Cancer Incidence After Diagnosis of Abdominal Aortic Aneurysm-Brief Report.

BACKGROUND: Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic pathogenesis from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors. METHODS: All individuals ≥18 years of age with ≥36 months of continuous coverage between 2008 and 2020 were enrolled. Those with potential Mendelian etiologies of AAA, aortic aneurysm with nonspecific anatomic location, or a cancer diagnosis before the start of follow-up were excluded. A subgroup analysis was performed of individuals having the Health Risk Assessment records including tobacco use and body mass index. The following groups of individuals were compared: (1) with AAA, (2) with non-AAA CVD, and (3) without any CVD. RESULTS: The propensity score-matched cohort included 58 993 individuals with AAA, 117 986 with non-AAA CVD, and 58 993 without CVD. The 5-year cumulative incidence of cancer was 13.1% (12.8%-13.5%) in participants with AAA, 10.1% (9.9%-10.3%) in participants with non-AAA CVD, and 9.6% (9.3%-9.9%) in participants without CVD. Multivariable-adjusted Cox proportional hazards regression models found that patients with AAA exhibited a higher cancer risk than either those with non-AAA CVD (hazard ratio, 1.28 [95% CI, 1.23-1.32]; P<0.001) or those without CVD (hazard ratio, 1.32 [95% CI, 1.26-1.38]; P<0.001). Results remained consistent after excluding common smoking-related cancers and when adjusting for tobacco use and body mass index. CONCLUSIONS: Patients with AAA may have a unique risk of cancer requiring further mechanistic study and investigation of the role of enhanced cancer screening.

Role of vascular smooth muscle cell clonality in atherosclerosis.

Atherosclerotic cardiovascular disease remains the leading cause of death worldwide. While many cell types contribute to the growing atherosclerotic plaque, the vascular smooth muscle cell (SMC) is a major contributor due in part to its remarkable plasticity and ability to undergo phenotype switching in response to injury. SMCs can migrate into the fibrous cap, presumably stabilizing the plaque, or accumulate within the lesional core, possibly accelerating vascular inflammation. How SMCs expand and react to disease stimuli has been a controversial topic for many decades. While early studies relying on X-chromosome inactivation were inconclusive due to low resolution and sensitivity, recent advances in multi-color lineage tracing models have revitalized the concept that SMCs likely expand in an oligoclonal fashion during atherogenesis. Current efforts are focused on determining whether all SMCs have equal capacity for clonal expansion or if a "stem-like" progenitor cell may exist, and to understand how constituents of the clone decide which phenotype they will ultimately adopt as the disease progresses. Mechanistic studies are also beginning to dissect the processes which confer cells with their overall survival advantage, test whether these properties are attributable to intrinsic features of the expanding clone, and define the role of cross-talk between proliferating SMCs and other plaque constituents such as neighboring macrophages. In this review, we aim to summarize the historical perspectives on SMC clonality, highlight unanswered questions, and identify translational issues which may need to be considered as therapeutics directed against SMC clonality are developed as a novel approach to targeting atherosclerosis.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the NIRAPA signal, immunohistochemistry, spatial transcriptomics and spatial proteomics were co-registered with imaging and applied to adjacent plaque sections. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and with the cytoplasmic contents of inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque and a methodology for fusing molecular imaging with spatial transcriptomic and proteomic methods.

The emotionally exhausted treating the mentally unwell? A systematic review of burnout and stress interventions for psychologists.

Healthcare providers are at high risk of occupational burnout, which has negative implications on the individual, their profession, the organisation and their patients. Psychologists are particularly susceptible to the repercussions of burnout due to the emotionally draining nature and content of their work. However, research has failed to outline and evaluate effective interventions for burnout within the profession. This study aimed to investigate the treatment effectiveness of burnout through a systematic literature review. Systematic searches of four databases using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were conducted. A total of 4832 articles were identified, and 15 were included in the final analysis. The search was limited to scholarly and peer-reviewed journals published in the English language, which measured and utilised a form of intervention for the treatment of burnout or stress and included participants within the psychology profession. Interventions identified included mindfulness, training courses, self-care and other therapy-based forms of interventions. Approximately 60% of study participants reported moderate to high levels of stress. Interventions were largely variable in modality, frequency and duration of sessions and follow-up period. Of the 15 studies included within the review, only four measured burnout as an outcome variable, while the others measured stress. Findings of this systematic review indicate that mindfulness-based interventions may be a starting point for reducing stress; however, the most effective intervention for psychologists who have reached burnout is largely unclear. It is recommended that future studies focus on the identification and measurement of burnout, are more rigorously designed and reported and consider peer-based online support approaches.

Identifying shared transcriptional risk patterns between atherosclerosis and cancer.

Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Numerous overlapping pathophysiologic mechanisms have been hypothesized to drive the development of both diseases. Further investigation of these common pathways could allow for the identification of mutually detrimental processes and therapeutic targeting to derive mutual benefit. In this study, we intersect transcriptomic datasets correlated with disease severity or patient outcomes for both cancer and atherosclerotic CVD. These analyses confirmed numerous pathways known to underlie both diseases, such as inflammation and hypoxia, but also identified several novel shared pathways. We used these to explore common translational targets by applying the drug prediction software, OCTAD, to identify compounds that simultaneously reverse the gene expression signature for both diseases. These analyses suggest that certain tumor-specific therapeutic approaches may be implemented so that they avoid cardiovascular consequences, and in some cases may even be used to simultaneously target co-prevalent cancer and atherosclerosis.

Risk of Cancer After Diagnosis of Cardiovascular Disease.

Background: Cardiovascular disease (CVD) and cancer share several risk factors. Although preclinical models show that various types of CVD can accelerate cancer progression, clinical studies have not determined the impact of atherosclerosis on cancer risk. Objectives: The objective of this study was to determine whether CVD, especially atherosclerotic CVD, is independently associated with incident cancer. Methods: Using IBM MarketScan claims data from over 130 million individuals, 27 million cancer-free subjects with a minimum of 36 months of follow-up data were identified. Individuals were stratified by presence or absence of CVD, time-varying analysis with multivariable adjustment for cardiovascular risk factors was performed, and cumulative risk of cancer was calculated. Additional analyses were performed according to CVD type (atherosclerotic vs nonatherosclerotic) and cancer subtype. Results: Among 27,195,088 individuals, those with CVD were 13% more likely to develop cancer than those without CVD (HR: 1.13; 95% CI: 1.12-1.13). Results were more pronounced for individuals with atherosclerotic CVD (aCVD), who had a higher risk of cancer than those without CVD (HR: 1.20; 95% CI: 1.19-1.21). aCVD also conferred a higher risk of cancer compared with those with nonatherosclerotic CVD (HR: 1.11; 95% CI: 1.11-1.12). Cancer subtype analyses showed specific associations of aCVD with several malignancies, including lung, bladder, liver, colon, and other hematologic cancers. Conclusions: Individuals with CVD have an increased risk of developing cancer compared with those without CVD. This association may be driven in part by the relationship of atherosclerosis with specific cancer subtypes, which persists after controlling for conventional risk factors.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Photoacoustic imaging has sufficient penetration and sensitivity to map and characterize human atherosclerotic plaque. Here, near infrared photoacoustic imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the near-infrared auto-photoacoustic (NIRAPA) signal, immunohistochemistry, spatial transcriptomics and proteomics were applied to adjacent sections of the plaque. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque.

Constrictive Pericarditis Revealing Rare Case of ALH Amyloidosis With Underlying Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia).

We present a case of pericardial amyloidosis with associated lymphoplasmacytic lymphoma in a patient with chronic worsening shortness of breath and cough. This case highlights the wide variation in the presentation of cardiac amyloidosis, and the rare occurrence of clinically significant light-chain and heavy-chain amyloidosis in the pericardium. (Level of Difficulty: Advanced.).

Profiling microbial community structures and functions in bioremediation strategies for treating 1,4-dioxane-contaminated groundwater.

Microbial community compositions and functional profiles were analyzed in microcosms established using aquifer materials from a former automobile factory site, where 1,4-dioxane was identified as the primary contaminant of concern. Propane or oxygen biostimulation resulted in limited 1,4-dioxane degradation, which was markedly enhanced with the addition of nutrients, resulting in abundant Mycobacterium and Methyloversatilis taxa and high expressions of propane monooxygenase gene, prmA. In bioaugmented treatments, Pseudonocardia dioxanivorans CB1190 or Rhodococcus ruber ENV425 strains dominated immediately after augmentation and degraded 1,4-dioxane rapidly which was consistent with increased representation of xenobiotic and lipid metabolism-related functions. Although the bioaugmented microbes decreased due to insufficient growth substrates and microbial competition, they did continue to degrade 1,4-dioxane, presumably by indigenous propanotrophic and heterotrophic bacteria, inducing similar community structures across bioaugmentation conditions. In various treatments, functional redundancy acted as buffer capacity to ensure a stable microbiome, drove the restoration of the structure and microbial functions to original levels, and induced the decoupling between basic metabolic functions and taxonomy. The results of this study provided valuable information for design and decision-making for ex-situ bioreactors and in-situ bioremediation applications. A metagenomics-based understanding of the treatment process will enable efficient and accurate adjustments when encountering unexpected issues in bioremediation.

SafeSpot: an innovative app and mental health support package for Scottish schools - a qualitative analysis as part of a mixed methods study.

AIMS: The aim of the study was to investigate teachers' and pupils' perceptions about the effect of the SafeSpot mental health curriculum on the well-being of young people and on their knowledge of mental health conditions. This trial intends to determine the acceptability and benefits of web and mobile technology in delivering emotional well-being in schools, through use of the SafeSpot programme. BACKGROUND: With 10% of young people aged 5 to 16 diagnosed with a mental disorder, there is pressure for schools to address their pupils' emotional well-being. However, many educators report that their schools have insufficient provisions and feel inadequately equipped to support pupils' mental health. METHODS: This qualitative analysis was embedded within a randomly allocated stepped-wedge design, conducted in six West of Scotland secondary schools. A total of 2320 pupils (aged 11 to 14 years) and 90 teachers were included. Young people's understanding of health-seeking, and teacher's confidence in delivering and accessing well-being information was assessed qualitatively. RESULTS: Qualitative analysis revealed themes highlighting the beneficial nature of SafeSpot, including pupil engagement, content of tutorials, perceived impact of SafeSpot and level of training provided for teachers. CONCLUSIONS: Web technology could potentially offer a more structured way for staff to support their pupils' mental health, whilst reducing stigma. SafeSpot was perceived, by pupils and teachers, to be engaging.

Reduced Intracerebral Hemorrhage and Perihematomal Edema Volumes in Diabetics on Sulfonylureas.

Background and Purpose- Sulfonylurea medications have been linked to reduced brain edema and improved outcome following ischemic stroke, but their effects on primary intracerebral hemorrhage (pICH) have not been thoroughly explored. Increasing ICH volume and perihematomal edema (PHE) volume are predictors of poor outcome in pICH. We investigated whether preexisting sulfonylurea use influenced ICH volume, PHE volume, and discharge disposition in patients with type 2 diabetes mellitus presenting with pICH. Methods- We performed a retrospective chart review of all diabetic patients presenting with pICH to 2 tertiary academic centers from 2006 to 2016. All patients with diabetes mellitus, pICH, admission computed tomography scan, and sulfonylurea use on admission were included in our study. For each case, 2-matched controls (admission date, age, hematoma location [deep versus lobar], use of antiplatelet, or anticoagulant) with diabetes mellitus and pICH were consecutively selected. ICH and PHE volumes were measured via region of interest analysis on admission computed tomography. To mitigate the influence of ICH volume on PHE, the PHE/ICH surface area ratio was calculated. Hospital discharge disposition was determined via chart abstraction. We used the Wilcoxon rank-sum test and Fisher exact test to compare cases and controls. Results- Of 317 patients screened, 21 sulfonylurea cases and 42-matched controls met criteria for study inclusion. Sulfonylurea cases had significantly lower admission ICH volumes (median, 4 mL; interquartile range [IQR], 2-30 versus median, 25 mL; IQR, 6-60; P=0.011), PHE volumes (median, 4 mL; IQR, 0.9-24 versus median, 17; IQR, 6-37; P=0.0095), and PHE/ICH surface area ratios (median, 0.28; IQR, 0.1-0.4 versus median, 0.43; IQR, 0.3-0.6; P=0.013) as compared with controls. Sulfonylureas were associated with improved discharge disposition ( P=0.0062). Conclusions- In patients with diabetes mellitus and pICH, sulfonylurea use predicted lower ICH and PHE volumes, lower relative PHE, and improved discharge disposition. Given the paucity of treatment options for pICH, further study of sulfonylureas is warranted.

Basal ganglia hemorrhage in a case report following spinal surgery.

BACKGROUND: Intracranial hemorrhage is a rare but potentially severe complication of spinal surgery. Most reported post-operative ICH cases consist of cerebellar hemorrhage. There are fewer reported cases of supratentorial ICH following spinal surgery. CASE PRESENTATION: A 56-year-old woman underwent spinal surgery complicated by bilateral supratentorial intraparenchymal basal ganglia hemorrhage with both intraventricular extension and subarachnoid hemorrhage in both cerebral hemispheres. CONCLUSION: The occurrence of neurological deterioration post-operatively following spinal surgery should alert physicians to the possibility of intracranial hemorrhage in order to facilitate rapid and optimal management. To our knowledge, this is the first case reporting basal ganglia hemorrhage following spinal surgery. Moreover, consideration should be given to the possibility of this complication prior to recommendation of elective spinal surgery.

Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.

Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. These findings provide a rationale for MAPK inhibition in SPRED1-deficient melanomas and introduce a zebrafish modeling approach that can be used more generally to dissect genetic interactions in cancer.

Neurocognitive performance profile postparathyroidectomy: a pilot study of computerized assessment.

BACKGROUND: Neurocognitive symptoms attributable to primary hyperparathyroidism are important diagnostic criteria, yet the basic characterization and assessment of neurocognitive deficits in primary hyperparathyroidism are not defined fully. METHODS: In this prospective pilot study, patients with unequivocal biochemical diagnosis of primary hyperparathyroidism were evaluated for neurocognitive performance preoperatively and postparathyroidectomy (2 weeks, 6 months) using a battery of computerized modular tests designed by LUMOSITY. The individual test scores and aggregate scores representing a subject's total neurocognitive performance profile were calculated. Statistical comparisons between groups were performed using univariate analysis and repeated measures of analysis of variance. RESULTS: In the study, 34 participants were assessed preoperatively; 18 completed all 3 assessments, 2 completed pretest and 6-month assessments, and 30 completed preoperative and 2-week postparathyroidectomy assessments. Primary hyperparathyroidism patients demonstrated significant deficits in memory, attention, mental flexibility, and speed of processing when compared with controls. Total neurocognitive performance profile score was significantly lower at the preoperative (P = .0001) and 2-week postparathyroidectomy (P = .0004) time points when compared with controls; this difference was bridged by 6 months postparathyroidectomy. CONCLUSION: Computerized neurocognitive performance profile assessment validated the neurocognitive benefits of parathyroidectomy. Additional study is needed to determine if this novel method provides long-term, objective, quantifiable, and accessible neurocognitive performance profile assessment in primary hyperparathyroidism patients and can serve as a valuable diagnostic and prognostic tool.

Cell cycle specific radiosensitisation by the disulfiram and copper complex.

The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 µM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively. The increased potency of ionising radiation treatment induced by DSF:Cu and/or gemcitabine was determined by clonogenic assay. Treatment with 0.3 µM DSF:Cu resulted in greater radiation kill, exemplified by dose enhancement factor values of 2.64 and 2.84 in SK-N-BE(2c) and UVW cells, respectively. Although DSF:Cu failed to sensitise S phase cells to irradiation, we observed that DSF:Cu radiosensitisation was potentiated by the S phase-specific cytotoxic drug gemcitabine. The efficacy of the combination treatment consisting of DSF:Cu, gemcitabine and ionising radiation was schedule-dependent. Together, these results describe cell cycle specific radiosensitisation by DSF:Cu. The well-established toxicity profiles of DSF and gemcitabine should facilitate their evaluation as a combination treatment in patients undergoing radiotherapy.

The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity.

Human chromosome ends are capped by shelterin, a protein complex that protects the natural ends from being recognized as sites of DNA damage and also regulates the telomere-replicating enzyme, telomerase. Shelterin includes the heterodimeric POT1-TPP1 protein, which binds the telomeric single-stranded DNA tail. TPP1 has been implicated both in recruiting telomerase to telomeres and in stimulating telomerase processivity (the addition of multiple DNA repeats after a single primer-binding event). Determining the mechanisms of these activities has been difficult, especially because genetic perturbations also tend to affect the essential chromosome end-protection function of TPP1 (refs 15-17). Here we identify separation-of-function mutants of human TPP1 that retain full telomere-capping function in vitro and in vivo, yet are defective in binding human telomerase. The seven separation-of-function mutations map to a patch of amino acids on the surface of TPP1, the TEL patch, that both recruits telomerase to telomeres and promotes high-processivity DNA synthesis, indicating that these two activities are manifestations of the same molecular interaction. Given that the interaction between telomerase and TPP1 is required for telomerase function in vivo, the TEL patch of TPP1 provides a new target for anticancer drug development.

Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice.

AIMS: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. MAIN METHODS: Forty-eight mice were studied in four groups (n=12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. KEY FINDINGS: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. SIGNIFICANCE: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE(-/-) mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.

Age-dependent renal cortical microvascular loss in female mice.

Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 µm) was decreased in all aged groups compared with young controls (30.3 ± 5.8 vessels/mm², P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 ± 1.7 vs. 17.2 ± 4.2 and 18 ± 3.0 vessels/mm², P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 µm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-ß signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.

Congruence among encounters, norms, crowding, and management in a marine protected area.

Over the past few decades, recreation and tourism use has increased at many marine protected areas, generating concerns about impacts of this increasing use on experiences and conditions at these areas (e.g., crowding, conflict). This article uses data from Molokini Shoal Marine Life Conservation District in Hawai'i to examine: (a) reported encounters, crowding, normative tolerances for various use levels, and support of use related management strategies at this site; and (b) whether users who encounter higher use levels than their norms feel more crowded and are more supportive of restrictive management strategies. Data were obtained from onsite pre-trip and post-trip questionnaires of 712 passengers on commercial snorkel and dive tours visiting this site. Norms were measured with acceptance of 12 photographs depicting levels of boat use. On average, users would accept seeing no more than approximately 16 boats at one time at Molokini and this number was observed on over 20% of trips to the site. Although the majority of users expected to escape crowds at Molokini, 67% felt crowded and up to 79% supported actions that would directly restrict use at this site (e.g., limit number of boats). Users who encountered more boats than their normative tolerance felt more crowded and were more supportive of these management strategies. Findings suggest that this marine protected area is operating over its capacity and management is needed to improve experiences and conditions.