RNA interference therapeutics in organ transplantation:The dawn of a new era

RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest. In 2006, the discovery of RNAi was awarded the Nobel Prize in Medicine and its success has accumulated since. Gene silencing through RNAi has been used successfully in a broad range of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Here, genes related to ischemia-reperfusion injury (IRI) or graft rejection may be silenced to improve organ quality after transplantation. Several strategies have been used to deliver siRNA, and pretransplant machine perfusion presents a unique opportunity to deliver siRNA to the target organ during ex situ preservation. In this review, the potential of RNAi in the field of organ transplantation will be discussed. A brief overview on the discovery of RNAi, its mechanism, and limitations are included. In addition, studies using RNAi to target genes related to IRI in liver, kidney, lung, and heart transplantation are discussed

The Emerging Role of Viability Testing During Liver Machine Perfusion

The transplant community continues to be challenged by the disparity between the need for liver transplantation and the shortage of suitable donor organs. At the same time, the number of unused donor livers continues to increase, most likely attributed to the worsening quality of these organs. To date, there is no reliable marker of liver graft viability that can predict good posttransplant outcomes. Ex situ machine perfusion offers additional data to assess the viability of donor livers before transplantation. Hence, livers initially considered unsuitable for transplantation can be assessed during machine perfusion in terms of appearance and consistency, hemodynamics, and metabolic and excretory function. In addition, postoperative complications such as primary nonfunction or posttransplant cholangiopathy may be predicted and avoided. A variety of viability criteria have been used in machine perfusion, and to date there is no widely accepted composition of criteria for clinical use. This review discusses potential viability markers for hepatobiliary function during machine perfusion, describes current limitations, and provides future recommendations for the use of viability criteria in clinical liver transplantation

Enhancing motivation and learning in engineering courses: a challenge-based approach to teaching embedded systems

This paper addresses an approach to teaching embedded systems programming through a challenge-based competition involving robots. This pedagogical project distinguishes itself by incorporating international students from three international institutions through the Blended Intensive Program (BIP). The research findings indicate that this approach yields excellent results regarding student engagement and learning outcomes. The challenge-based program effectively promotes students’ creative problem-solving abilities by combining theoretical instruction with hands-on experience in a competitive setting.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CeDRI (UIDB/05757/2020 and UIDP/05757/2020), SusTEC (LA/P/0007/2021) and project LA/P/0063/2020. This work was supported by Blended Intensive Programme ID: 2021- 1-PT01-KA131-HED-000004268-2, Embedded Systems Applications. The authors thank CEFET/RJ, the Institute of Engineering and the Research Centre on Bio-based Economy of Hanze University of Applied Sciences, the ERASMUS program, and the Brazilian research agencies CAPES, CNPq, and FAPERJ.info:eu-repo/semantics/publishedVersio

ORGAN THERAPEUTICS DURING EX-SITU DYNAMIC PRESERVATION. A LOOK INTO THE FUTURE

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Impact of recipient functional status on 1-year liver transplant outcomes

BACKGROUND: The Karnofsky Performance Status (KPS) scale has been widely validated for clinical practice for over 60 years.AIM: To examine the extent to which poor pre-transplant functional status, assessed using the KPS scale, is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.METHODS: This study included 38278 United States adults who underwent first, non-urgent, liver-only transplantation from 2005 to 2014 (Scientific Registry of Transplant Recipients). Functional impairment/disability was categorized as severe, moderate, or none/normal. Analyses were conducted using multivariable-adjusted Cox survival regression models.RESULTS: The median age was 56 years, 31% were women, median pre-transplant Model for End-Stage for Liver Disease score was 18. Functional impairment was present in 70%; one-quarter of the sample was severely disabled. After controlling for key recipient and donor factors, moderately and severely disabled patients had a 1-year mortality rate of 1.32 [confidence interval (CI): 1.21-1.44] and 1.73 (95%CI: 1.56-1.91) compared to patients with no impairment, respectively. Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13 (CI: 1.02-1.24) and 1.16 (CI: 1.02-1.31), respectively.CONCLUSION: Pre-transplant functional status is a useful prognostic indicator for 1-year post-transplant patient and graft survival.</p