Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage.

Ultraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mechanisms, specifically focusing on the roles of stalled RNA polymerase II, Cockayne syndrome protein B (CSB), CSA and UV-stimulated scaffold protein A (UVSSA) in TC-NER. We also discuss the intriguing role of protein ubiquitylation in this process. Additionally, we highlight key aspects of the effect of UV irradiation on transcription and describe the role of signaling cascades in orchestrating this response. Finally, we describe the pathogenic mechanisms underlying xeroderma pigmentosum and Cockayne syndrome, the two main diseases linked to mutations in NER factors.

Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Assessment of injuries patterns produced by a 9mm P.A.K "rubber ball" blank firing weapon: porcine model.

The use of less lethal weapons aims to mitigate civilian casualties caused by firearm use. However, due to numerous cases in which these weapons caused serious injuries, even lethal injuries, both legislation and the forensic field are interested in characterizing and regulating them better. In the forensic field, there is a lack of strong research about injury patterns of these weapons which makes it difficult to identify the type of weapon employed. In this study, the main objective was to characterize the injury pattern produced by the impact of the 9 mm P.A.K. projectile. A porcine model was used. Four different distances were studied: firm contact, 10 cm, 60 cm and 110 cm, using 3 of the more representative anatomical sites: the head, the hind leg and the ribs. The average measurement of the entrance orifice varied according to the anatomical site, being 6.67 mm wide and 6.25 mm long in the thorax, 7.3 mm wide and 8.8 mm long in the hind legs, and 7.62 mm wide and 7.54 mm long in the head. The variation in width and length measurements was not found to be directly related to the shot distance. The gunshot residues had similar characteristics to those of conventional lead projectiles, however there was more unburned powder deposit near the wounds, with a less dense soot and more dense powder tattoo. Depth varied widely regardless of tissue and firing distance, although loss of penetrating power and injury is observed as one moves away from the target.

Computational mesoscale framework for biological clustering and fractal aggregation.

Hierarchical clustering due to diffusion and reaction is a widespread occurrence in natural phenomena, displaying fractal behavior with non-integer size scaling. The study of this phenomenon has garnered interest in both biological systems such as morphogenesis and blood clotting, and synthetic systems such as colloids and polymers. The modeling of biological clustering can be difficult, as it can occur on a variety of scales and involve multiple mechanisms, necessitating the use of various methods to capture its behavior. Here, we propose a novel framework, the generalized-mesoscale-clustering (GMC), for the study of complex hierarchical clustering phenomena in biological systems. The GMC framework incorporates the effects of hydrodynamic interactions, bonding, and surface tension, and allows for the analysis of both static and dynamic states of cluster development. The framework is applied to a range of biological clustering mechanisms, with a focus on blood-related clustering from fibrin network formation to platelet aggregation. Our study highlights the importance of a comprehensive characterization of the structural properties of the cluster, including fractal dimension, pore-scale diffusion, initiation time, and consolidation time, in fully understanding the behavior of biological clustering systems. The GMC framework also provides the potential to investigate the temporal evolution and mechanical properties of the clusters by tracking bond density and including hydrodynamic interactions.

Computational modeling of passive transport of functionalized nanoparticles.

Functionalized nanoparticles (NPs) are complex objects present in a variety of systems ranging from synthetic grafted nanoparticles to viruses. The morphology and number of the decorating groups can vary widely between systems. Thus, the modeling of functionalized NPs typically considers simplified spherical objects as a first-order approximation. At the nanoscale label, complex hydrodynamic interactions are expected to emerge as the morphological features of the particles change, and they can be further amplified when the NPs are confined or near walls. Direct estimation of these variations can be inferred via diffusion coefficients of the NPs. However, the evaluation of the coefficients requires an improved representation of the NPs morphology to reproduce important features hidden by simplified spherical models. Here, we characterize the passive transport of free and confined functionalized nanoparticles using the Rigid Multi-Blob (RMB) method. The main advantage of RMB is its versatility to approximate the mobility of complex structures at the nanoscale with significant accuracy and reduced computational cost. In particular, we investigate the effect of functional groups' distribution, size, and morphology over nanoparticle translational and rotational diffusion. We identify that the presence of functional groups significantly affects the rotational diffusion of the nanoparticles; moreover, the morphology of the groups and number induce characteristic mobility reduction compared to non-functionalized nanoparticles. Confined NPs also evidenced important alterations in their diffusivity, with distinctive signatures in the off-diagonal contributions of the rotational diffusion. These results can be exploited in various applications, including biomedical, polymer nanocomposite fabrication, drug delivery, and imaging.

Our evolution in the treatment of hepatic artery and portal vein thrombosis in pediatric liver transplantation: Success with catheter-directed therapies.

BACKGROUND: In pediatric liver transplant recipients, hepatic artery thrombosis and portal vein thrombosis are major causes of acute graft failure and mortality within 30 days of transplantation. There is, however, a strong possibility of graft salvage if flow can be re-established to reduce ischemic injury. The current standard treatment is surgical revascularization, and if unsuccessful, retransplantation. Due to our success in treating these complications with catheter-directed therapies, we sought to summarize and publish the outcomes of all patients who experienced hepatic artery thrombosis or portal vein thrombosis within 30 days of liver transplantation. METHODS: We conducted a retrospective cohort analysis of 27 pediatric liver transplant recipients who experienced hepatic artery thrombosis (n = 13), portal vein thrombosis (n = 9), or both (n = 5) between September 2012 and March 2021. We collected and tabulated data on the patients and therapies performed to treat them, including success rates, primary and secondary patency, and clinical outcomes. RESULTS: Among these patients, 6 were managed with anticoagulation and relisting for transplant and 21 had a primary revascularization attempt. Surgical recanalization was attempted in 7 patients of which 3 had successful recanalization (43%) and catheter-directed recanalization was attempted in 14 patients with 100% success in re-establishing blood flow to the graft. Additionally, patency was increased, and mortality was decreased in patients treated with catheter-directed recanalization compared to surgical revascularization or anticoagulation alone. CONCLUSION: This data illustrates the need to further investigate catheter-directed thrombolysis as a potential first-line treatment for postoperative HAT and PVT in pediatric liver transplant recipients.

A new chapter in an evolving pandemic: Successful pediatric liver transplantation with SARS-CoV-2+ donors.

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors. METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform. RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a 16-month-old boy with cardiopulmonary arrest of unknown etiology. Three NAT tests (2 NP swab/1 BAL) prior to procurement failed to detect SARS-CoV-2. The diagnosis was made when the medical examiner repeated 2 NP swab NATs and an archive plasma NAT, all positive for SARS-CoV-2. Both 2-year-old recipients continue to do well 8 months post-transplant, with excellent graft function and no evidence of SARS-CoV-2 transmission. CONCLUSIONS: This is the first report to describe successful pediatric liver transplantation from SARS-CoV-2+ donors. These data reinforce the adult transplant experience and support the judicious use of SARS-CoV-2+ donors for liver transplantation in children. With SARS-CoV-2 becoming endemic, the concern for donor-derived viral transmission must now be weighed against the realized benefit of life-saving transplantation in the pediatric population as we continue to work toward donor pool maximization.

GSK-3 is an RNA polymerase II phospho-CTD kinase.

We have previously found that UV-induced DNA damage causes hyperphosphorylation of the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), inhibition of transcriptional elongation and changes in alternative splicing (AS) due to kinetic coupling between transcription and splicing. In an unbiased search for protein kinases involved in the AS response to DNA damage, we have identified glycogen synthase kinase 3 (GSK-3) as an unforeseen participant. Unlike Cdk9 inhibition, GSK-3 inhibition only prevents CTD hyperphosphorylation triggered by UV but not basal phosphorylation. This effect is not due to differential degradation of the phospho-CTD isoforms and can be reproduced, at the AS level, by overexpression of a kinase-dead GSK-3 dominant negative mutant. GSK-3 inhibition abrogates both the reduction in RNAPII elongation and changes in AS elicited by UV. We show that GSK-3 phosphorylates the CTD in vitro, but preferentially when the substrate is previously phosphorylated, consistently with the requirement of a priming phosphorylation reported for GSK-3 efficacy. In line with a role for GSK-3 in the response to DNA damage, GSK-3 inhibition prevents UV-induced apoptosis. In summary, we uncover a novel role for a widely studied kinase in key steps of eukaryotic transcription and pre-mRNA processing.

A DNA intercalating dye-based RT-qPCR alternative to diagnose SARS-CoV-2.

Early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proven crucial during the efforts to mitigate the effects of the COVID-19 pandemic. Several diagnostic methods have emerged in the past few months, each with different shortcomings and limitations. The current gold standard, RT-qPCR using fluorescent probes, relies on demanding equipment requirements plus the high costs of the probes and specific reaction mixes. To broaden the possibilities of reagents and thermocyclers that could be allocated towards this task, we have optimized an alternative strategy for RT-qPCR diagnosis. This is based on a widely used DNA-intercalating dye and can be implemented with several different qPCR reagents and instruments. Remarkably, the proposed qPCR method performs similarly to the broadly used TaqMan-based detection, in terms of specificity and sensitivity, thus representing a reliable tool. We think that, through enabling the use of vast range of thermocycler models and laboratory facilities for SARS-CoV-2 diagnosis, the alternative proposed here can increase dramatically the testing capability, especially in countries with limited access to costly technology and reagents.

Liver transplant in a recently COVID-19 positive child with hepatoblastoma.

We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4-year-old male with COVID-19 prior to transplant. The first negative NP swab was documented 1 month after initial diagnosis, when SARS-CoV-2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL-4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for 4 weeks, he underwent a whole-organ pediatric liver transplant. COVID-19 positivity determined via NP swab SARS-CoV-2 real-time RT-PCR (Hologic Aptima SARS-CoV-2 RT-PCR assay). IgG and IgM total SARS- CoV-2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti-SARS-CoV-2 Test. Patient received standard prednisone and tacrolimus-based immunosuppression without induction therapy following transplant. Post-transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post-transplant day #11. Surveillance tests have remained negative with persistent SARS-CoV-2 IgG antibodies at 6 weeks after transplant. We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID-19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID-19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID-19.

The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series.

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Canakinumab with and without pembrolizumab in patients with resectable non-small-cell lung cancer: CANOPY-N study design.

Canakinumab is a human IgGκ monoclonal antibody, with high affinity and specificity for IL-1ß. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) trial, evaluating canakinumab for cardiovascular disease, provided the first signal of the potential of IL-1ß inhibition on lung cancer incidence reduction. Here, we describe the rationale and design for CANOPY-N, a randomized Phase II trial evaluating IL-1ß inhibition with or without immune checkpoint inhibition as neoadjuvant treatment in patients with non-small-cell lung cancer. Patients with stage IB to IIIA non-small-cell lung cancer eligible for complete resection will receive canakinumab or pembrolizumab as monotherapy, or in combination. The primary end point is major pathological response by central review; secondary end points include overall response rate, major pathological response (local review), surgical feasibility rate and pharmacokinetics. Clinical trial registration: NCT03968419 (ClinicalTrials.gov).

Lay abstract A previous study showed that canakinumab reduced the risk of lung cancer in patients with heart disease. Canakinumab blocks an inflammatory protein called IL-1ß that is involved in cancer. Anti-cancer drugs used before surgery ('neo-adjuvant') can improve the success rate of surgery and may help prevent the cancer from returning. Neo-adjuvant trials help us understand how the drugs work and how they affect cancer. CANOPY-N (NCT03968419) is an ongoing randomized, exploratory, Phase II clinical trial testing canakinumab and pembrolizumab (a different cancer immunotherapy), alone or combined, for patients with early non-small-cell lung cancer. The study will test whether treatment can kill most cancer cells in the surgery sample ('major pathological response'). It will also investigate other effects on cancer biology, levels of molecules that measure possible clinical benefit ('biomarkers') and side effects.

Donor and transplant candidate selection for solid organ transplantation during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating donors and recipients with possible SARS-CoV-2 infection. Our current communication shares a protocol for donor and transplant recipient selection during the coronavirus disease 2019 (COVID-19) pandemic to continue lifesaving solid organ transplantation for heart, lung, liver, and kidney recipients. The initial results using this protocol are presented here and meant to encourage dialogue between providers, offering ideas to improve safety in solid organ transplantation with limited health care resources. This protocol was created utilizing the guidelines of various organizations and from the clinical experience of the authors and will continue to evolve as more is understood about SARS-CoV-2 and how it affects organ donors and transplant recipients.

Reciprocal regulation between alternative splicing and the DNA damage response.

Splicing, the process that catalyzes intron removal and flanking exon ligation, can occur in different ways (alternative splicing) in immature RNAs transcribed from a single gene. In order to adapt to a particular context, cells modulate not only the quantity but also the quality (alternative isoforms) of their transcriptome. Since 95% of the human coding genome is subjected to alternative splicing regulation, it is expected that many cellular pathways are modulated by alternative splicing, as is the case for the DNA damage response. Moreover, recent evidence demonstrates that upon a genotoxic insult, classical DNA damage response kinases such as ATM, ATR and DNA-PK orchestrate the gene expression response therefore modulating alternative splicing which, in a reciprocal way, shapes the response to a damaging agent.

Video-assisted thoracic surgery and anatomical lung resections. Where do we stand? National survey by the Spanish Society of Thoracic Surgery. / Cirugía torácica video-asistida y resecciones pulmonares anatómicas. ¿Dónde estamos? Encuesta nacional de la Sociedad Española de Cirugía Torácica.

INTRODUCTION: The objective of this survey is to find out the cumulated experience and the current situation of video-assisted thoracic surgery (VATS) for anatomical lung resections in Spain. METHODS: This is a descriptive study performed from two independent surveys designed through the Survey Monkey® web platform. The first survey was aimed at 53 thoracic surgery departments from the public and state-assisted national health system. The second survey, of a personal nature, was directed at 315 thoracic surgeons in active service, including physicians at their residency program. The surveys were kept operative from 18/11/2014 to 15/01/2015. RESULTS: The first survey was answered by 32 (60%) departments and the second by 167 (53%) professionals. A total of 29 (91%) of the thoracic surgery departments represented recognized having some level of experience in this technique. However, a great proportion of departments, 15 (52%), counted less than 100 procedures and the cumulated time of experience was lower than 5 years in 19 (66%) departments. Among all the individual respondents, 126 (77%) admitted having performed the procedure at some point. Of those without any experience, at least 36 (95%) of them recognized that future training in this technique is one of their future professional objectives. CONCLUSIONS: Waiting for future prospective national registries contribute further information about the expansion of this technique in our country, the results of the current survey show, up to now, the best reflection of clinical practice and opinion of the surgeons involved in the development of VATS.

Self-Assembled Asymmetric Block Copolymer Membranes: Bridging the Gap from Ultra- to Nanofiltration.

The self-assembly of block copolymers is an emerging strategy to produce isoporous ultrafiltration membranes. However, thus far, it has not been possible to bridge the gap from ultra- to nanofiltration and decrease the pore size of self-assembled block copolymer membranes to below 5 nm without post-treatment. It is now reported that the self-assembly of blends of two chemically interacting copolymers can lead to highly porous membranes with pore diameters as small as 1.5 nm. The membrane containing an ultraporous, 60 nm thin separation layer can fully reject solutes with molecular weights of 600 g mol(-1) in aqueous solutions with a water flux that is more than one order of magnitude higher than the permeance of commercial nanofiltration membranes. Simulations of the membrane formation process by dissipative particle dynamics (DPD) were used to explain the dramatic observed pore size reduction combined with an increase in water flux.

Transcriptional elongation and alternative splicing.

Alternative splicing has emerged as a key contributor to proteome diversity, highlighting the importance of understanding its regulation. In recent years it became apparent that splicing is predominantly cotranscriptional, allowing for crosstalk between these two nuclear processes. We discuss some of the links between transcription and splicing, with special emphasis on the role played by transcription elongation in the regulation of alternative splicing events and in particular the kinetic model of alternative splicing regulation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

Real-life benchmarking bladder cancer care: A population-based study.

INTRODUCTION: Radical cystectomy (RC) is a complex oncological surgical procedure and population studies of routine surgical care have suggested suboptimal results compared to high-volume centers of excellence. A previous Canadian bladder cancer quality-of-care consensus led to adoption of multiple key quality-of-care indicators, with associated benchmarks created using available evidence and expert opinion to inform and measure future performance. Herein, we report real-life benchmark performance for the management of muscle-invasive bladder cancer (MIBC) relative to expert opinion guidance. METHODS: This is a population-based, retrospective, cohort study that used the Ontario Cancer Registry (OCR) to identify all incident patients who underwent RC from 2009-2013. Electronic records of treatment from 1573 patients were linked to OCR; pathology records were obtained for all cases and reviewed by a team of trained data abstractors. The primary objective was to describe benchmarks for identified indicators, first as median values obtained across hospitals or providers, as well as a "pared-mean" approach to identify a benchmark population of "top performance," as defined as the best outcome accomplished for at least 10% of the population. RESULTS: Overall, performance in Ontario across all indicators fell short of expert opinion-determined benchmarks. Annual surgical volume by each surgeon performing a RC (benchmark >6, percent of institutions meeting benchmark=20%), percent of patients with MIBC referred preoperatively to medical oncology (MO; benchmark>90%, percent of institutions meeting benchmark=2%) and radiation oncology (RO; benchmark>50%, percent of institutions meeting benchmark=0%), time to cystectomy within six weeks of transurethral resection of bladder tumor (TURBT) in patients without neoadjuvant chemotherapy (benchmark <6 weeks, percent of institutions meeting benchmark=0%), percent of patients with adequate lymph node dissection (defined as >14 nodes, benchmark>85%, percent of institutions meeting benchmark=0%), percent of patients with positive margins post-RC (benchmark <10%, percent of institutions meeting benchmark=46%), and 90-day mortality (benchmark<5%, percent of institutions meeting benchmark=37%) fell considerably short. Simply evaluating benchmarks across the province as median performance significantly underestimated benchmarks that were possible by top-performing hospitals. CONCLUSIONS: Performance through most bladder cancer quality-of-care indicators fall short of benchmarks proposed by expert opinion. Different methodologies, such as a paredmean approach of top performers, may provide more realistic benchmarking.

The carbon footprint cost of travel to Canadian Urological Association conferences.

INTRODUCTION: Canadian Urological Association (CUA) conferences are held annually across Canada. Guests from across the world attended, contributing to the overall carbon footprint of the conference with their travel and accommodations. This study identified the carbon footprint of each of the 2016 (Vancouver), 2018 (Halifax), and 2019 (Quebec City) CUA conferences to investigate their carbon footprint and help determine the most eco-friendly location to hold future conferences. METHODS: Registrant home institution was used to estimate the distance and method of transportation of attendee travel. Carbon footprint was calculated using an online calculator in tons of CO2 equivalents (tCO2). Total attendees, number of attendees driving, number of attendees flying, mean distance travelled per attendee, total carbon footprint, and average carbon footprint per attendee were calculated for each conference. Mean carbon footprint, and mean distance travelled were compared using a Brown-Forsythe ANOVA test, with Dunnett's T3 multiple comparisons test (α=0.05). RESULTS: Vancouver had the largest number of attendees (n=473; 407 flying, 66 driving), followed by Halifax (n=382; 331 flying, 51 driving), and Quebec City (n=362; 265 flying, 97 driving). The mean distance attendees travelled was greatest for the Vancouver CUA (6041 km/roundtrip) compared to Quebec City (3096 km/roundtrip, p<0.0001) and Halifax (2985 km/roundtrip, p<0.0001). There was no difference in mean distance travelled between Halifax and Quebec City (p=0.95). The highest total carbon footprint was seen in Vancouver (tCO2=447.76), followed by Quebec City (tCO2=217.04) and Halifax (tCO2=182.22). The average footprint per attendee was significantly higher in Vancouver (mean tCO2=1.08) compared to both Quebec City (mean tCO2=0.62, p<0.0001) and Halifax (mean tCO2=0.52, p<0.0001). There was no difference in the average footprint between Halifax and Quebec City (p=0.63). CONCLUSIONS: The estimated emissions associated with the Vancouver CUA conference is greater than both the Halifax and Quebec City locations combined. In-person conferences provide several benefits to the urological community. Incorporating environmental considerations into conference planning, such as conference location, could reduce the CUA conference's overall carbon footprint, mitigating the contribution to rising temperatures and negative health outcomes.