European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the “Role of pancreas machine perfusion to increase the donor pool for beta cell replacement,” the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.</p

Intercultural Education through Religious Studies (IERS): COMENIUS Multilateral project

[EN] Religious and cultural diversity are today more than ever a critical and political challenge as the recent emergencies related to geo-political and economical global transformations clearly show. European countries are concerned by a big immigration flow that demands an educational effort in order to foster the mutual understanding and integration. According to Toledo guiding principles, IERS project meets the needs of an innovative approach in teaching about religions and beliefs at school by providing teachers of humanistic disciplines with new tools that help teachers and pupils to plunge deeper into religions and cultures of non-european countries, as well as raising the knowledge of the religious traditions that contributed to the common European cultural Identity, promoting it in the best way suited for encourage intra -and extra- European cultural dialogue attitudes. The Project aims to support the development of social, civic and intercultural transversal key competences by educating towards a positive understanding of cultural and religious differences, a readiness to engage in dialogue and to avoid or manage conflicts. By encouraging teachers and pupils to expose themselves to the differences and commonalities of religious topics, it promotes also the values of democracy, equality and human rights as it deals with social and civic dimensions of both intercultural and interreligious dialogue. The project will involve high school in-service teachers by developing a complete set of didactical tools and training experiences. The results will be: 1. A baseline study which analyzes the actual situation of teaching about religions throughout Europe; 2. New innovative didactic tools such as Multimedia Digital Modules to be used in classroom activities, accompanied by a Handbook with didactical guidelines for teachers. 3. Teacher support activities (virtual community, training activities, developing of didactical projects to apply in classroom)

Arterial ligation in the context of living donor nephrectomy: Which device to employ? Experience feedback on an automatic vascular clamp

International audienceThe choice of arterial ligation modality in the context of nephrectomies for living kidney donation poses a significant challenge. Due to the contraindication of Hem-O-Lock™ clips for this indication and the discontinuation of certain commercially available ligature devices suitable for this purpose, this issue remains particularly relevant. We report a serious adverse event with an arterial ligation device (Signia™ Stapling System, Medtronic, Dublin, Ireland). We observed intraoperative dislodgement of clips from the stump of the renal artery, resulting in significant bleeding and necessitating an emergency conversion to a subcostal approach. The experiential insights from each transplantation team regarding ligation modalities and the rigorous evaluation of medical devices are crucial imperative to ensure the donor's safety

HBZ, a new important player in the mystery of adult T-cell leukemia.

Adult T-cell leukemia (ATL) was first described in 1977. A link between ATL and human T-cell leukemia virus type 1 (HTLV-1) was clearly established in the early 1980s. Over the years, many aspects of HTLV-1-induced cellular dysfunctions have been clarified. However, the detailed mechanism behind ATL occurrence remains unsolved. Presently, we are still unable to explain the absence of viral Tax protein (thought to play a central role in T-cell transformation) in more than 50% of ATL cells. A novel HTLV-1 HBZ protein, encoded on the negative strand, was characterized by our group and is currently the subject of intensive research efforts to determine its function in viral replication and/or pathophysiology. Recently, 4 studies reported on the existence of different HBZ isoforms and have investigated on their function in both ATL cells or animal models. One report suggests that the HBZ gene might have a bimodal function (at the mRNA and protein levels), which could represent an uncharacterized strategy to regulate viral replication and proliferation of infected T cells

Sterile Pancreas Inflammation during Preservation and after Transplantation

International audienceThe pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response

Artificial Intelligence: Ready To Pass the European Board Examinations in Urology?

The role of artificial intelligence (AI) in the medical domain is increasing on an annual basis. AI allows instant access to the latest scientific data in urological surgery, facilitating a level of theoretical knowledge that previously required several years of practice and training. To evaluate the capability of AI to provide robust data in a specialized domain, we submitted the in-service assessment of the European Board of Urology to three different AI tools: ChatGPT 3.5, ChatGPT 4.0, and Bard. The assessment consists of 100 single-answer questions with four multiple-choice options. We compared the responses of 736 participants to the AI responses. The average score for the 736 participants was 67.20. ChatGPT 3.5 scored 59 points, ranking in 570th place. ChatGPT 4.0 scored 80 points, ranking 80th, just on the border of the top 10%. Google Bard scored 68 points, ranking 340th. Our study demonstrates that AI systems have the capability to participate in a urological examination and achieve satisfactory results. However, a critical perspective must be maintained, as current AI systems are not infallible. Finally, the role of AI in the acquisition of knowledge and the dissemination of information remains to be delineated. Patient summary: We submitted questions from the European Diploma in Urological Surgery to three artificial intelligence (AI) systems. Our findings reveal that AI tools show remarkable performance in assessments of urological surgical knowledge. However, certain limitations were also observed

Polarized expression of the membrane ASP protein derived from HIV-1 antisense transcription in T cells

Abstract Background Retroviral gene expression generally depends on a full-length transcript that initiates in the 5' LTR, which is either left unspliced or alternatively spliced. We and others have demonstrated the existence of antisense transcription initiating in the 3' LTR in human lymphotropic retroviruses, including HTLV-1, HTLV-2, and HIV-1. Such transcripts have been postulated to encode antisense proteins important for the establishment of viral infections. The antisense strand of the HIV-1 proviral DNA contains an ORF termed asp, coding for a highly hydrophobic protein. However, although anti-ASP antibodies have been described to be present in HIV-1-infected patients, its in vivo expression requires further support. The objective of this present study was to clearly demonstrate that ASP is effectively expressed in infected T cells and to provide a better characterization of its subcellular localization. Results We first investigated the subcellular localization of ASP by transfecting Jurkat T cells with vectors expressing ASP tagged with the Flag epitope to its N-terminus. Using immunofluorescence microscopy, we found that ASP localized to the plasma membrane in transfected Jurkat T cells, but with different staining patterns. In addition to an entire distribution to the plasma membrane, ASP showed an asymmetric localization and could also be detected in membrane connections between two cells. We then infected Jurkat T cells with NL4.3 virus coding for ASP tagged with the Flag epitope at its C-terminal end. By this approach, we were capable of showing that ASP is effectively expressed from the HIV-1 3' LTR in infected T cells, with an asymmetric localization of the viral protein at the plasma membrane. Conclusion These results demonstrate for the first time that ASP can be detected when expressed from full-length HIV-1 proviral DNA and that its localization is consistent with Jurkat T cells overexpressing ASP.</p

Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription.

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a protein that could play a role in the development of leukemia in infected patients. Herein, we demonstrate that the complementary strand of the HTLV-2 genome also encodes a protein that we named APH-2 for "antisense protein of HTLV-2." APH-2 mRNA is spliced, polyadenylated, and initiates in the 3'-long terminal repeat at different positions. This transcript was detected in all HTLV-2-infected cell lines and short-term culture of lymphocytes obtained from HTLV-2 African patients tested and in 4 of 15 HTLV-2-infected blood donors. The APH-2 protein is 183 amino acids long, is localized in the cell nucleus, and is detected in vivo. Despite the lack of a consensus basic leucine zipper domain, APH-2 interacts with cyclic adenosine monophosphate-response element binding protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells and in cells transfected with an HTLV-2 molecular clone. Altogether, our results demonstrate the existence of an antisense strand-encoded protein in HTLV-2, which could represent an important player in the development of disorders, such as lymphocytosis, which is frequently observed in HTLV-2 patients