The C-terminal domains of ADAMTS1 contain exosites involved in its proteoglycanase activity.

A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1) is a protease involved in fertilization, cancer, cardiovascular development, and thoracic aneurysms. Proteoglycans such as versican and aggrecan have been identified as ADAMTS1 substrates, and Adamts1 ablation in mice typically results in versican accumulation; however, previous qualitative studies have suggested that ADAMTS1 proteoglycanase activity is weaker than that of other family members such as ADAMTS4 and ADAMTS5. Here, we investigated the functional determinants of ADAMTS1 proteoglycanase activity. We found that ADAMTS1 versicanase activity is approximately 1000-fold lower than ADAMTS5 and 50-fold lower than ADAMTS4 with a kinetic constant (kcat/Km) of 3.6 × 103 M-1 s-1 against full-length versican. Studies on domain-deletion variants identified the spacer and cysteine-rich domains as major determinants of ADAMTS1 versicanase activity. Additionally, we confirmed that these C-terminal domains are involved in the proteolysis of aggrecan as well as biglycan, a small leucine-rich proteoglycan. Glutamine scanning mutagenesis of exposed positively charged residues on the spacer domain loops and loop substitution with ADAMTS4 identified clusters of substrate-binding residues (exosites) in ß3-ß4 (R756Q/R759Q/R762Q), ß9-ß10 (residues 828-835), and ß6-ß7 (K795Q) loops. This study provides a mechanistic foundation for understanding the interactions between ADAMTS1 and its proteoglycan substrates and paves the way for development of selective exosite modulators of ADAMTS1 proteoglycanase activity.

Neonatal hypoxia impairs serotonin release and cognitive functions in adult mice.

Children who experienced moderate perinatal asphyxia (MPA) are at risk of developing long lasting subtle cognitive and behavioral deficits, including learning disabilities and emotional problems. The prefrontal cortex (PFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin (5-HT) project to the PFC, and compounds modulating 5-HT activity influence emotion and cognition. Whether 5-HT dysregulations contribute to MPA-induced cognitive problems is unknown. We established a MPA mouse model, which displays recognition and spatial memory impairments and dysfunctional cognitive flexibility. We found that 5-HT expression levels, quantified by immunohistochemistry, and 5-HT release, quantified by in vivo microdialysis in awake mice, are reduced in PFC of adult MPA mice. MPA mice also show impaired body temperature regulation following injection of the 5-HT1A receptor agonist 8-OH-DPAT, suggesting the presence of deficits in 5-HT auto-receptor function on raphe neurons. Finally, chronic treatment of adult MPA mice with fluoxetine, an inhibitor of 5-HT reuptake transporter, or the 5-HT1A receptor agonist tandospirone rescues cognitive flexibility and memory impairments. All together, these data demonstrate that the development of 5-HT system function is vulnerable to moderate perinatal asphyxia. 5-HT hypofunction might in turn contribute to long-term cognitive impairment in adulthood, indicating a potential target for pharmacological therapies.

Associations between perinatal risk and physical health in pre-adolescence in the Adolescent Brain Cognitive Development (ABCD) Study®: the unexpected relationship with sleep disruption.

BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Development℠ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.

How long does it take to scale-up obesity prevention interventions?

OBJECTIVE: The scale-up of evidence-based interventions is necessary to reverse high rates of obesity. However, scale-up doesn't occur frequently nor in a timely manner. While it has been estimated that takes 14-17 years for research translation to occur, the time taken to scale-up prevention interventions is largely unknown. This study examined the time taken to scale-up obesity prevention interventions across four scale-up pathways. METHODS: A sample of obesity prevention interventions that had been scaled-up or implemented at scale were found using a structured search strategy. Included interventions were mapped against four scale-up pathways and timeframes associated with each stage of the scale-up pathway were identified to determine the time taken to scale-up. RESULTS: Of the 90 interventions found that were scaled-up to at least a city-wide level, less than half reported a comprehensive research pathway to scale-up and a third did not report any evidence of efficacy or effectiveness prior to scale-up. The time taken to scale-up ranged from 0 to 5 years depending on the pathway taken. Those following a comprehensive pathway took approximately 5 years to scale-up, while interventions that had only one evidence generating step took between 1 and 1.5 years to scale-up. For the remaining interventions, scale-up occurred immediately post-development without evidence generation. CONCLUSIONS: Our findings indicate that the scale-up of obesity prevention interventions can occur more quickly than previous estimates of 14-17 years. Our findings support previous research that scale-up of interventions occurs through a variety of pathways and often scale-up occurs in absence of prior evidence of effectiveness.

Spectrum of Cognitive Biases in Diagnostic Radiology.

Cognitive biases are systematic thought processes involving the use of a filter of personal experiences and preferences arising from the tendency of the human brain to simplify information processing, especially when taking in vast amounts of data such as from imaging studies. These biases encompass a wide spectrum of thought processes and frequently overlap in their concepts, with multiple biases usually in operation when interpretive and perceptual errors occur in radiology. The authors review the gamut of cognitive biases that occur in radiology. These biases are organized according to their expected stage of occurrence while the radiologist reads and interprets an imaging study. In addition, the authors propose several additional cognitive biases that have not yet, to their knowledge, been defined in the radiologic literature but are applicable to diagnostic radiology. Case examples are used to illustrate potential biases and their impact, with emergency radiology serving as the clinical paradigm, given the associated high imaging volumes, wide diversity of imaging examinations, and rapid pace, which can further increase a radiologist's reliance on biases and heuristics. Potential strategies to recognize and overcome one's personal biases at each stage of image interpretation are also discussed. Awareness of such biases and their unintended effects on imaging interpretations and patient outcomes may help make radiologists cognizant of their own biases that can result in diagnostic errors. Identification of cognitive bias in departmental and systematic quality improvement practices may represent another tool to prevent diagnostic errors in radiology. ©RSNA, 2024 See the invited commentary by Larson in this issue.

Real-world public health interventions demonstrate how research evidence informs program scale-up.

Evidence-based population interventions rely on intervention testing (efficacy and effectiveness trials) to determine what works to improve public health. We investigated the characteristics of real-world public health interventions to address obesity and explored the extent to which research testing was undertaken prior to scale-up. We identified 90 population health interventions targeting physical activity, nutrition or obesity-related health behaviours and collected publicly available information on their key characteristics and outcomes. We then assessed the differences between interventions that followed a research pathway and those that did not. Two-thirds (n = 60) of the interventions were reported as having followed a research pathway. Univariate logistic regression analysis revealed that these interventions were more likely to be health education interventions [odds ratio (OR): 5.56; 95% confidence interval (CI): 1.38-22.38], developed by research institutes (OR: 12.81; 95% CI: 3.47-47.34), delivered in North America (OR: 4.13; 95% CI: 1.61-10.62), and less likely to be owned (OR: 0.35; 95% CI: 0.14-0.88) or funded by government organizations (OR: 0.37; 95% CI: 0.14-0.95). Interventions that followed a research pathway were nearly three times more likely to have a positive impact on population health (OR: 2.72; 95% CI: 1.04-7.14). Interventions that followed a research pathway to scale-up were no more likely to be sustained longer than those that did not. Differences exist across real-world interventions between those that follow a research pathway to population-scale delivery and those that do not, regarding organizational and environmental context. A key benefit of research pathway to scale-up is the impact it has on health outcomes.

A prospective cohort study on the role of surgical mentorship on medical students' surgical experience and attitudes towards surgery.

BACKGROUND: Exposure to surgery during medical school is limited. We ran a mentorship scheme pairing students at a medical school with local surgeons to improve undergraduate insight. We evaluated the effectiveness of mentorship in increasing surgical exposure and drivers for students seeking surgical mentorship. METHODS: 35 surgeons across 7 specialties were recruited and matched with 37 students in years 2-4 for 7 months. Quantitative and qualitative evaluation was done with pre-, mid- and post-scheme questionnaires. Students rated confidence across pursuing a career in surgery, surgical exposure, career insight, understanding the application process, contacts, portfolio development, research knowledge and pursuing extra-curricular activities related to surgery using a 5-point Likert scale. Paired t-tests were performed to measure students' confidence before and after the scheme. RESULTS: Of students that completed all 3 questionnaires (n = 21), conducting research/audit was most frequently selected as a main goal (81.0%), followed by theatre experience (66.7%) and career progression support (28.6%). The number of students that had assisted in theatre increased by 50.0%. Confidence ratings across all domains increased with 7/8 (87.5%) exhibiting a statistically significant improvement (p < 0.05). The greatest improvement was seen in having adequate contacts in surgery from 2.05 to 3.33 (p = 0.00). 95.2% would recommend the scheme. CONCLUSIONS: Students gained significantly more surgical experience and were better equipped with the knowledge required to pursue a surgical career. Mentorship schemes are invaluable in supplementing the undergraduate curriculum and empowering students. TRIAL REGISTRATION: Ethical clearance granted by King's College London Research Ethics Committee, Reference Number MRSU-22/23-34530. .

The annotation and analysis of complex 3D plant organs using 3DCoordX.

A fundamental question in biology concerns how molecular and cellular processes become integrated during morphogenesis. In plants, characterization of 3D digital representations of organs at single-cell resolution represents a promising approach to addressing this problem. A major challenge is to provide organ-centric spatial context to cells of an organ. We developed several general rules for the annotation of cell position and embodied them in 3DCoordX, a user-interactive computer toolbox implemented in the open-source software MorphoGraphX. 3DCoordX enables rapid spatial annotation of cells even in highly curved biological shapes. Using 3DCoordX, we analyzed cellular growth patterns in organs of several species. For example, the data indicated the presence of a basal cell proliferation zone in the ovule primordium of Arabidopsis (Arabidopsis thaliana). Proof-of-concept analyses suggested a preferential increase in cell length associated with neck elongation in the archegonium of Marchantia (Marchantia polymorpha) and variations in cell volume linked to central morphogenetic features of a trap of the carnivorous plant Utricularia (Utricularia gibba). Our work demonstrates the broad applicability of the developed strategies as they provide organ-centric spatial context to cellular features in plant organs of diverse shape complexity.

Comparison of BACTEC versus conventional enrichment medium for peritoneal dialysate fluid culture.

BACKGROUND: Bacterial peritonitis remains a significant cause of mortality in patients on peritoneal dialysis (PD). Early detection of causative organisms and targeted antimicrobial treatment allow for better clinical outcomes. This study compares bacterial growth results from peritoneal dialysate in the BACTEC blood culture system vs. conventional culture. MATERIALS AND METHODS: We conducted a prospective study on 46 patients with 63 consecutive episodes of suspected PD peritonitis between August 2020 and August 2021. PD dialysate was simultaneously sent to the laboratory in both BACTEC and sterile bottles. BACTEC bottles were incubated in the BD BACTEC FX system for 5 days. PD effluent transported from the sterile bottles was centrifuged at 3,000 rpm for 15 minutes; the supernatant was inoculated into cooked-meat broth for enrichment. Both incubation methods were extended to 14 days if microorganisms were seen on the Gram-stained smear. Recovery of isolated micro-organisms and time to detection (TTD) were compared. RESULTS: 26 episodes of suspected PD peritonitis based on clinical criteria were identified during the study period. The sensitivity of the BACTEC and the conventional culture methods was 50% and 42.3%, respectively (p = 0.45). Seven samples had partial concordance or discordant results. McNemar's χ2-test revealed no statistical difference between either method (p = 0.45). TTD was 18.9 ± 24.4 hours via the BACTEC method vs. 37 ± 16.5 hours in conventional cultures (p = 0.014). CONCLUSION: The comparable sensitivities and similar yield in identifying pathogens could be due to the enrichment medium and prolonged incubation period. The shorter TTD for the BACTEC method could facilitate earlier confirmation of bacteriological diagnosis and subsequent treatment strategies.

Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review.

PURPOSE: Reperfusion therapy has greatly improved outcomes of ischaemic stroke but remains associated with haemorrhagic conversion and early deterioration in a significant proportion of patients. Outcomes in terms of function and mortality are mixed and the evidence for decompressive craniectomies (DC) in this context remains sparse. We aim to investigate the clinical efficacy of DC in this group of patients compared to those without prior reperfusion therapy. METHODS: A multicentre retrospective study was conducted between 2005 and 2020, and all patients with DC for large territory infarctions were included. Outcomes in terms of inpatient and long-term modified Rankin scale (mRS) and mortality were assessed at various time points and compared using both univariable and multivariable analyses. Favourable mRS was defined as 0-3. RESULTS: There were 152 patients included in the final analysis. The cohort had a mean age of 57.5 years and median Charlson comorbidity index of 2. The proportion of preoperative anisocoria was 15.1%, median preoperative Glasgow coma scale was 9, the ratio of left-sided stroke was 40.1%, and ICA infarction was 42.8%. There were 79 patients with prior reperfusion and 73 patients without. After multivariable analysis, the proportion of favourable 6-month mRS (reperfusion, 8.2%; no reperfusion, 5.4%) and 1-year mortality (reperfusion, 26.7%; no reperfusion, 27.3%) were similar in both groups. Subgroup analysis of thrombolysis and/or thrombectomy against no reperfusion was also unremarkable. CONCLUSION: Reperfusion therapy prior to DC performed for large territory cerebral infarctions does not affect the functional outcome and mortality in a well-selected patient population.

Initial Investigations of Intrinsically Disordered Regions in Inherited Retinal Diseases.

Intrinsically disordered regions (IDRs) are protein regions that are unable to fold into stable tertiary structures, enabling their involvement in key signaling and regulatory functions via dynamic interactions with diverse binding partners. An understanding of IDRs and their association with biological function may help elucidate the pathogenesis of inherited retinal diseases (IRDs). The main focus of this work was to investigate the degree of disorder in 14 proteins implicated in IRDs and their relationship with the number of pathogenic missense variants. Metapredict, an accurate, high-performance predictor that reproduces consensus disorder scores, was used to probe the degree of disorder as a function of the amino acid sequence. Publicly available data on gnomAD and ClinVar was used to analyze the number of pathogenic missense variants. We show that proteins with an over-representation of missense variation exhibit a high degree of disorder, and proteins with a high amount of disorder tolerate a higher degree of missense variation. These proteins also exhibit a lower amount of pathogenic missense variants with respect to total missense variants. These data suggest that protein function may be related to the overall level of disorder and could be used to refine variant interpretation in IRDs.

USP7 Inhibition Suppresses Neuroblastoma Growth via Induction of p53-Mediated Apoptosis and EZH2 and N-Myc Downregulation.

Neuroblastoma (NB) is a pediatric malignancy originating from neural crest cells of the sympathetic nervous system that accounts for 15% of all pediatric cancer deaths. Despite advances in treatment, high-risk NB remains difficult to cure, highlighting the need for novel therapeutic approaches. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that plays a critical role in tumor suppression and DNA repair, and USP7 overexpression has been associated with tumor aggressiveness in a variety of tumors, including NB. Therefore, USP7 is a potential therapeutic target for NB. The tumor suppressor p53 is a known target of USP7, and therefore reactivation of the p53 pathway may be an effective therapeutic strategy for NB treatment. We hypothesized that inhibition of USP7 would be effective against NB tumor growth. Using a novel USP7 inhibitor, Almac4, we have demonstrated significant antitumor activity, with significant decreases in both cell proliferation and cell viability in TP53 wild-type NB cell lines. USP7 inhibition in NB cells activated the p53 pathway via USP7 and MDM2 degradation, leading to reduced p53 ubiquitination and increased p53 expression in all sensitive NB cells. In addition, USP7 inhibition led to decreased N-myc protein levels in both MYCN-amplified and -nonamplified NB cell lines, but no correlation was observed between MYCN amplification and treatment response. USP7 inhibition induced apoptosis in all TP53 wild-type NB cell lines. USP7 inhibition also induced EZH2 ubiquitination and degradation. Lastly, the combination of USP7 and MDM2 inhibition showed enhanced efficacy. Our data suggests that USP7 inhibition may be a promising therapeutic strategy for children with high-risk and relapsed NB.

Shaping of a three-dimensional carnivorous trap through modulation of a planar growth mechanism.

Leaves display a remarkable range of forms, from flat sheets with simple outlines to cup-shaped traps. Although much progress has been made in understanding the mechanisms of planar leaf development, it is unclear whether similar or distinctive mechanisms underlie shape transformations during development of more complex curved forms. Here, we use 3D imaging and cellular and clonal analysis, combined with computational modelling, to analyse the development of cup-shaped traps of the carnivorous plant Utricularia gibba. We show that the transformation from a near-spherical form at early developmental stages to an oblate spheroid with a straightened ventral midline in the mature form can be accounted for by spatial variations in rates and orientations of growth. Different hypotheses regarding spatiotemporal control predict distinct patterns of cell shape and size, which were tested experimentally by quantifying cellular and clonal anisotropy. We propose that orientations of growth are specified by a proximodistal polarity field, similar to that hypothesised to account for Arabidopsis leaf development, except that in Utricularia, the field propagates through a highly curved tissue sheet. Independent evidence for the polarity field is provided by the orientation of glandular hairs on the inner surface of the trap. Taken together, our results show that morphogenesis of complex 3D leaf shapes can be accounted for by similar mechanisms to those for planar leaves, suggesting that simple modulations of a common growth framework underlie the shaping of a diverse range of morphologies.

Spectrum of MRI Features of Mucin-producing Neoplasms in the Abdomen and Pelvis.

Mucin-producing neoplasms in the abdomen and pelvis are a distinct entity, separate from simple fluid-containing neoplasms and loculated fluid collections. Mucin is a thick gelatinous substance and-owing to its high water content-has imaging features that can be mistaken for those of simple fluid-containing neoplasms with multiple imaging modalities. However, mucin-producing neoplasms arise from specific organs in the abdomen and pelvis, with unique imaging appearances, knowledge of which is important to guide accurate diagnosis and management. With its large field of view and high soft-tissue resolution, MRI has advantages over other imaging modalities in characterizing these neoplasms. The authors focus on the spectrum of MRI features of such mucin-producing neoplasms and illustrate how-despite a varied organ origin-some of these neoplasms share similar MRI and histopathologic features, thereby helping narrow the differential diagnosis. One common finding in these tumors is that the presence of internal complexity and solid enhancing components increases as the degree of malignant transformation increases. Lack of internal complexity generally indicates benignity. These tumors have a varied range of prognosis; for example, a low-grade appendiceal mucinous neoplasm is indicative of a good prognosis, while a mucinous tumor of the rectum is known to manifest at an early age with aggressive behavior and poorer prognosis compared with its nonmucinous counterpart. Online supplemental material is available for this article. ©RSNA, 2022.

Management of Patients With Common Bile Duct Dilatation Without a Sonographic Evident Cause: Evaluating the Yield of Subsequent Magnetic Resonance Imaging and Findings Correlated With Causative Pancreaticobiliary Pathology.

OBJECTIVES: The aims of the study were to evaluate the yield of magnetic resonance imaging (MRI) in patients with common bile duct (CBD) dilatation without a sonographic evident cause and to investigate sonographic and laboratory findings at presentation that might predict identification of underlying pancreaticobiliary pathology. METHODS: Included were consecutive patients in whom MRI was performed for further evaluation of CBD dilatation detected on ultrasound (US), without a sonographic evident cause, from January 1, 2014, to December 31, 2014. Magnetic resonance imaging and clinical data were retrospectively reviewed. Patients were divided into two groups: patients with and without identified underlying causative pancreaticobiliary pathology. Ultrasound findings and laboratory results at presentation were compared between groups to identify findings suggestive of underlying pancreaticobiliary pathology. RESULTS: Fifty-seven patients, with a mean age of 54 ± 16 years including 37 females (65%), underwent MRI. Specific pancreaticobiliary causes for CBD dilatation were identified in 38 patients (66%, 31 benign and 7 malignant). In the remaining patients, no cause was identified in 17 (30%) and MRIs were nondiagnostic in 2 patients. Magnetic resonance imaging accuracy for correctly identifying the underlying cause of CBD dilatation was 91%. Patients with associated intrahepatic bile duct dilatation on US and elevated alanine aminotransferase and alkaline phosphatase were more likely to have underlying pancreaticobiliary pathology (P < 0 .05). No patient with initial negative MRI had pancreaticobiliary malignancy. CONCLUSIONS: Magnetic resonance imaging seems to be an accurate noninvasive method for identifying the underlying cause in most patients with CBD dilatation on US and in excluding pancreaticobiliary malignancy. Patients with associated intrahepatic bile duct dilatation and/or elevated liver enzymes are at higher risk of harboring underlying pancreaticobiliary pathology.

Assessing the scalability of an integrated falls prevention service for community-dwelling older people: a mixed methods study.

BACKGROUND: There is growing acknowledgement of the need for a phased approach to scaling up health interventions, beginning with an assessment of 'scalability', that is, the capacity of an individual intervention to be scaled up. This study aims to assess the scalability of a multi-component integrated falls prevention service for community-dwelling older people and to examine the applicability of the Intervention Scalability Assessment Tool (ISAT). The ISAT consists of 10 domains for consideration when determining the scalability of an intervention, and each domain comprises a series of questions aimed at examining readiness for scale-up. METHODS: Multiple methods were used sequentially as recommended by the ISAT: a review of policy documents, results from a service evaluation and falls-related literature; one-to-one interviews (n = 11) with key stakeholders involved in management and oversight of the service; and a follow-up online questionnaire (n = 10) with stakeholders to rate scalability and provide further feedback on reasons for their scores. RESULTS: Three of the ISAT domains were rated highly by the participants. Analysis of the qualitative feedback and documents indicated that the issue of falls prevention among older people was of sufficient priority to warrant scale-up of the service and that the service aligned with national health policy priorities. Some participants also noted that benefits of the service could potentially outweigh costs through reduced hospital admissions and serious injuries such as hip fracture. The remaining domains received a moderate score from participants, however, indicating considerable barriers to scale-up. In the qualitative feedback, barriers identified included the perceived need for more healthcare staff to deliver components of the service, for additional infrastructure such as adequate room space, and for an integrated electronic patient management system linking primary and secondary care and to prevent duplication of services. CONCLUSIONS: Plans to scale up the service are currently under review given the practical barriers that need to be addressed. The ISAT provides a systematic and structured framework for examining the scalability of this multi-component falls prevention intervention, although the iterative nature of the process and detailed and technical nature of its questions require considerable time and knowledge of the service to complete.

Understanding the bigger picture: syndemic interactions of the immigrant and refugee context with the lived experience of diabetes and obesity.

BACKGROUND: Providing contextually appropriate care and interventions for people with diabetes and/or obesity in vulnerable situations within ethnocultural newcomer communities presents significant challenges. Because of the added complexities of the refugee and immigrant context, a deep understanding of their realities is needed. Syndemic theory sheds light on the synergistic nature of stressors, chronic diseases and environmental impact on immigrant and refugee populations living in vulnerable conditions. We used a syndemic perspective to examine how the migrant ethnocultural context impacts the experience of living with obesity and/or diabetes, to identify challenges in their experience with healthcare. METHODS: This qualitative participatory research collaborated with community health workers from the Multicultural Health Brokers Cooperative of Edmonton, Alberta. Study participants were people living with diabetes and/or obesity from diverse ethnocultural communities in Edmonton and the brokers who work with these communities. We conducted 3 focus groups (two groups of 8 and one of 13 participants) and 22 individual interviews (13 community members and 9 brokers). The majority of participants had type 2 diabetes and 4 had obesity. We conducted a thematic analysis to explore the interactions of people's living conditions with experiences of: 1) diabetes and obesity; and 2) healthcare and resources for well-being. RESULTS: The synergistic effects of pre- and post-immigration stressors, including lack of social network cultural distance, and poverty present an added burden to migrants' lived experience of diabetes/obesity. People need to first navigate the challenges of immigration and settling into a new environment in order to have capacity to manage their chronic diseases. Diabetes and obesity care is enhanced by the supportive role of the brokers, and healthcare providers who have an awareness of and consideration for the contextual influences on patients' health. CONCLUSIONS: The syndemic effects of the socio-cultural context of migrants creates an additional burden for managing the complexities of diabetes and obesity that can result in inadequate healthcare and worsened health outcomes. Consequently, care for people with diabetes and/or obesity from vulnerable immigrant and refugee situations should include a holistic approach where there is an awareness of and consideration for their context.

Understanding the sustainment of population health programmes from a whole-of-system approach.

BACKGROUND: Population health prevention programmes are needed to reduce the prevalence of chronic diseases. Nevertheless, sustaining programmes at a population level is challenging. Population health is highly influenced by social, economic and political environments and is vulnerable to these system-level changes. The aim of this research was to examine the factors and mechanisms contributing to the sustainment of population prevention programmes taking a systems thinking approach. METHODS: We conducted a qualitative study through interviews with population health experts working within Australian government and non-government agencies experienced in sustaining public health programs at the local, state or national level (n = 13). We used a deductive thematic approach, grounded in systems thinking to analyse data. RESULTS: We identified four key barriers affecting program sustainment: 1) short term political and funding cycles; 2) competing interests; 3) silo thinking within health service delivery; and 4) the fit of a program to population needs. To overcome these barriers various approaches have centred on the importance of long-range planning and resourcing, flexible program design and management, leadership and partnerships, evidence generation, and system support structures. CONCLUSION: This study provides key insights for overcoming challenges to the sustainment of population health programmes amidst complex system-wide changes.

Crowdfunding for Gender-Affirming Mastectomy: Balancing Fundraising With Loss of Privacy.

INTRODUCTION: Limitations in insurance coverage may cause patients to turn to crowdfunding to raise money for gender-affirming procedures. In this study, we analyze the impact of Medicaid insurance coverage on gender-affirming mastectomy campaigns posted on GoFundMe.com. METHODS: Between March 1 and 12, 2021, we accessed GoFundMe.com to analyze available campaigns requesting monetary contributions for gender-affirming mastectomy. Campaigns were identified using the search term "top surgery" followed by the state's name. Duplicate campaigns, campaigns whose primary goal was not gender-affirming mastectomy, and ongoing campaigns were excluded. Campaigns were then categorized according to their state's coverage of gender-affirming surgery: explicit exclusion (EE), explicit inclusion (EI), or no explicit statement of gender-affirming care. We collected data on the number of donors and shares, the fundraising goal, and the total amount raised for each campaign. Common themes within campaign narratives were identified and assessed by each reviewer. Finally, we collected data on the photographs posted by campaign creators. RESULTS: Our search yielded 790 campaigns, with an overall mean of 58 ± 99 donors and 212 ± 288 shares. The mean fundraising goal and amount raised among all campaigns were $6811 ± $5027 and $2579 ± $3072, respectively. Fundraising goals were most likely to be met in an EI state than an EE state (26.3% vs 8.1%; P < 0.001). The mean amount sought was highest in EE states and lowest in EI states, whereas the mean amount raised was lowest in EE states and highest in EI states. Of the campaigns, 97.1% mentioned personal or situational characteristics in the narrative section; 16.2% of all campaigns expressed negative feelings about posting on GoFundMe.com to raise money for their surgeries. CONCLUSION: Disparities in health care coverage of gender-affirming surgeries were seen between state categories, with a decreased need for crowdfunding in states explicitly including coverage of gender-affirming surgery. Many transgender patients used crowdfunding to pay for transition-related health care costs, relying on the kindness of strangers and their social network at the expense of their personal privacy. Expansion of legislative coverage of gender-affirming surgeries may alleviate some of this financial burden and reduce transgender patients' reliance on crowdfunding campaigns.

Yield of pelvic CT in emergency department patients undergoing CT torso for generalized or multiple complaints.

PURPOSE: To evaluate the utility of pelvic computed tomography (CT) in emergency department (ED) patients undergoing chest CT angiogram (CTA) for chest pain or suspected pulmonary embolism (PE) followed by abdominopelvic CT in the same session for additional multisystem or generalized complaints. METHODS: This retrospective study included consecutive adult ED patients from January 2017 to December 2019 who underwent CTA for suspected PE followed by portovenous abdominopelvic CT for multisystem or generalized complaints. Patient demographics, vitals, laboratory values, exam indication, malignancy history, and recent surgery/intervention were recorded. CT reports were reviewed for acute chest, abdomen, and/or pelvic pathology. RESULTS: There were 400 patients with 243 (61%) women and mean age of 59.8 years. Acute pelvic findings were seen in 11% (45/400). In 53% (24/45) of these, pelvic pathology could be diagnosed based on the abdominal portion of the CT. Five percent (21/400) of patients demonstrated isolated acute pelvic findings with 86% of these (18/21) clinically suspected prior to imaging. Acute pelvic pathology was associated with female gender (p = 0.015) and elevated white blood cell count (WBC) (p = 0.03). Specific pelvic CT indications and female gender were significantly associated with (p = 0.02 each) and independent predictors of isolated acute pelvic pathology. CONCLUSION: In ED patients undergoing chest CTA for chest pain or suspected PE combined with abdominopelvic CT, the presence of acute pelvic-related pathology not visualized on abdominal CT is low. For this ED patient cohort, pelvic CT may not be necessary in men with normal WBC and a low pre-imaging clinical suspicion for acute pelvic pathology.