and epigenetic processes. As inhibition of S. mansoni epigenetic machinery components impairs key transitions throughout the parasite's digenetic lifecycle, a greater understanding of how epi-drugs affect molecular processes in schistosomes could lead to the development of new anthelmintics. Methods:   In vitro whole organism assays were used to assess the anti-schistosomal activity of 39 Homo sapiens Lysine Specific Demethylase 1 (HsLSD1) inhibitors on different parasite life cycle stages. Moreover, tissue-specific stains and genomic analysis shed light on the effect of these small molecules on the parasite biology. Results: Amongst this collection of small molecules, compound 33 was the most potent in reducing ex vivo viabilities of schistosomula, juveniles, miracidia and adults. At its sub-lethal concentration to adults (3.13 µM), compound 33 also significantly impacted oviposition, ovarian as well as vitellarian architecture and gonadal/neoblast stem cell proliferation. ATAC-seq analysis of adults demonstrated that compound 33 significantly affected chromatin structure (intragenic regions > intergenic regions), especially in genes differentially expressed in cell populations (e.g., germinal stem cells, hes2 + stem cell progeny, S1 cells and late female germinal cells) associated with these ex vivo phenotypes. KEGG analyses further highlighted that chromatin structure of genes associated with sugar metabolism as well as TGF-beta and Wnt signalling were also significantly perturbed by compound 33 treatment. Conclusions: This work confirms the importance of histone methylation in S. mansoni lifecycle transitions, suggesting that evaluation of LSD1 - targeting epi-drugs may facilitate the search for next-generation anti-schistosomal drugs. The ability of compound 33 to modulate chromatin structure as well as inhibit parasite survival, oviposition and stem cell proliferation warrants further investigations of this compound and its epigenetic target SmLSD1.

Key aspects of teaching that affect perceived preparedness of medical students for transition to work: insights from the COVID-19 pandemic.

BACKGROUND: The self-perceived preparedness of medical students to transition into practising junior doctors has implications for patient safety, graduate well-being and development of professional identity. AIMS: To examine the impact of changes to final-year education and placements and determine key elements that contribute to self-perceived preparedness for transition to work. METHODS: An online survey among final-year medical students at one Australian medical school in 2020 (the cohort most affected by the coronarvirus disease 2019 [COVID-19] pandemic), exploring overall self-perceived preparedness and specific competencies, including questions in previous Australian Medical Council/Medical Board of Australia annual national surveys. Quantitative and qualitative content analyses were performed. RESULTS: Thirty-three percent of eligible participants completed the survey. There was a significant decline in overall self-perceived preparedness among participants (mean preparedness, 3.55 ± 0.88) compared with 2019 graduates from the same medical school (mean preparedness, 4.28 ± 0.64, P < 0.001) and the national average (mean preparedness, 3.81 ± 0.93, P = 0.04). There was a decline in self-perceived preparedness for all specific competencies, with complex competencies more greatly affected. Qualitative content analysis of free text responses identified limitations of an online compared with a face-to-face formal education program and specific aspects of placements, which contribute to perceived preparedness. CONCLUSION: The current study highlights key aspects of clinical placements and formal teaching programs that contribute to perceptions of preparedness for transition to clinical practice. Relevant experiential learning in the clinical setting, opportunities for deliberate practice of necessary skills (in simulation and the clinical setting) and reflective opportunities from formal teaching programs contribute to perceived preparedness and are important elements to be included in the final phase of any medical program.

Using ChEMBL to Complement Schistosome Drug Discovery.

Schistosomiasis is one of the most important neglected tropical diseases. Until an effective vaccine is registered for use, the cornerstone of schistosomiasis control remains chemotherapy with praziquantel. The sustainability of this strategy is at substantial risk due to the possibility of praziquantel insensitive/resistant schistosomes developing. Considerable time and effort could be saved in the schistosome drug discovery pipeline if available functional genomics, bioinformatics, cheminformatics and phenotypic resources are systematically leveraged. Our approach, described here, outlines how schistosome-specific resources/methodologies, coupled to the open-access drug discovery database ChEMBL, can be cooperatively used to accelerate early-stage, schistosome drug discovery efforts. Our process identified seven compounds (fimepinostat, trichostatin A, NVP-BEP800, luminespib, epoxomicin, CGP60474 and staurosporine) with ex vivo anti-schistosomula potencies in the sub-micromolar range. Three of those compounds (epoxomicin, CGP60474 and staurosporine) also demonstrated potent and fast-acting ex vivo effects on adult schistosomes and completely inhibited egg production. ChEMBL toxicity data were also leveraged to provide further support for progressing CGP60474 (as well as luminespib and TAE684) as a novel anti-schistosomal compound. As very few compounds are currently at the advanced stages of the anti-schistosomal pipeline, our approaches highlight a strategy by which new chemical matter can be identified and quickly progressed through preclinical development.

A scoping review of patient-led teaching of health professions students.

Patients with chronic health conditions may become experts in their own conditions. Thus, utilising patients as teachers, with autonomy over taught content, may better prepare students to deliver patient-centred care. A scoping review following Arksey and O'Malley and Joanna Briggs Institute framework was performed. A total of 2162 articles were identified and 28 unique studies were included. Patient teacher programmes range from single, short 1- to 2-h tutorials to longitudinal community-based programmes. These programmes are mutually beneficial for students, improving awareness of all patient-centred domains, and patients feel empowered by their roles in education.

Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogens.

Professionalism and clinical short answer question marking with machine learning.

Machine learning may assist in medical student evaluation. This study involved scoring short answer questions administered at three centres. Bidirectional encoder representations from transformers were particularly effective for professionalism question scoring (accuracy ranging from 41.6% to 92.5%). In the scoring of 3-mark professionalism questions, as compared with clinical questions, machine learning had a lower classification accuracy (P < 0.05). The role of machine learning in medical professionalism evaluation warrants further investigation.

Systematic review: Association between circulating microRNA expression & stroke.

This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of microRNA expression in the diagnosis and prognosis of ischaemic or haemorrhagic stroke. Electronic databases were searched from 1993 to October 2021, using key words relevant to concepts of stroke and microRNA. Studies that met specific inclusion and exclusion criteria were selected for data extraction. To minimise erroneous associations, findings were restricted to microRNAs reported to change in more than two independent studies. Of the papers assessed, 155 papers reported a change in microRNA expression observed in more than two independent studies. In ischaemic studies, two microRNAs were consistently differentially expressed in clinical samples (miR-29b & miR-146a) and four were altered in preclinical samples (miR-137, miR-146a, miR-181b & miR-223-3p). Across clinical and preclinical haemorrhagic studies, four microRNAs were downregulated consistently (miR-26a, miR-126, miR-146a & miR-155). Across included studies, miR-126 and miR-146a were the only two microRNAs to be differentially expressed in clinical and preclinical cohorts following ischaemic or haemorrhagic stroke. Further studies, employing larger populations with consistent methodologies, are required to validate the true clinical value of circulating microRNAs as biomarkers of ischaemic and haemorrhagic stroke.

Schistosoma mansoni α-N-acetylgalactosaminidase (SmNAGAL) regulates coordinated parasite movement and egg production.

α-galactosidase (α-GAL) and α-N-acetylgalactosaminidase (α-NAGAL) are two glycosyl hydrolases responsible for maintaining cellular homeostasis by regulating glycan substrates on proteins and lipids. Mutations in the human genes encoding either enzyme lead to neurological and neuromuscular impairments seen in both Fabry- and Schindler/Kanzaki- diseases. Here, we investigate whether the parasitic blood fluke Schistosoma mansoni, responsible for the neglected tropical disease schistosomiasis, also contains functionally important α-GAL and α-NAGAL proteins. As infection, parasite maturation and host interactions are all governed by carefully-regulated glycosylation processes, inhibiting S. mansoni's α-GAL and α-NAGAL activities could lead to the development of novel chemotherapeutics. Sequence and phylogenetic analyses of putative α-GAL/α-NAGAL protein types showed Smp_089290 to be the only S. mansoni protein to contain the functional amino acid residues necessary for α-GAL/α-NAGAL substrate cleavage. Both α-GAL and α-NAGAL enzymatic activities were higher in females compared to males (p<0.05; α-NAGAL > α-GAL), which was consistent with smp_089290's female biased expression. Spatial localisation of smp_089290 revealed accumulation in parenchymal cells, neuronal cells, and the vitellaria and mature vitellocytes of the adult schistosome. siRNA-mediated knockdown (>90%) of smp_089290 in adult worms significantly inhibited α-NAGAL activity when compared to control worms (siLuc treated males, p<0.01; siLuc treated females, p<0.05). No significant reductions in α-GAL activities were observed in the same extracts. Despite this, decreases in α-NAGAL activities correlated with a significant inhibition in adult worm motility as well as in egg production. Programmed CRISPR/Cas9 editing of smp_089290 in adult worms confirmed the egg reduction phenotype. Based on these results, Smp_089290 was determined to act predominantly as an α-NAGAL (hereafter termed SmNAGAL) in schistosome parasites where it participates in coordinating movement and oviposition processes. Further characterisation of SmNAGAL and other functionally important glycosyl hydrolases may lead to the development of a novel anthelmintic class of compounds.

No evidence that mask-wearing in public places elicits risk compensation behavior during the COVID-19 pandemic.

Face masks have been widely employed as a personal protective measure during the COVID-19 pandemic. However, concerns remain that masks create a false sense of security that reduces adherence to other public health measures, including social distancing. This paper tested whether mask-wearing was negatively associated with social distancing compliance. In two studies, we combined video-observational records of public mask-wearing in two Dutch cities with a natural-experimental approach to evaluate the effect of an area-based mask mandate. We found no observational evidence of an association between mask-wearing and social distancing but found a positive link between crowding and social distancing violations. Our natural-experimental analysis showed that an area-based mask mandate did not significantly affect social distancing or crowding levels. Our results alleviate the concern that mask use reduces social distancing compliance or increases crowding levels. On the other hand, crowding reduction may be a viable strategy to mitigate social distancing violations.

Face-touching behaviour as a possible correlate of mask-wearing: A video observational study of public place incidents during the COVID-19 pandemic.

Most countries in the world have recommended or mandated face masks in some or all public places during the COVID-19 pandemic. However, mask use has been thought to increase people's face-touching frequency and thus risk of self-inoculation. Across two studies, we video-observed the face-touching behaviour of members of the public in Amsterdam and Rotterdam (the Netherlands) during the first wave of the pandemic. Study 1 (n = 383) yielded evidence in favour of the absence of an association between mask-wearing and face-touching (defined as touches of face or mask), and Study 2 (n = 421) replicated this result. Secondary outcome analysis of the two studies-analysed separately and with pooled data sets-evidenced a negative association between mask-wearing and hand contact with the face and its t-zone (i.e. eyes, nose and mouth). In sum, the current findings alleviate the concern that mask-wearing has an adverse face-touching effect.

Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.

Extracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships.