An intranasally delivered ultra-conserved siRNA prophylactically represses SARS-CoV-2 infection in the lung and nasal cavity.

There remains a striking overall mortality burden of COVID-19 worldwide. Given the waning effectiveness of current SARS-CoV-2 antivirals due to the rapid emergence of new variants of concern (VOC), we employed a direct-acting molecular therapy approach using gene silencing RNA interference (RNAi) technology. In this study, we developed and screened several ultra-conserved small-interfering RNAs (siRNAs) before selecting one potent siRNA candidate for pre-clinical in vivo testing. This non-immunostimulatory, anti-SARS-CoV-2 siRNA candidate maintains its antiviral activity against all tested SARS-CoV-2 VOC and works effectively as a single agent. For the first time, significant antiviral effects in both the lungs and nasal cavities of SARS-CoV-2 infected mice were observed when this siRNA candidate was delivered intranasally (IN) as a prophylactic agent with the aid of lipid nanoparticles (LNPs). Importantly, a pre-exposure prophylactic IN-delivered anti-SARS-CoV-2 siRNA antiviral that can ameliorate viral replication in the nasal cavity could potentially prevent aerosol spread of respiratory viruses. An IN delivery approach would allow for the development of a direct-acting nasal spray approach that could be self-administered prophylactically.

Epidemiological transition: a historical analysis of immigration patterns by country of origin (1861-1986) related to circulatory system diseases and all-cause mortality in twentieth-century Australia.

BACKGROUND AND OBJECTIVES: Circulatory system disease (CSD) patterns vary over time and between countries, related to lifestyle risk factors, associated in turn with socioeconomic circumstances. Current global CSD epidemics in developing economies are similar in scale to those observed previously in the USA and Australasia. Australia exhibits an important macroeconomic phenomenon as a rapidly transitioning economy with high immigration throughout the nineteenth and twentieth centuries. We wished to examine how that historical immigration related to CSD patterns subsequently. METHODS AND SETTING: We provide a novel empirical analysis employing census-derived place of birth by age bracket and sex from 1891 to 1986, in order to map patterns of immigration against CSD mortality rates from 1907 onwards. Age-specific generalised additive models for both CSD mortality in the general population, and all-cause mortality for the foreign-born (FB) only, from 1910 to 1980 were also devised for both males and females. RESULTS: The percentage of FB fell from 32% in 1891 to 9.8% in 1947. Rates of CSD rose consistently, particularly from the 1940s onwards, peaked in the 1960s, then declined sharply in the 1980s and showed a strong period effect across age groups and genders. The main effects of age and census year and their interaction were highly statistically significant for CSD mortality for males (p<0.001, each term) and for females (p<0.001, each term). The main effect of age and year were statistically significant for all-cause mortality minus net migration rates for the FB females (each p<0.001), and for FB males, age (p<0.001) was significant. CONCLUSIONS: We argue our empirical calculations, supported by historical and socioepidemiological evidence, employing immigration patterns as a proxy for epidemiological transition, affirm the life course hypothesis that both early life circumstances and later life lifestyle drive CSD patterns.

Prophylactic intranasal administration of lipid nanoparticle formulated siRNAs reduce SARS-CoV-2 and RSV lung infection.

RNA interference (RNAi) is an emerging and promising therapy for a wide range of respiratory viral infections. This highly specific suppression can be achieved by the introduction of short-interfering RNA (siRNA) into mammalian systems, resulting in the effective reduction of viral load. Unfortunately, this has been hindered by the lack of a good delivery system, especially via the intranasal (IN) route. Here, we have developed an IN siRNA encapsulated lipid nanoparticle (LNP) in vivo delivery system that is highly efficient at targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) lung infection in vivo. Importantly, IN siRNA delivery without the aid of LNPs abolishes anti-SARS-CoV-2 activity in vivo. Our approach using LNPs as the delivery vehicle overcomes the significant barriers seen with IN delivery of siRNA therapeutics and is a significant advancement in our ability to delivery siRNAs. The study presented here demonstrates an attractive alternate delivery strategy for the prophylactic treatment of both future and emerging respiratory viral diseases.

Assessing the outcomes of parasacral transcutaneous electrical nerve stimulation (PTENS) in the treatment of enuresis in children: A systematic review and meta-analysis of randomized control trials.

INTRODUCTION: Nocturnal enuresis (NE) is a common pathology in children that can have significant behavioral, emotional, and social impacts on a child's life. Recent studies have assessed PTENS as a potential treatment method for NE, particularly in those who do not respond to initial first-line treatments. Literature has shown varying results with regard to its success. There has been no systematic review and meta-analysis to date assessing outcomes following this treatment. OBJECTIVES: Despite multiple studies showing the potential benefits of PTENS in NE, there has been no consensus regarding its efficacy. The aim of this study was to systematically analyze the effects of PTENS on children with NE. STUDY DESIGN: In September 2021, a search of PubMed, Embase and the Cochrane Library was carried out for studies relating to outcomes following PTENS in children with NE. Studies included were original publication English language randomized controlled trial (RCT's) with at least ten children receiving parasacral transcutaneous electrical nerve stimulation (PTENS). After assessing for relevant studies, data were collated and analyzed from the included studies. Risk of bias was assessed using the Cochrane seven domain assessment. Our primary outcome was response and nonresponse to treatment. These results were combined in a fixed effects meta-analysis model to obtain an overall estimate of the success rate. Information regarding demographics was also collected. There was no external funding for this review. RESULTS: Of 145 studies found initially, four RCT's (208 children) were included. The weighted mean rate of full response to active PTENS was 10.8% (0%-19%). All studies considered, meta-analysis showed no difference between PTENS and controls (RR: 0.70, 95% confidence interval [CI: 0.37-1.32]). Subgroup analysis of monosymptomatic enuresis showed no effect of PTENS compared to controls (RR = 0.58, 95% CI: [0.24-1.42]). When grouped, studies comparing PTENS to sham/behavioral treatment showed no benefit compared to controls (RR = 0.81, 95% CI: [0.05-12.53]) and those comparing PTENS to biofeedback/interferential current (IFC) showed no difference to controls (RR = 0.69, 95% CI: [0.36-1.33]). There was no evidence of a difference between cases and controls between these latter subgroups (RR = 0.70, 95% CI: [0.37-1.32]). DISCUSSION/CONCLUSION: Our results suggest that PTENS has no clear benefit in the management of children with NE compared to controls. Subgroup analysis showed that its use in monosymptomatic NE has no clear advantage. However, this review has highlighted the need for further high quality studies. Limitations to this review included a relatively small sample size and the use of prior or concomitant therapies.

Prepubertal methylphenidate leads to sex-dependent differences in probabilistic discounting.

Prescription psychostimulants, such as methylphenidate (MPH), have served as a first line treatment for ADHD and associated developmental disorders since 1961. Psychostimulants has been shown to improve attention, response inhibition, and reduce hyperactivity in patients with ADHD, as well as in non-clinical human populations and animals. While there is a considerable amount of preclinical research investigating the effects of stimulant medications on reward sensitivity and basic learning in male rats, less is understood about their effects in females. Further, there are competing theories on the long-term cognitive impact of MPH, specifically in children who do not have ADHD. To this end, Long-Evans female and male rats were exposed to methylphenidate (0, 2.5, 5 mg/kg, BID, IP) for 20 days during early development (PD10-29). After discontinuation of MPH into adulthood, rats (beginning PD 60) were trained and tested for risk-preference using a 2-choice probabilistic discounting task. For this task, rats were given an option between a 'large-risky' choice (3 sugar pellets delivered on a probabilistic VR schedule) and 'small-certain' choice (1 sugar pellet delivered on a FR schedule). Rats were subsequently tested on an open field conflict test. The results demonstrate that prepubertal exposure to MPH can have lasting effects on decision-making. Specifically, female rats treated with 2.5 mg/kg MPH displayed a decrease in preference for the risky option, whereas male rats treated with the same dose showed an overall increase in preference compared to sex-matched controls. Irrespective of sex, rats treated with 2.5 mg/kg MPH also demonstrated a decrease in anxiety/inhibitory behavior on the modified open field test compared to controls. These results were not due to differences in locomotor behavior. Overall, the study contributes to the growing body of evidence to suggest that MPH exposure early in development can have a sex-dependent impact on decision-making in adulthood.

Engineered extracellular vesicles directed to the spike protein inhibit SARS-CoV-2.

SARS-CoV-2 (CoV-2) viral infection results in COVID-19 disease, which has caused significant morbidity and mortality worldwide. A vaccine is crucial to curtail the spread of SARS-CoV-2, while therapeutics will be required to treat ongoing and reemerging infections of SARS-CoV-2 and COVID-19 disease. There are currently no commercially available effective anti-viral therapies for COVID-19, urging the development of novel modalities. Here, we describe a molecular therapy specifically targeted to neutralize SARS-CoV-2, which consists of extracellular vesicles (EVs) containing a novel fusion tetraspanin protein, CD63, embedded within an anti-CoV-2 nanobody. These anti-CoV-2-enriched EVs bind SARS-CoV-2 spike protein at the receptor-binding domain (RBD) site and can functionally neutralize SARS-CoV-2. This work demonstrates an innovative EV-targeting platform that can be employed to target and inhibit the early stages of SARS-CoV-2 infection.

A multinational survey on the management of the urinary tract in newborns with spina bifida: Are we following current EAU/ESPU guidelines?

AIMS: In August 2019, the European Association of Urology (EAU) and European Society for Paediatric Urology (ESPU) published updated guidelines on the management of neurogenic bladder in children and adolescents. Our study aimed to establish whether members of the ESPU are adhering to these guidelines. METHODS: We designed a survey comprising 26 questions using SurveyMonkey®. Respondents were asked about management of neurogenic bladder at birth in newborns with spina bifida (SB), urological investigations, as well as short and long-term follow-up in their institutions. RESULTS: There were 103 respondents to the survey (754 recipients, giving a response rate of 14%) spanning 36 countries. 100% of respondents carry out a renal/bladder ultrasound at birth. Only 53% routinely commence clean intermittent catheterization soon after birth as recommended by the guidelines. Only 56% recommend anticholinergic medications after abnormal videourodynamics (VUDs). The guidelines recommend the use of continued antibiotic prophylaxis if there is evidence of vesicoureteral reflux and hostile bladder/non-conclusive results on VUDs which is followed by only 30% of providers. 63% of respondents carry out baseline VUDs at the recommended time. Seeing larger volumes of SB patients, having a formal SB protocol, having formal SB multidisciplinary clinics and working in a tertiary referral center did not make respondents more likely to adhere to guidelines. CONCLUSIONS: Our survey demonstrated that large variations from the EAU/ESPU guidelines exist in practice. The study confirms that further work is required across institutions and countries to implement these evidence-based recommendations for standardized practice.

Intraoperative autologous transfusion and oncologic outcomes in liver transplantation for hepatocellular carcinoma: a propensity matched analysis.

BACKGROUND: Intraoperative autologous transfusion (IAT) of salvaged blood is a common method of resuscitation during liver transplantation (LT), however concern for recurrence in recipients with hepatocellular carcinoma (HCC) has limited widespread adoption. METHODS: A review of patients undergoing LT for HCC between 2008 and 2018 was performed. Clinicopathologic and intraoperative characteristics associated with inferior recurrence-free (RFS) and overall survival (OS) were identified using Kaplan-Meier analysis and uni-/multi-variable Cox proportional hazards modeling. Propensity matching was utilized to derive clinicopathologically similar groups for subgroup analysis. RESULTS: One-hundred-eighty-six patients were identified with a median follow up of 65 months. Transplant recipients receiving IAT (n = 131, 70%) also had higher allogenic transfusions (median 5 versus 0 units, P < 0.001). There were 14 recurrences and 46 deaths, yielding an estimated 10-year RFS and OS of 89% and 67%, respectively. IAT was not associated with RFS (HR 0.89/liter, P = 0.60), or OS (HR 0.98/liter, P = 0.83) pre-matching, or with RFS (HR 0.97/liter, P = 0.92) or OS (HR 1.04/liter, P = 0.77) in the matched cohort (n = 49 per group). CONCLUSION: IAT during LT for HCC is not associated with adverse oncologic outcomes. Use of IAT should be encouraged to minimize the volume of allogenic transfusion in patients undergoing LT for HCC.

Complete protection by a single-dose skin patch-delivered SARS-CoV-2 spike vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 160 million people and resulted in more than 3.3 million deaths, and despite the availability of multiple vaccines, the world still faces many challenges with their rollout. Here, we use the high-density microarray patch (HD-MAP) to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin. We show that the vaccine is thermostable on the patches, with patch delivery enhancing both cellular and antibody immune responses. Elicited antibodies potently neutralize clinically relevant isolates including the Alpha and Beta variants. Last, a single dose of HD-MAP­delivered spike provided complete protection from a lethal virus challenge in an ACE2-transgenic mouse model. Collectively, these data show that HD-MAP delivery of a SARS-CoV-2 vaccine was superior to traditional needle-and-syringe vaccination and may be a significant addition to the ongoing COVID-19 (coronavirus disease 2019) pandemic.

Covid-19, non-Covid-19 and excess mortality rates not comparable across countries.

Evidence that more people in some countries and fewer in others are dying because of the pandemic, than is reflected by reported coronavirus disease 2019 (Covid-19) mortality rates, is derived from mortality data. Using publicly available databases, deaths attributed to Covid-19 in 2020 and all deaths for the years 2015-2020 were tabulated for 35 countries together with economic, health, demographic and government response stringency index variables. Residual mortality rates (RMR) in 2020 were calculated as excess mortality minus reported mortality rates due to Covid-19 where excess deaths were observed deaths in 2020 minus the average for 2015-2019. Differences in RMR are differences not attributed to reported Covid-19. For about half the countries, RMR's were negative and for half, positive. The absolute rates in some countries were double those in others. In a regression analysis, population density and proportion of female smokers were positively associated with both Covid-19 and excess mortality while the human development index and proportion of male smokers were negatively associated with both. RMR was not associated with any of the investigated variables. The results show that published data on mortality from Covid-19 cannot be directly comparable across countries. This may be due to differences in Covid-19 death reporting and in addition, the unprecedented public health measures implemented to control the pandemic may have produced either increased or reduced excess deaths due to other diseases. Further data on cause-specific mortality is required to determine the extent to which residual mortality represents non-Covid-19 deaths and to explain differences between countries.

The need to incorporate the impact of population ageing into the post-COVID-19 policy and planning reset in Low and Middle Income Countries.

The COVID-19 pandemic is likely to widen the health care demand-supply gap, especially in low- and middle-income countries (LMICs). The virus has had the greatest impact on older persons in terms of morbidity and mortality, and is occurring at a time of rapid population ageing, which is happening three times faster in LMICs than in high-income countries. Addressing the demand-supply gap in a post-COVID-19 era, in which resources are further constrained, will require a major 'reset' of the health system. In this article, we argue that the impact of ageing populations needs to be factored into the post-COVID-19 policy and planning reset including explicit, transparent prioritisation processes.

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective small interfering RNA (siRNA) therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle (LNP) delivery system. Multiple siRNAs targeting highly conserved regions of the SARS-CoV-2 virus were screened, and three candidate siRNAs emerged that effectively inhibit the virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel LNP formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three candidate siRNAs emerged that effectively inhibit virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel lipid nanoparticle formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.

IFN-γ Critically Enables the Intratumoural Infiltration of CXCR3+ CD8+ T Cells to Drive Squamous Cell Carcinoma Regression.

Ultraviolet (UV) radiation-induced tumours carry a high mutational load, are highly immunogenic, and often fail to grow when transplanted into normal, syngeneic mice. The aim of this study was to investigate factors critical for the immune-mediated rejection of cutaneous squamous cell carcinoma (SCC). In our rejection model, transplanted SCC establish and grow in mice immunosuppressed with tacrolimus. When tacrolimus is withdrawn, established SCC tumours subsequently undergo immune-mediated tumour rejection. Through the depletion of individual immune subsets at the time of tacrolimus withdrawal, we established a critical role for CD8+ T cells, but not CD4+ T cells, γδ T cells, or NK cells, in driving the regression of SCC. Regression was critically dependent on IFN-γ, although IFN-γ was not directly cytotoxic to SCC cells. IFN-γ-neutralisation abrogated SCC regression, significantly reduced CD8+ T cell-infiltration into SCC, and significantly impaired the secretion of CXCL9, CXCL10 and CCL5 within the tumour microenvironment. A strong positive correlation was revealed between CXCL10 expression and CD8+ T cell abundance in tumours. Indeed, blockade of the CXCL10 receptor CXCR3 at the time of tacrolimus withdrawal prevented CD8+ T cell infiltration and the regression of SCC. Chimeric models revealed an important role for immune cells as producers of IFN-γ, but not as recipients of IFN-γ signals via the IFN-γ receptor. Together, these findings suggest a key role for IFN-γ in driving the expression of chemokines within the tumour environment essential for the destruction of established SCC by CD8+ T cells.

Co-Creating Descriptors and a Definition for Person-Centred Coordinated Health Care: An Action Research Study.

The aim of this study was to co-create a definition and generic descriptors for person-centred coordinated care for Ireland generated from service users' narratives. An overarching action research approach was used to engage and empower people to tangibly impact health policy and practice. Through focus groups and a qualitative survey, primary data were collected from a national sample of health services users, caregivers and health care service users' representative groups. Thematic analysis was used to analyse the data. Three major themes were co-produced as essential care elements. These were: 'My experience of healthcare', 'Care that I am confident in' and 'My journey through healthcare'. Through an IPPOSI partner project steering group and their membership groups' contribution, these themes were further refined into a definition of person-centred coordinated care and nineteen related generic descriptors. Key findings demonstrate that within complex, fragmented healthcare systems, the subjective expectations of service users should be integrated into care delivery, with a scaffolding of services to meet service users' needs between care settings and disciplines and over time.

Comparing the outcomes of parasacral transcutaneous electrical nerve stimulation for the treatment of lower urinary tract dysfunction in children: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Despite published evidence in recent decades suggesting improvement in lower urinary tract symptoms (LUTS) with the use of parasacral transcutaneous electrical nerve stimulation (PTENS), no consensus guidelines for therapy exist. This study systematically reviews the literature to assess the effect of PTENS in children with LUTS. METHODS: A database search conducted up to December 2019 included Medline, EMBASE, and the Cochrane Library. From the literature review, 6 randomized controlled studies (234 participants) comparing PTENS and standard treatment (urotherapy/anticholinergics) were considered. From each study, the success rates were available for PTENS and the control group. The ratio of success rates was computed-that is, the risk ratio (RR) and the risk difference (RD). RESULTS: The overall success rate with PTENS was 1.92 times that of children undergoing standard urotherapy alone (RR: 1.92, 95% confidence interval [CI: 1.02, 3.61]) and 1.56 for those undergoing either urotherapy alone or with pharmacotherapy (anticholinergics; RR: 1.56, 95% CI [1.04, 2.40]). No difference in the success rate was found when PTENS was used in patients failing previous treatment (urotherapy and pharmacological therapy; RR: 0.175, 95% CI [0.02, 1.45]). CONCLUSIONS: Current evidence suggests that PTENS is beneficial in children with LUTS. The chance of success is 1.92 times that of children undergoing standard urotherapy. However, in children who have failed urotherapy and pharmacological therapy, PTENS monotherapy has a limited role and should be an adjunct. Literature shortcomings included small numbers of patients, differing inclusion criteria, and PTENS protocols. A need exists for quality multicenter randomized controlled trials to prove the efficacy of PTENS in children with LUTS.

Comparative Analysis of Swept-Source Optical Coherence Tomography and Partial Coherence Interferometry Biometers in the Prediction of Cataract Surgery Refractive Outcomes.

PURPOSE: To compare the accuracy of pre-operative corneal measurements obtained with four devices, and the refractive outcomes of two optical biometers. SETTING: Private practice. DESIGN: Retrospective. METHODS: Data taken from biometric measurements on 299 consecutive eyes prior to cataract surgery were retrospectively analyzed using the Argos SS-Optical Biometer and the Lenstar LS900 PCI optical biometer. As part of the standard cataract surgery pre-operative exam, patients also underwent placido disk topography and Scheimpflug tomography. Keratometry, anterior chamber depth, corneal diameter, pupil diameter, central corneal thickness and axial length were all measured. The comparable measurements were compared. Finally, for those eyes where cataract surgery was performed, the post-operative refractive results were compared to the predictive results of the two biometers. RESULTS: The SS-OCT Argos was able to measure all eyes, while five eyes could not be measured with the Lenstar LS900 PCI. Axial length measurements were performed only with the Argos and Lenstar devices. The eyes that could not be measured by the Lenstar LS900 PCI included dense grade IV nuclear sclerosis and large posterior subcapsular cataracts. In the primary endpoints, there was strong correlation between the Argos and the Lenstar devices in eyes with an axial length between 20 and 30 mm. CONCLUSION: The predictive accuracies of the Argos Optical Biometer and Lenstar LS900 PCI are similar, except in medium and long eyes, in which the predictive accuracy of Argos SS-OCT biometry was higher. The Argos system was found easier to use by technicians when compared to the other biometry devices.

CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells.

The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8+ TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226hi TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226+CD8+ T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226.

Force Distribution in the Canine Proximal Radio-Ulnar Joint on Extension of the Carpal Joint: A Cadaveric Study.

OBJECTIVE: The aim of this study was to measure the load on the lateral and medial aspects of the proximal radio-ulnar joint during extension of the carpus. STUDY DESIGN: This was an ex vivo biomechanical study. SAMPLE POPULATION: Twenty-two cadaveric Greyhound thoracic limbs were used. METHODS: Twenty-two paired thoracic limbs were used. The olecranon was attached to a custom jig with the foot resting on a stationary anvil. Load sensors were inserted into the proximal radio-ulnar joint, between the radial head and the lateral coronoid process, and between the radial head and the medial coronoid process. Specimens were tested under compression with measurements taken at 0, 4, 9 and 13.5 mm of axial displacement. Data collected at each point included forces on the specimen and medial and lateral coronoid processes as well as the angle of carpal joint extension. RESULTS: A linear mixed effects model relating load on the specimen and carpal joint extension angle had an R-squared value of 0.66, and load at the level of the medial coronoid process and angle of carpal extension had an R-squared value of 0.61. There was a significant difference in the loads measured on the lateral and medial coronoid processes at all angles (p < 0.0001). CONCLUSION: Extension of the carpus results in asymmetric loading of the proximal radio-ulnar joint. CLINICAL SIGNIFICANCE: The findings of this study show that loading of the medial coronoid process may be more complex than originally thought and supports the future investigation of novel management and therapeutic options for affected patients.