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There are many causes of ST-elevation on electrocardiogram (ECG). ECG changes in the setting of intra-abdominal pathology is a rare and under characterised and includes the “spiked helmet sign”. We report a rare case of the “spiked helmet sign” that presented with ST-elevation in the precordial leads due to post-operative ileus.

Background Early rehabilitation and mobilisation encompass patient-tailored interventions, delivered within intensive care, but there are few studies in children and young people within paediatric intensive care units. Objectives To explore how healthcare professionals currently practise early rehabilitation and mobilisation using qualitative and quantitative approaches; co-design the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual of early rehabilitation and mobilisation interventions, with primary and secondary patient-centred outcomes; explore feasibility and acceptability of implementing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual within three paediatric intensive care units. Design Mixed-methods feasibility with five interlinked studies (scoping review, survey, observational study, codesign workshops, feasibility study) in three phases. Setting United Kingdom paediatric intensive care units. Participants Children and young people aged 0–16 years remaining within paediatric intensive care on day 3, their parents/guardians and healthcare professionals. Interventions In Phase 3, unit-wide implementation of manualised early rehabilitation and mobilisation. Main outcome measures Phase 1 observational study: prevalence of any early rehabilitation and mobilisation on day 3. Phase 3 feasibility study: acceptability of early rehabilitation and mobilisation intervention; adverse events; acceptability of study design; acceptability of outcome measures. Data sources Searched Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, PEDro, Open grey and Cochrane CENTRAL databases. Review methods Narrative synthesis. Results In the scoping review we identified 36 full-text reports evaluating rehabilitation initiated within 7 days of paediatric intensive care unit admission, outlining non-mobility and mobility early rehabilitation and mobilisation interventions from 24 to 72 hours and delivered twice daily. With the survey, 124/191 (65%) responded from 26/29 (90%) United Kingdom paediatric intensive care units; the majority considered early rehabilitation and mobilisation a priority. The observational study followed 169 patients from 15 units; prevalence of any early rehabilitation and mobilisation on day 3 was 95.3%. We then developed a manualised early rehabilitation and mobilisation intervention informed by current evidence, experience and theory. All three sites implemented the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual successfully, recruited to target (30 patients recruited) and followed up the patients until day 30 or discharge; 21/30 parents consented to complete additional outcome measures. Limitations The findings represent the views of National Health Service staff but may not be generalisable. We were unable to conduct workshops and interviews with children, young people and parents to support the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual development due to pandemic restrictions. Conclusions A randomised controlled trial is recommended to assess the effectiveness of the manualised early rehabilitation and mobilisation intervention. Future work A definitive cluster randomised trial of early rehabilitation and mobilisation in paediatric intensive care requires selection of outcome measure and health economic evaluation. Study registration The study is registered as PROSPERO CRD42019151050. The Phase 1 observational study is registered Clinicaltrials.gov NCT04110938 (Phase 1) (registered 1 October 2019) and the Phase 3 feasibility study is registered NCT04909762 (Phase 3) (registered 2 June 2021). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/21/06) and is published in full in Health Technology Assessment; Vol. 27, No. 27. See the NIHR Funding and Awards website for further award information. Plain language summary Why study early rehabilitation and mobilisation? Early rehabilitation and mobilisation, within the first week of intensive care admission, can improve the speed of recovery from illness or injury in adults. However, there is a lack of evidence about whether critically unwell children benefit from early rehabilitation and mobilisation. What did we want to find out? We aimed to identify which patients may benefit from early rehabilitation and mobilisation. Also, to develop and test a manual of early rehabilitation and mobilisation using the best evidence and expertise – called the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual. Then evaluate whether the manual could be implemented safely in paediatric intensive care units and was acceptable to staff and families. What did we do? We undertook in respect of early rehabilitation and mobilisation: review of existing research; national survey of practice (124 staff); gathered information about current conduct (15 paediatric intensive care units, 169 patients); spoke to experts (18 people); developed the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual to guide paediatric intensive care unit staff; Tested the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual in three paediatric intensive care units with 30 patients; gathered feedback from healthcare professionals via weekly ‘debriefs’ (47), interviews (13) and surveys (118), and from parents via parent-completed questionnaires (21) and interviews (14). What did we find? Despite being regarded as important, currently early rehabilitation and mobilisation practice is inconsistent, not considered ‘early’ enough and often focuses on low-risk activities conducted on the bed. Introducing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual as part of a trial was acceptable and feasible and helps standardise delivery to unwell children. Measuring child and parent reported outcomes was acceptable but follow-up at 30 days was incomplete. What does this mean? A larger trial of early rehabilitation and mobilisation, involving more paediatric intensive care units, is feasible and required to demonstrate benefit to children. Scientific summary Background Annually in the UK, 20,000 children (0–

A seldom-collected terrestrial snail, Guppya sterkii (Dall, 1888), is recorded for the first time from an older-growth hardwood forest in rural Ottawa, eastern Ontario. This represents a range extension of roughly 175 km north-east of the nearest previously known occurrence. Its conservation status and possible threats are briefly discussed.

Objectives: To re-assess the perceived benefit and relevance of simulation sessions to Victorian urology trainees and to identify areas for potential improvement. Subjects and methods: All trainees attending skills training sessions between 2011 and 2016 were asked to complete a structured questionnaire at the completion of the session. The questionnaire included 11 topic areas ranging from the year of surgical training to degree of usefulness of the session, including several sections for free-text response to offer more detailed feedback. Sessions were examined both individually and collectively to assess end-user satisfaction with the structure and content of the program. Results: In total, 24 individual skills sessions were held over the 6-year period, with a total of 355 attendees. Of these, 331 attendees completed the majority of the questionnaire, a response rate of over 93%. Overall 88% of the surveyed attendees stated that they had both the support of their supervising consultant and the flexibility of workload to attend the session; 90% of trainees felt that there was adequate reading material provided prior to the skills session, an improvement from 76% in the previous study period; and 97% of those surveyed felt that the existing session structure was appropriate and the same proportion found the sessions both useful and interesting, compared with just 63% in the previous study period. Analysis of individual topics demonstrates some variability in outcome measures, but for nearly every assessed parameter, greater than 90% of participants agreed that the session fulfilled the expected criteria. New topics developed since the 2011 analysis, including renal transplant and vascular repair, also had high levels of satisfaction. The practical models used have been refined and achieved higher scores than those in the previous assessment period. Conclusion: The urology skills-based training program has been well received by the surveyed trainees and is now embedded and accepted as part of the Victorian training program. The format of the sessions has matured and the overall rating, both individually and collectively, was high. There has been a clear increase in satisfaction across most areas assessed when compared with previous feedback. Despite this, there remain areas that can be improved, such as the amount and quality of available equipment and the inclusion of video demonstrations of operative techniques.

From 2009–2014, incidental collections of terrestrial molluscs were made from the Far North of Ontario, Canada. Thirty-four species of terrestrial molluscs were identified from these collections, including one exotic species, Deroceras reticulatum, and three newly reported species from the Far North, Vallonia pulchella, Vertigo cf. genesii, and Gastrocopta similis. Vertigo cf. genesii is newly reported from Ontario. Some species have not been collected in Ontario for many years and some of these only once before. Subnational conservation ranks are discussed for higher-ranked species.

Xerolenta obvia is a Central European land snail that is introduced to Ontario, Canada, where it was first recorded in the literature in 1975 from a single population at Bethany (City of Kawartha Lakes). Over the four decades since that publication, additional records have been found clustered near Bethany, within the City of Kawartha Lakes, and in neighbouring Peterborough County and the Regional Municipality of Durham. Two distant sites are also now known, one in rural Ottawa (southeastern Ontario), and one at Windsor, Essex County (southwestern Ontario).

There are few studies on the terrestrial molluscs of the Great Plains of Alberta. Nearly all previously published surveys have focused on the faunas of the Rocky Mountain Foothills, the Cypress Hills, the Parklands of Central Alberta, or the boreal forests. By means of hand-picking and litter samples, we surveyed for the first time the terrestrial snail fauna in the Writing-on-Stone Provincial Park, southern Alberta, Canada. From among the hoodoos (weathered rock formations) and along the cliffs on the north side of the Milk River, we found terrestrial snails at four of our five sites within the hot, dry valley of the river. Our study confirms our assumptions that the terrestrial snail fauna in these hostile habitats lacks diversity.

The geographic distribution and habitat of Patera appressa (Say, 1821) in Canada are described. This is a North American land snail native to the southern Appalachians but it has been known, since 1994, from a cluster of sites in Trenton, City of Quinte West, Ontario, where it is presumably introduced. It may no longer be extant at any of the known Ontario sites.

The minute land snail, Carychium minimum Müller, 1774 is reported from New Brunswick, Canada. This new record further adds additional data to support the supposition that this introduced, European species is probably more widespread over temperate North America than currently known.

The geographic distribution of Strobilops aeneus Pilsbry, 1926, a rare species in Canada, is reviewed and all known records are mapped. Two recent records, the only ones since 1941, are reported from the province of Ontario. One of these records represents a small range extension ca. 85 km north of the closest previous site. Specimens identified as S. aeneus from Ontario, New Brunswick, and Nova Scotia were re-examined and found to be another species.

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The introduced European slug Deroceras invadens Reise, Hutchinson, Schunack & Schlitt, 2011 is here reported from St. John’s, Newfoundland. This new record is the first from the island of Newfoundland, the Canadian province of Newfoundland and Labrador, and from Atlantic Canada. It is the first verified record for this species living outside of greenhouses in eastern Canada.

Background: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. Methods: Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). Results: Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. Conclusion: Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.

In this study, chondrogenic potentials of 3D high-density cultures of Bone Marrow (BM) and Wharton’s Jelly (WJ)-derived mesenchymal stromal cells (MSCs) was investigated by chondrogenesis- and cytokine-related gene expression over a 16-day culture period supplemented with human transforming growth factor (hTGF)-β1 at 10 ng/ml. In BM-MSC 3D models, a marked upregulation of chondrogenesis-related genes, such as SOX9, COL2A1, and ACAN (all p < 0.05) and formation of spherical pellets with structured type II collagen fibers were observed. Similarly, WJ-based high-density culture appeared higher in size and more regular in shape, with a significant overexpression of COL2A1 and ACAN (all p < 0.05) at day 16. Moreover, a similar upregulation trend was documented for IL-6 and IL-10 expression in both BM and WJ 3D systems. In conclusion, MSC-based high-density cultures can be considered a promising in vitro model of cartilage regeneration and tissue engineering. Moreover, our data support the use of WJ-MSCs as a valid alternative for chondrogenic commitment of stem cells in regenerative medicine.

Cells respond to reduced oxygen availability predominately by activation of the hypoxia-inducible factor (HIF) pathway. HIF activation upregulates hundreds of genes that help cells survive in the reduced oxygen environment. The aim of this study is to determine whether chemical-induced HIF accumulation mimics all aspects of the hypoxic response of cells. We compared the effects of dimethyloxalylglycine (DMOG) (a HIF stabiliser) on PC12 cells cultured in air oxygen (20.9% O2, AO) with those cultured in either intermittent 20.9% O2 to 2% O2 (IH) or constant 2% O2 (CN). Cell viability, cell cycle, HIF accumulation, reactive oxygen species (ROS) formation, mitochondrial function and differentiation were used to characterise the PC12 cells and evaluate the impact of DMOG. IH and CN culture reduced the increase in cell numbers after 72 and 96 h and MTT activity after 48 h compared to AO culture. Further, DMOG supplementation in AO induced a dose-dependent reduction in the increase in PC12 cell numbers and MTT activity. IH-cultured PC12 cells displayed increased and sustained HIF-1 expression over 96 h. This was accompanied by increased ROS and mitochondrial burden. PC12 cells in CN displayed little changes in HIF-1 expression or ROS levels. DMOG (0.1 mM) supplementation resulted in an IH-like HIF-1 profile. The mitochondrial burden and action potential of DMOG-supplemented PC12 cells did not mirror those seen in other conditions. DMOG significantly increased S phase cell populations after 72 and 96 h. No significant effect on PC12 cell differentiation was noted with IH and CN culture without induction by nerve growth factor (NGF), while DMOG significantly increased PC12 cell differentiation with and without NGF. In conclusion, DMOG and reduced oxygen levels stabilise HIF and affect mitochondrial activity and cell behaviour. However, DMOG does not provide an accurate replication of the reduced oxygen environments.

The present work described a bio-functionalized 3D fibrous construct, as an interactive teno-inductive graft model to study tenogenic potential events of human mesenchymal stem cells collected from Wharton’s Jelly (hWJ-MSCs). The 3D-biomimetic and bioresorbable scaffold was functionalized with nanocarriers for the local controlled delivery of a teno-inductive factor, i.e., the human Growth Differentiation factor 5 (hGDF-5). Significant results in terms of gene expression were obtained. Namely, the up-regulation of Scleraxis (350-fold, p ≤ 0.05), type I Collagen (8-fold), Decorin (2.5-fold), and Tenascin-C (1.3-fold) was detected at day 14; on the other hand, when hGDF-5 was supplemented in the external medium only (in absence of nanocarriers), a limited effect on gene expression was evident. Teno-inductive environment also induced pro-inflammatory, (IL-6 (1.6-fold), TNF (45-fold, p ≤ 0.001), and IL-12A (1.4-fold)), and anti-inflammatory (IL-10 (120-fold) and TGF-β1 (1.8-fold)) cytokine expression upregulation at day 14. The presented 3D construct opens perspectives for the study of drug controlled delivery devices to promote teno-regenerative events.

One of the most valuable functions of philosophy within the cognitive sciences and education is to help clarify important concepts, and the transfer of learning—particularly far transfer—is one such concept needing extra clarification. This is for two reasons. First, determining the psychological distance of transfer is a subjective matter depending on how similar the base and target are proposed to be which makes labeling instances of far transfer difficult. Second, current theoretical mechanisms of transfer, based on analogical reasoning structure mapping theories, struggle to explain instances of far transfer because of their commitment to structural similarity. This paper addresses these two issues by proposing an additional level of similarity—called thematic similarity—that people may use when engaging in transfer. Based on the philosophical ideas of Stephen Pepper and Gerald Holton, similarity at the thematic level is distinguished from other previously theorized levels of similarity in that it is prefigurative rather than structural. Furthermore, transfer is defined as near or far depending on the type of similarity that is involved in the transfer process rather than according to the total amount of similarity between the target and base. The paper concludes with a discussion regarding the empirical testability of these ideas.

Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.