Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer.

Background: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. Objectives: We quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. Methods: A retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. Results: Black race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. Conclusions: Black patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.

Considerations for legal, ethical, and effective practice in dementia research.

Dementia represents a potentially overwhelming health burden, both for the UK and worldwide. Addressing this fast-growing issue is a key priority for the government, health service and the public. Advances in care including the development of efficacious disease-modifying, and eventually curative, treatments can only be achieved through effective dementia research. Specifically, research directly involving participants with dementia is essential to further understanding. However, working with cognitively impaired participants with and without capacity to consent to research presents unique ethical and legal challenges. For clinicians and scientists on the frontline of dementia research, scenarios frequently arise that pose such challenges. A lack of guidance for a consistent approach in navigating these scenarios limits researchers' ability to proceed with confidence. This represents a threat to the rights and wishes of research participants as well as the field at large, as it may lead to studies being unnecessarily terminated or, worse, poor practice. In this article, we take a multiprofessional approach, informed by carer input, to these issues. We review the relevant ethical and legal literature relating to the conduct of non-interventional research studies in patients with dementia. This includes a thorough recap of the Mental Capacity Act (2005), which provides a legal framework in England and Wales for conducting research with participants who lack capacity to consent. We also discuss the important, but sometimes incomplete, role of research ethics committees in guiding researchers. We then present and discuss a series of case vignettes designed to highlight areas of incomplete coverage by existing governance. These vignettes describe theoretical scenarios informed by our own real-word experiences of encountering ethical issues when conducting dementia research. They include scenarios in which participants demonstrate varying degrees of understanding of the research they are involved in and ability to communicate their wishes and feelings. Building on these vignettes, we then provide a checklist for researchers to work through when presented with similar scenarios. This checklist covers the key ethical, legal and practical considerations that we have argued for. Taken together, this article can act as a guide, previously lacking in the literature, for colleagues in the field to enable much needed ethical, legal and effective research.

An antibody to IL-1 receptor 7 protects mice from LPS-induced tissue and systemic inflammation.

Introduction: Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation. Methods: We reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models. Results: We first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model. Discussion: Altogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19.

Multiple Protein Profiler 1.0 (MPP): A Webserver for Predicting and Visualizing Physiochemical Properties of Proteins at the Proteome Level.

Determining the physicochemical properties of a protein can reveal important insights in their structure, biological functions, stability, and interactions with other molecules. Although tools for computing properties of proteins already existed, we could not find a comprehensive tool that enables the calculations of multiple properties for multiple input proteins on the proteome level at once. Facing this limitation, we developed Multiple Protein Profiler (MPP) 1.0 as an integrated tool that allows the profiling of 12 individual properties of multiple proteins in a significant manner. MPP provides a tabular and graphic visualization of properties of multiple proteins. The tool is freely accessible at https://mproteinprofiler.microbiologyandimmunology.dal.ca/ .

Cathodoluminescence studies of the optical properties of a zincblende InGaN/GaN single quantum well.

Zincblende GaN has the potential to improve the efficiency of green- and amber-emitting nitride light emitting diodes due to the absence of internal polarisation fields. However, high densities of stacking faults are found in current zincblende GaN structures. This study presents a cathodoluminescence spectroscopy investigation into the low-temperature optical behaviour of a zincblende GaN/InGaN single quantum well structure. In panchromatic cathodoluminescence maps, stacking faults are observed as dark stripes, and are associated with non-radiative recombination centres. Furthermore, power dependent studies were performed to address whether the zincblende single quantum well exhibited a reduction in emission efficiency at higher carrier densities-the phenomenon known as efficiency droop. The single quantum well structure was observed to exhibit droop, and regions with high densities of stacking faults were seen to exacerbate this phenomenon. Overall, this study suggests that achieving efficient emission from zinc-blende GaN/InGaN quantum wells will require reduction in the stacking fault density.

Saturation genome editing of BAP1 functionally classifies somatic and germline variants.

Many variants that we inherit from our parents or acquire de novo or somatically are rare, limiting the precision with which we can associate them with disease. We performed exhaustive saturation genome editing (SGE) of BAP1, the disruption of which is linked to tumorigenesis and altered neurodevelopment. We experimentally characterized 18,108 unique variants, of which 6,196 were found to have abnormal functions, and then used these data to evaluate phenotypic associations in the UK Biobank. We also characterized variants in a large population-ascertained tumor collection, in cancer pedigrees and ClinVar, and explored the behavior of cancer-associated variants compared to that of variants linked to neurodevelopmental phenotypes. Our analyses demonstrated that disruptive germline BAP1 variants were significantly associated with higher circulating levels of the mitogen IGF-1, suggesting a possible pathological mechanism and therapeutic target. Furthermore, we built a variant classifier with >98% sensitivity and specificity and quantify evidence strengths to aid precision variant interpretation.

Misophonia reactions in the general population are correlated with strong emotional reactions to other everyday sensory-emotional experiences.

Misophonic experiences are common in the general population, and they may shed light on everyday emotional reactions to multi-modal stimuli. We performed an online study of a non-clinical sample to understand the extent to which adults who have misophonic reactions are generally reactive to a range of audio-visual emotion-inducing stimuli. We also hypothesized that musicality might be predictive of one's emotional reactions to these stimuli because music is an activity that involves strong connections between sensory processing and meaningful emotional experiences. Participants completed self-report scales of misophonia and musicality. They also watched videos meant to induce misophonia, autonomous sensory meridian response (ASMR) and musical chills, and were asked to click a button whenever they had any emotional reaction to the video. They also rated the emotional valence and arousal of each video. Reactions to misophonia videos were predicted by reactions to ASMR and chills videos, which could indicate that the frequency with which individuals experience emotional responses varies similarly across both negative and positive emotional contexts. Musicality scores were not correlated with measures of misophonia. These findings could reflect a general phenotype of stronger emotional reactivity to meaningful sensory inputs. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Outcomes of Arthroscopic Debridement of the First Carpometacarpal Joint: A Systematic Review.

Background: Arthroscopic debridement is increasingly being utilised in patients with early-stage first carpometacarpal joint (FCMCJ) arthritis but has limited supportive evidence. This systematic review evaluates the literature, and reports on outcomes and adverse events following this procedure. Methods: An electronic literature search of PubMed, Embase, Medline and Cochrane Central, looking for studies describing outcomes following arthroscopic debridement in FCMCJ arthritis, was performed in November 2022. Studies where bony resection or interposition was performed as adjuncts were excluded. Reported outcomes included visual analogue scores (VAS) for pain; Disabilities of Arm, Shoulder and Hand (DASH) scores; pinch and grip strength; complications and re-operations. Results: Out of a total of 90 studies revealed from the search, only two studies were eligible for inclusion, with a cohort of 34 patients. Following arthroscopic debridement for FCMCJ osteoarthritis, the mean VAS improved by four units, mean DASH by 22 points, grip strength by 4.5 kg and pinch strength by 2 kg at mean follow-up of 18 months. The pooled complication and re-operation rates were 8.8% and 23.5%, respectively. Conclusions: There is a lack of evidence supporting the utility of FCMCJ arthroscopy and debridement in the management of patients with early arthritis. Although the limited evidence suggests that there may be some therapeutic benefit, further large-scale prospective studies need to be performed before making conclusive recommendations. Level of Evidence: Level III (Therapeutic).

Primary hyperoxaluria: Long-term outcomes of isolated kidney versus simultaneous liver/kidney transplant.

OBJECTIVES: To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH). METHODS: The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models. RESULTS: We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness. CONCLUSIONS: Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.

Expression of camelid-derived, single-domain antibodies (V H Hs) within the cytoplasm of mammalian cells as "intrabodies" has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined V H Hs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site. Resistance to RT conferred by the biparatopic V H H construct far exceeded that of either of the V H Hs alone and effectively inhibited all measurable RT-induced cytotoxicty in vitro . We propose that targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu.

Key features of chronic kidney disease (CKD) include tubulointerstitial inflammation and fibrosis. Protease activated receptor-2 (PAR2), a G-protein coupled receptor (GPCR) expressed by the kidney proximal tubular cells, induces potent proinflammatory responses in these cells. The hypothesis tested here was that PAR2 signalling can contribute to both inflammation and fibrosis in the kidney by transactivating known disease associated pathways. Using a primary cell culture model of human kidney tubular epithelial cells (HTEC), PAR2 activation induced a concentration dependent, PAR2 antagonist sensitive, secretion of TNF, CSF2, MMP-9, PAI-1 and CTGF. Transcription factors activated by the PAR2 agonist 2F, including NFκB, AP1 and Smad2, were critical for production of these cytokines. A TGF-ß receptor-1 (TGF-ßRI) kinase inhibitor, SB431542, and an EGFR kinase inhibitor, AG1478, ameliorated 2F induced secretion of TNF, CSF2, MMP-9, and PAI-1. Whilst an EGFR blocking antibody, cetuximab, blocked PAR2 induced EGFR and ERK phosphorylation, a TGF-ßRII blocking antibody failed to influence PAR2 induced secretion of PAI-1. Notably simultaneous activation of TGF-ßRII (TGF-ß1) and PAR2 (2F) synergistically enhanced secretion of TNF (2.2-fold), CSF2 (4.4-fold), MMP-9 (15-fold), and PAI-1 (2.5-fold). In summary PAR2 activates critical inflammatory and fibrotic signalling pathways in human kidney tubular epithelial cells. Biased antagonists of PAR2 should be explored as a potential therapy for CKD.

Bee monitoring by community scientists: comparing a collections-based program with iNaturalist.

Bee monitoring, or widespread efforts to document bee community biodiversity, can involve data collection using lethal (specimen collections) or non-lethal methods (observations, photographs). Additionally, data can be collected by professional scientists or by volunteer participants from the general public. Collection-based methods presumably produce more reliable data with fewer biases against certain taxa, while photography-based approaches, such as data collected from public natural history platforms like iNaturalist, can involve more people and cover a broader geographic area. Few efforts have been made to quantify the pros and cons of these different approaches. We established a community science monitoring program to assess bee biodiversity across the state of Pennsylvania (USA) using specimen collections with nets, blue vane traps, and bowl traps. We recruited 26 participants, mostly Master Gardeners, from across the state to sample bees after receiving extensive training on bee monitoring topics and methods. The specimens they collected were identified to species, stored in museum collections, and the data added to public databases. Then, we compared the results from our collections to research-grade observations from iNaturalist during the same time period (2021 and 2022). At state and county levels, we found collections data documented over twice as much biodiversity and novel baseline natural history data (state and county records) than data from iNaturalist. iNaturalist data showed strong biases toward large-bodied and non-native species. This study demonstrates the value of highly trained community scientists for collections-based research that aims to document patterns of bee biodiversity over space and time.

Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome.

Endothelial cells (ECs) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. Pulmonary endothelial barrier integrity is maintained through coordinated cellular processes involving receptors, signaling molecules, junctional complexes, and protein-regulated cytoskeletal reorganization. In acute lung injury (ALI) or its more severe form acute respiratory distress syndrome (ARDS), the loss of endothelial barrier integrity secondary to endothelial dysfunction caused by severe pulmonary inflammation and/or infection leads to pulmonary edema and hypoxemia. Pro-inflammatory agonists such as histamine, thrombin, bradykinin, interleukin 1ß, tumor necrosis factor α, vascular endothelial growth factor, angiopoietin-2, and platelet-activating factor, as well as bacterial toxins and reactive oxygen species, cause dynamic changes in cytoskeletal structure, adherens junction disorganization, and detachment of vascular endothelial cadherin (VE-cadherin) from the actin cytoskeleton, leading to an increase in endothelial permeability. Endothelial interactions with leukocytes, platelets, and coagulation enhance the inflammatory response. Moreover, inflammatory infiltration and the associated generation of pro-inflammatory cytokines during infection cause EC death, resulting in further compromise of the structural integrity of lung endothelial barrier. Despite the use of potent antibiotics and aggressive intensive care support, the mortality of ALI is still high, because the mechanisms of pulmonary EC barrier disruption are not fully understood. In this review, we summarized recent advances in the studies of endothelial cytoskeletal reorganization, inter-endothelial junctions, endothelial inflammation, EC death, and endothelial repair in ALI and ARDS, intending to shed some light on the potential diagnostic and therapeutic targets in the clinical management of the disease.

De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals where it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologs. Using RNA-sequencing, we show how 5' splice site usage is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 bp region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

The impact of metabolic syndrome on short term radical cystectomy complications.

PURPOSE: Radical cystectomy is a highly morbid procedure with short term perioperative complications rates cited to be as high as 60%. Short term perioperative complications have been demonstrated to be more frequent in underweight and overweight patients. We sought to evaluate the impact of metabolic syndrome on surgical outcomes. MATERIALS AND METHODS: We identified 19,071 eligible patients who underwent radical cystectomy for nonmetastatic bladder cancer using the American College of Surgeons National Surgical Quality Improvement Program database between the years 2014 to 2021. The primary exposure was the presence of metabolic syndrome (body mass index >30, hypertension, diabetes) and included 1,566 patients. Our primary outcome was the development of a post operative surgical complication with secondary outcomes of the impact on length of stay, return to operating room, readmission, and 30 day mortality. RESULTS: Metabolic syndrome was associated with an increased rate of complications following radical cystectomy (P < 0.001). Complications were demonstrated in 68% of patients with metabolic syndrome in comparison to 60% of those without. Following multivariable adjustment for relevant demographic, comorbidity, and treatment factors, compared to patients without metabolic syndrome, patients with metabolic syndrome were significantly more likely to experience a complication in the 30 days following cystectomy. Among the secondary outcomes, on multivariable analysis significant differences were found in the risk of readmission and extended length of stay. Critically, the risk of 30 day morbidity was associated with a 1.8 fold increase in those with metabolic syndrome. CONCLUSIONS: Metabolic syndrome demonstrates significantly worse perioperative outcomes following radical cystectomy for bladder cancer.

Need for strategic communications and stakeholder engagement to advance acceptability of an overdose preventing vaccine targeting fentanyl.

BACKGROUND: Fentanyl is a synthetic opioid, exposure to which has led to hundreds of thousands of overdose deaths. Novel vaccines are being developed that might protect against fentanyl overdose. Proactive attention to strategic communications and stakeholder engagement may smooth uptake of a novel vaccine given known challenges around vaccine hesitancy and concern for stigma related to substance use. METHODS: Qualitative interviews (N = 74) with a purposive sample of adolescents/young adults with opioid use disorder (OUD), family members of persons with OUD, experts in substance use treatment and harm reduction, and community members were conducted and thematically analyzed to discern attitudes toward a fentanyl vaccine, and directions for communications and engagement. RESULTS: Major themes reflected personal concerns for biomedical risk and system-level concerns for alignment and integration of an overdose preventing vaccine with prevailing beliefs about addiction and associated frameworks and philosophies for treatment and response. CONCLUSION: Acceptability and implementation of a novel fentanyl vaccine targeting overdose will need precision communications that address biomedical, moral/spiritual, and structural perspectives about the nature of addiction. Education about the purpose and limits of a fentanyl vaccine, partnerships with diverse stakeholders from throughout the opioid response ecosystem and interweaving of a vaccine strategy into comprehensive prevention and treatment are recommended.

Activation of AMPD2 drives metabolic dysregulation and liver disease in mice with hereditary fructose intolerance.

Hereditary fructose intolerance (HFI) is a painful and potentially lethal genetic disease caused by a mutation in aldolase B resulting in accumulation of fructose-1-phosphate (F1P). No cure exists for HFI and treatment is limited to avoid exposure to fructose and sugar. Using aldolase B deficient mice, here we identify a yet unrecognized metabolic event activated in HFI and associated with the progression of the disease. Besides the accumulation of F1P, here we show that the activation of the purine degradation pathway is a common feature in aldolase B deficient mice exposed to fructose. The purine degradation pathway is a metabolic route initiated by adenosine monophosphate deaminase 2 (AMPD2) that regulates overall energy balance. We demonstrate that very low amounts of fructose are sufficient to activate AMPD2 in these mice via a phosphate trap. While blocking AMPD2 do not impact F1P accumulation and the risk of hypoglycemia, its deletion in hepatocytes markedly improves the metabolic dysregulation induced by fructose and corrects fat and glycogen storage while significantly increasing the voluntary tolerance of these mice to fructose. In summary, we provide evidence for a critical pathway activated in HFI that could be targeted to improve the metabolic consequences associated with fructose consumption.

Targeted mapping and utilization of the perihepatic surface for therapeutic beta cell replacement and retrieval in diabetic non-human primates.

Introduction: Successful diabetes reversal using pancreatic islet transplantation by various groups illustrates the significant achievements made in cell-based diabetes therapy. While clinically, intraportal islet delivery is almost exclusively used, it is not without obstacles, including instant blood-mediated inflammatory reaction (IBMIR), relative hypoxia, and loss of function over time, therefore hindering long-term success. Here we demonstrate the perihepatic surface of non-human primates (NHPs) as a potential islet delivery site maximizing favorable characteristics, including proximity to a dense vascular network for adequate oxygenation while avoiding IBMIR exposure, maintenance of portal insulin delivery, and relative ease of accessibility through minimally invasive surgery or percutaneous means. In addition, we demonstrate a targeted mapping technique of the perihepatic surface, allowing for the testing of multiple experimental conditions, including a semi-synthetic hydrogel as a possible three-dimensional framework to improve islet viability. Methods: Perihepatic allo-islet cell transplants were performed in immunosuppressed cynomolgus macaques using a targeted mapping technique to test multiple conditions for biocompatibility. Transplant conditions included islets or carriers (including hydrogel, autologous plasma, and media) alone or in various combinations. Necropsy was performed at day 30, and histopathology was performed to assess biocompatibility, immune response, and islet viability. Subsequently, single-injection perihepatic allo-islet transplant was performed in immunosuppressed diabetic cynomolgus macaques. Metabolic assessments were measured frequently (i.e., blood glucose, insulin, C-peptide) until final graft retrieval for histopathology. Results: Targeted mapping biocompatibility studies demonstrated mild inflammatory changes with islet-plasma constructs; however, significant inflammatory cell infiltration and fibrosis were seen surrounding sites with the hydrogel carrier affecting islet viability. In diabetic NHPs, perihepatic islet transplant using an autologous plasma carrier demonstrated prolonged function up to 6 months with improvements in blood glucose, exogenous insulin requirements, and HbA1c. Histopathology of these islets was associated with mild peri-islet mononuclear cell infiltration without evidence of rejection. Discussion: The perihepatic surface serves as a viable site for islet cell transplantation demonstrating sustained islet function through 6 months. The targeted mapping approach allows for the testing of multiple conditions simultaneously to evaluate immune response to biomaterials at this site. Compared to traditional intraportal injection, the perihepatic site is a minimally invasive approach that allows the possibility for graft recovery and avoids IBMIR.