Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin-secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non-prevascularized islet organoids. This is caused by paracrine signaling between the β-cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo, the prevascularized islet organoids are rapidly blood-perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation

Early Psychosis Intervention-Spreading Evidence-based Treatment (EPI-SET) : Protocol for an effectiveness-implementation study of a structured model of care for psychosis in youth and emerging adults

Introduction While early psychosis intervention (EPI) has proliferated in recent years amid evidence of its effectiveness, programmes often struggle to deliver consistent, recovery-based care. NAVIGATE is a manualised model of EPI with demonstrated effectiveness consisting of four components: individualised medication management, individual resiliency training, supported employment and education and family education. We aim to implement NAVIGATE in geographically diverse EPI programmes in Ontario, Canada, evaluating implementation and its effect on fidelity to the EPI model, as well as individual-level outcomes (patient/family member-reported and interviewer-rated), system-level outcomes (captured in provincial administrative databases) and engagement of participants with lived experience. Methods and analysis This is a multisite, non-randomised pragmatic hybrid effectiveness-implementation type III mixed methods study coordinated at the Centre for Addiction and Mental Health (CAMH) in Toronto. Implementation is supported by the Provincial System Support Program, a CAMH-based programme with provincial offices across Ontario, and Extension of Community Healthcare Outcomes Ontario Mental Health at CAMH and the University of Toronto. The primary outcome is fidelity to the EPI model as measured using the First Episode Psychosis Services-Fidelity Scale. Four hundred participants in the EPI programmes will be recruited and followed using both individual-level assessments and health administrative data for 2 years following NAVIGATE initiation. People with lived experience will be engaged in all aspects of the project, including through youth and family advisory committees. Ethics and dissemination Research ethics board approval has been obtained from CAMH and institutions overseeing the local EPI programmes. Study findings will be reported in scientific journal articles and shared with key stakeholders including youth, family members, programme staff and policymakers. Trial registration number NCT03919760; Pre-results

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Editorial 2022 : Inclusion of medical emergencies syllabus in our dental school curriculum

The prevention, diagnosis, and management of medical emergencies are of utmost importance in the practice of dentistry. Dental students and dental surgeons must be well trained and prepared to manage all possible medical emergencies in their daily professional practices. The team must be competent and confident in handling the initial basic emergency treatment with quality. Proper management of life-threatening medical emergencies may lead to the prevention of possible death and complications. This may also avert the psychological trauma that the healthcare professional may go through and the stigma attached to the hospital or clinic. Besides that, the ethical and legal implications of medical emergencies related to the obligations of the healthcare practitioner cannot be overlooked. The teaching of medical emergencies in our dental schools starts at the pre-clinical undergraduate level. However, the program is not well structured. Despite the consensus on the importance of training in medical emergencies, several international studies show unsatisfactory results by demonstrating low knowledge and confidence of professionals in managing medical emergencies and first aid. As a result of these international research findings, there has been aparadigm shift in teaching undergraduate students in most developed countries. The fundamental change in the approach now is emphasizing on a more competency-based curriculum and more hands-on teaching. Hence the need for a revision and inclusion of medical emergencies in our curricula in Ghana

Contract Costs Associated with Maintaining Flexible Ureteroscopes: A Single Center Experience

© 2017 American Urological Association Education and Research, Inc. Introduction We compared the cost of flexible ureteroscope processing and maintenance contracts offered by a scope manufacturer and a third-party company. Methods Use and repairs of the Storz 11278AU1 Flex X2 Flexible Ureteroscope are prospectively recorded at our large, 371-bed, acute care hospital. A retrospective analysis of the processing of ureteroscopic instruments during a 3-year period (2011 to 2013) was completed. We compared the handling of ureteroscopes between 1 year under a third-party contractor (Integrated Medical Systems International, Inc. [IMS]) and 2 prior years under the manufacturer (KARL STORZ) contract. Results From January 1, 2011 through October 1, 2012 our institution used the manufacturer for the processing of ureteroscopic instruments. From January 1, 2013 through December 9, 2013 our institution used the third-party contractor IMS for repairs. The number of procedures performed per repair/exchange during the manufacturer contract was 19.9 and the number of procedures performed per repair/exchange during the third-party contract was 11. The third-party contract resulted in a reduction of procedures performed per repair/exchange by 52%. Adjusted for inflation, the yearly cost of ureteroscope repairs was $125,715 during the manufacturer contract and$158,040 during the third-party contract. By analyzing the costs incurred in 2013, if our institution had maintained the manufacturer contract for all 3 years, the estimated repair cost would have resulted in a savings of $32,325. Conclusions Using the manufacturer repair contract is more cost-effective than using that of third-party companies

Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin-secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non-prevascularized islet organoids. This is caused by paracrine signaling between the β-cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo, the prevascularized islet organoids are rapidly blood-perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation