Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

Microplastics in human urine: Characterisation using µFTIR and sampling challenges using healthy donors and endometriosis participants.

Microplastics (MPs) are found in all environments, within the human food chain, and have been recently detected in several human tissues. The objective herein was to undertake an analysis of MP contamination in human urine samples, from healthy individuals and participants with endometriosis, with respect to their presence, levels, and the characteristics of any particles identified. A total of 38 human urine samples and 15 procedural blanks were analysed. MPs were characterised using µFTIR spectroscopy (size limitation of 5 µm) and SEM-EDX. In total, 123 MP particles consisting of 22 MP polymer types were identified within 17/29 of the healthy donor (10 mL) urine samples, compared with 232 MP particles of differing 16 MP polymer types in 12/19 urine samples from participants with endometriosis. Healthy donors presented an unadjusted average of 2589 ± 2931 MP/L and participants with endometriosis presented 4724 ± 9710 MP/L. Polyethylene (PE)(27%), polystyrene (PS)(16%), resin and polypropylene (PP)(both 12%) polymer types were most abundant in healthy donor samples, compared with polytetrafluoroethylene (PTFE) (59%), and PE (16%) in samples from endometriosis participants. The MP levels within healthy and endometriosis participant samples were not significantly different. However, the predominant polymer types varied, and the MPs from the metal catheter-derived endometriosis participant samples and healthy donors were significantly smaller than those observed in the procedural blanks. The procedural blank samples comprised 62 MP particles of 10 MP polymer types, mainly PP (27%), PE (21%), and PS (15%) with a mean ± SD of 17 ± 18, highlighting the unavoidable contamination inherent in measurement of MPs from donors. This is the first evidence of MP contamination in human urine with polymer characterisation and accounting for procedural blanks. These results support the phenomenon of transport of MPs within humans, specifically to the bladder, and their characterisation of types, shapes and size ranges identified therein.

Promising Themes for Electronic Cigarette Prevention Campaigns for Youth and Young Adults.

INTRODUCTION: Electronic cigarettes (e-cigarettes) are the most widely used tobacco product by youth and young adults in the United States. Effective prevention campaigns require the identification of appropriate content focus for message construction. AIMS AND METHODS: A sample of 2622 youth and young adults ages 15-24 were recruited through social media advertisements and completed an online survey. Respondents reported current e-cigarette use or intention to use if not currently using. They also indicated agreement or disagreement with 75 e-cigarette-related beliefs representing 16 themes. The relative promise of each theme/belief for campaign messaging was investigated by examining its association with the behavior/intention outcomes and the opportunity for positive change in its distribution (room to move). RESULTS: All themes showed significant associations with the behavior (ORs = 2.49-19.04) and intention (ORs = 2.21-6.11) outcomes. Room to move for themes ranged from 32.9% to 96.3% in behavior analysis and 15.6-93.9% in intention analysis. A normed relative promise index (M = 50, SD = 17) showed flavors (72), comparison to cigarettes (69), and relaxation and mental health (68) as the top ranked themes. Subgroup analyses by demographics revealed few differences. Results on the belief level were largely consistent with those on the theme level. CONCLUSIONS: Data from this study provide timely evidence for the relative value of various themes/beliefs as potential targets for message development in e-cigarette prevention campaigns. The final selection of target themes/beliefs requires consideration of openness to persuasion, which may be informed by additional testing. IMPLICATIONS: Electronic cigarettes (e-cigarettes) are the most widely used tobacco products among youth and young adults in the United States. This study adds new evidence on the relative promise of a wide range of e-cigarette beliefs and belief clusters (themes) as potential targets for message development in educational campaigns. This evidence is important to consider in future campaign efforts directed at the youth and young adult populations in the United States.

Engineering subarachnoid trabeculae with electrospun poly(caprolactone) (PCL) scaffolds to study leptomeningeal metastasis in medulloblastoma.

Leptomeningeal metastasis (LM) occurs when cancer cells infiltrate the subarachnoid space (SAS) and metastasize to the fibrous structures that surround the brain and spinal cord. These structures include the leptomeninges (i.e., the pia mater and arachnoid mater), as well as subarachnoid trabeculae, which are collagen-rich fibers that provide mechanical structure for the SAS, support resident cells, and mediate flow of cerebrospinal fluid (CSF). Although there is a strong expectation that the presence of fibers within the SAS influences LM to be a major driver of tumor progression and lethality, exactly how trabecular architecture relates to the process of metastasis in cancer is poorly understood. This lack of understanding is likely due in part to the difficulty of accessing and manipulating this tissue compartment in vivo. Here, we utilized electrospun polycaprolactone (PCL) to produce structures bearing remarkable morphological similarity to native SAS fiber architecture. First, we profiled the native architecture of leptomeningeal and trabecular fibers collected from rhesus macaque monkeys, evaluating both qualitative and quantitative differences in fiber ultrastructure for various regions of the CNS. We then varied electrospinning parameters to produce a small library of PCL scaffolds possessing distinct architectures mimicking the range of fiber properties observed in vivo. For proof of concept, we studied the metastasis-related behaviors of human pediatric medulloblastoma cells cultured in different fiber microenvironments. These studies demonstrated that a more open, porous fiber structure facilitates DAOY cell spread across and infiltration into the meningeal mimic. Our results present a new tissue engineered model of the subarachnoid space and affirm the expectation that fiber architecture plays an important role in mediating metastasis-related behaviors in an in vitro model of pediatric medulloblastoma.

Public Education Can Be Used to Increase Support for Equity in Cannabis Policy.

Objectives: States that are legalizing cannabis for adult use are increasingly focused on equity, with the goal of repairing some of the harm caused by the War on Drugs. This study explains and describes the emphasis states are placing on equity and assesses whether public education can be used to increase public support for equity-focused cannabis policies. Methods: We conducted an online survey of 893 New Jersey adults in August and September of 2021, just as state's Cannabis Regulatory Commission was publishing the first set of regulations for the legal sale and use of cannabis for adults age 21 and older. The study included an experimental design, in which half of respondents viewed an educational message about equity-focused cannabis policies before answering survey questions, and the other half did not. Results: Few participants (24.9%) were familiar with the concept of equity in cannabis policy, and a substantial proportion-from about 20% to 35%-provided a "neutral" or "don't know" response when asked about support for specific policies. Exposure to an educational message was associated with greater perceived importance of equity in cannabis policy (p < 0.05) and greater support for equity-focused policies. Specifically, participants who saw an educational message had greater agreement that New Jersey should provide priority licensing (p < 0.01) and grants (p < 0.001) to people who have been arrested for cannabis, and who now want to participate in the legal cannabis industry. Conclusions: Cannabis regulators, public health professionals, and people working to advance racial justice may be able to advance state equity goals and remedy some of the harm from the War on Drugs by expanding public education campaigns to include equity messages.

Cannabis Policy in the 21st Century: Mandating an Equitable Future and Shedding the Racist Past.

The cannabis legalization movement in the United States has experienced unprecedented success in the past decade due to a wave of grassroots reforms in states across the country. The current legalization movement began in 2012, when Colorado and Washington became the first two states to legalize the use and sale of cannabis for adults aged ≥ 21 years. Since then, the use of cannabis has been legalized in 21 states, Guam, the Northern Mariana Islands, and Washington, DC. Many of these states have explicitly framed the law change as a rejection of the War on Drugs and its harms, felt disproportionately in Black and Brown communities. However, racial inequities in cannabis arrests have increased in states that have legalized cannabis for adult use. Moreover, states working to implement social equity and community reinvestment programs have made little progress toward their goals. This commentary describes how US drug policy, racist in intention, gave way to drug policy that perpetuates racism, even when its ostensible or stated goal is equity. As the United States prepares for national legalization of cannabis, it is critical that we break away from past legislation and mandate equity in cannabis policy. Developing meaningful mandates will require us to acknowledge our history of using drug policy for the racist goals of social control and extortion, study the experience of states that are trying to implement social equity programs, listen to Black leaders and other leaders of color who have developed guidance for equity-focused cannabis policy, and commit to a new paradigm. If we are willing to do these things, we may be able to legalize cannabis in an anti-racist way that will stop causing harm and enable us to effectively implement reparative practices.

Perceived Message Effectiveness and Campaign-Targeted Beliefs: Evidence of Reciprocal Effects in Youth Tobacco Prevention.

Perceived message effectiveness (PE) has been widely used in campaign formative research and evaluation. The relationship between PE and actual message effectiveness (AE) is often assumed to be causal and unidirectional, but careful conceptualization and empirical testing of this and other causal possibilities are generally lacking. In this study, we investigated the potential reciprocity in the relationship between PE and AE in the context of a national youth tobacco education campaign. In so doing, we also sought to generate much needed evidence on PE's utility to predict campaign-targeted outcomes in youth tobacco prevention. Using five waves of campaign evaluation data (N = 1,128), we found significant lagged associations between PE and campaign-targeted beliefs, and vice versa. These results suggest a dynamic, mutually influencing relationship between PE and AE and call for greater attention to such dynamics in campaign research.

Applicability of Narrow Groove Theory in Designing Washout Features for Rotary Blood Pumps.

High and low shear regions in rotary blood pumps require sufficient washout flow to minimize blood residence time, thereby preventing hemolysis or regions of stasis that can lead to pump thrombosis. Spiral groove bearings (SGBs) both enhance pump washout and reduce erythrocyte exposure to high shear. Narrow groove theory (NGT) has been used as an analytical tool to estimate the flow performance of a flat SGB during the design stage. However, NGT cannot accurately predict the performance of a conical SGB. In this study, we formulated an analytical model from the established NGT by adding an inertia correction term to incorporate variations in centrifugal force, which improved washout prediction in a conical SGB. The modified NGT model was then validated by comparison with experimental results. The results show that the modified NFT analytical model can reasonably predict washout rate when the spiral groove geometry favors creep flow conditions. The conical half angle of the SGB had the most significant impact on washout, with a decrease in half angle leading to large increases in wash-out flow. Small half angles also maintained viscous pumping at larger Reynolds numbers. In summary, the modified NGT can be a useful tool for designing conical SGBs for rotary blood pump washout within the creep flow regime.

Perceptions of U.S. and Canadian Cannabis Package Warnings Among U.S. Adults.

BACKGROUND: Cannabis warning labels can communicate risks, but there is little research on warning perceptions and differences by product type. METHODS: In a 2019 online survey, 1,000 U.S. adults (500 cannabis users and 500 cannabis non-users who used tobacco) were randomly assigned to view no warning or one of four U.S. or Canadian warnings displayed on images of packaging for dried flower or edible cannabis. The warnings described cannabis risks related to psychosis, addiction, lack of FDA oversight, and impaired driving. We used linear regression to examine perceptions of warnings and product harm as a function of product type (dried or edible) and warning. We examined which warning participants selected as most effective for discouraging youth use and impaired driving. RESULTS: Participants found the addiction warning (cannabis users: B = -1.04, p < 0.001; cannabis non-users: B = 1.17, p < 0.001) and psychosis warning (users: B = -0.65, p < 0.05; non-users: B = -0.71, p < 0.05) less believable than the driving warning but indicated that they learned more from the psychosis warning than the driving warning (users: B = 0.88, p < 0.01; non-users (B = 1.60, p < 0.001). Participants viewing any warning considered smoking cannabis to be more harmful than those viewing no warning (all p < 0.05). The psychosis warning was most frequently selected as the best warning for discouraging youth use. CONCLUSIONS: Warnings have the potential to educate consumers and impact cannabis harm perceptions. Warnings have similar effects across product types, potentially eliminating the need for product type-specific warnings. The association of cannabis use with risk for psychosis, a topic addressed in Canadian warnings, could be a useful topic of focus in U.S. warnings.

Enteroaggregative E. coli Adherence to Human Heparan Sulfate Proteoglycans Drives Segment and Host Specific Responses to Infection.

Enteroaggregative Escherichia coli (EAEC) is a significant cause of acute and chronic diarrhea, foodborne outbreaks, infections of the immunocompromised, and growth stunting in children in developing nations. There is no vaccine and resistance to antibiotics is rising. Unlike related E. coli pathotypes that are often associated with acute bouts of infection, EAEC is associated with persistent diarrhea and subclinical long-term colonization. Several secreted virulence factors have been associated with EAEC pathogenesis and linked to disease in humans, less certain are the molecular drivers of adherence to the intestinal mucosa. We previously established human intestinal enteroids (HIEs) as a model system to study host-EAEC interactions and aggregative adherence fimbriae A (AafA) as a major driver of EAEC adherence to HIEs. Here, we report a large-scale assessment of the host response to EAEC adherence from all four segments of the intestine across at least three donor lines for five E. coli pathotypes. The data demonstrate that the host response in the duodenum is driven largely by the infecting pathotype, whereas the response in the colon diverges in a patient-specific manner. Major pathways altered in gene expression in each of the four enteroid segments differed dramatically, with responses observed for inflammation, apoptosis and an overwhelming response to different mucin genes. In particular, EAEC both associated with large mucus droplets and specific mucins at the epithelial surface, binding that was ameliorated when mucins were removed, a process dependent on AafA. Pan-screening for glycans for binding to purified AafA identified the human ligand as heparan sulfate proteoglycans (HSPGs). Removal of HSPG abrogated EAEC association with HIEs. These results may mean that the human intestine responds remarkably different to distinct pathobionts that is dependent on the both the individual and intestinal segment in question, and uncover a major role for surface heparan sulfate proteoglycans as tropism-driving factor in adherence and/or colonization.

British Society of Echocardiography Departmental Accreditation Standards 2019 with input from the Intensive Care Society.

This article sets out a summary of standards for departmental accreditation set by the British Society of Echocardiography (BSE) Departmental Accreditation Committee. Full accreditation standards are available at www.bsecho.org. The BSE were the first national organisation to establish a quality standards framework for departments that support the practice of individual echocardiographers. This is an updated version which recognises that, not only should all echocardiographers be individually accredited as competent to practice, but that departments also need to be well organised and have the facilities, equipment and processes to ensure the services they deliver are of an appropriate clinical standard. In combination with individual accreditation, departmental accreditation lays down standards to help ensure safe and effective patient care. These standards supersede the 2012 BSE Departmental Accreditation Standards. Standards are set to cover all potential areas of practice, including transthoracic (level 2) echocardiography, transoesophageal echocardiography, stress echocardiography, training, and emergency (level 1) echocardiography. The emergency echocardiography standard is a new addition to departmental accreditation and has been developed with input from the Intensive Care Society.

Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment.

Discrete subaortic stenosis (DSS) is an obstruction of the left ventricular outflow tract (LVOT) due to the formation of a fibromuscular membrane upstream of the aortic valve. DSS is a major risk factor for aortic regurgitation (AR), which often persists after surgical resection of the membrane. While the etiology of DSS and secondary AR is largely unknown, the frequent association between DSS and aortoseptal angle (AoSA) abnormalities has supported the emergence of a mechanobiological pathway by which hemodynamic stress alterations on the septal wall could trigger a biological cascade leading to fibrosis and membrane formation. The resulting LVOT flow disturbances could activate the valve endothelium and contribute to AR. In an effort to assess this hypothetical mechano-etiology, this study aimed at isolating computationally the effects of AoSA abnormalities on septal wall shear stress (WSS), and the impact of DSS on LVOT hemodynamics. Two-dimensional computational fluid dynamics models featuring a normal AoSA (N-LV), a steep AoSA (S-LV), and a steep AoSA with a DSS lesion (DSS-LV) were designed to compute the flow in patient-specific left ventricles (LVs). Boundary conditions consisted of transient velocity profiles at the mitral inlet and LVOT outlet, and patient-specific LV wall motion. The deformation of the DSS lesion was computed using a two-way fluid-structure interaction modeling strategy. Turbulence was accounted for via implementation of the k-ω turbulence model. While the N-LV and S-LV models generated similar LVOT flow characteristics, the DSS-LV model resulted in an asymmetric LVOT jet-like structure, subaortic stenotic conditions (up to 2.4-fold increase in peak velocity, 45% reduction in effective jet diameter vs. N-LV/S-LV), increased vorticity (2.8-fold increase) and turbulence (5- and 3-order-of-magnitude increase in turbulent kinetic energy and Reynolds shear stress, respectively). The steep AoSA subjected the septal wall to a 23% and 69% overload in temporal shear magnitude and gradient, respectively, without any substantial change in oscillatory shear index. This study reveals the existence of WSS overloads on septal wall regions prone to DSS lesion formation in steep LVOTs, and the development of highly turbulent, stenotic and asymmetric flow in DSS LVOTs, which support a possible mechano etiology for DSS and secondary AR.

Mechanically tunable coaxial electrospun models of YAP/TAZ mechanoresponse and IGF-1R activation in osteosarcoma.

Current in vitro methods for assessing cancer biology and therapeutic response rely heavily on monolayer cell culture on hard, plastic surfaces that do not recapitulate essential elements of the tumor microenvironment. While a host of tumor models exist, most are not engineered to control the physical properties of the microenvironment and thus may not reflect the effects of mechanotransduction on tumor biology. Utilizing coaxial electrospinning, we developed three-dimensional (3D) tumor models with tunable mechanical properties in order to elucidate the effects of substrate stiffness and tissue architecture in osteosarcoma. Mechanical properties of coaxial electrospun meshes were characterized with a series of macroscale testing with uniaxial tensile testing and microscale testing utilizing atomic force microscopy on single fibers. Calculated moduli in our models ranged over three orders of magnitude in both macroscale and microscale testing. Osteosarcoma cells responded to decreasing substrate stiffness in 3D environments by increasing nuclear localization of Hippo pathway effectors, YAP and TAZ, while downregulating total YAP. Additionally, a downregulation of the IGF-1R/mTOR axis, the target of recent clinical trials in sarcoma, was observed in 3D models and heralded increased resistance to combination chemotherapy and IGF-1R/mTOR targeted agents compared to monolayer controls. In this study, we highlight the necessity of incorporating mechanical cues in cancer biology investigation and the complexity in mechanotransduction as a confluence of stiffness and culture architecture. Our models provide a versatile, mechanically variable substrate on which to study the effects of physical cues on the pathogenesis of tumors. STATEMENT OF SIGNIFICANCE: The tumor microenvironment plays a critical role in cancer pathogenesis. In this work, we engineered 3D, mechanically tunable, coaxial electrospun environments to determine the roles of the mechanical environment on osteosarcoma cell phenotype, morphology, and therapeutic response. We characterize the effects of varying macroscale and microscale stiffnesses in 3D environments on the localization and expression of the mechanoresponsive proteins, YAP and TAZ, and evaluate IGF-1R/mTOR pathway activation, a target of recent clinical trials in sarcoma. Increased nuclear YAP/TAZ was observed as stiffness in 3D was decreased. Downregulation of the IGF-1R/mTOR cascade in all 3D environments was observed. Our study highlights the complexity of mechanotransduction in 3D culture and represents a step towards controlling microenvironmental elements in in vitro cancer investigations.

Impact of The Real Cost Media Campaign on Youth Smoking Initiation.

INTRODUCTION: The purpose of this study was to assess the relationship between youth exposure to the U.S. Food and Drug Administration's national tobacco public education campaign, The Real Cost, and changes in smoking initiation. METHODS: From November 2013 to November 2016, a longitudinal study of youth was conducted with a baseline and 4 post-campaign follow-up surveys. The sample consisted of nonsmoking youths from 75 U.S. media markets (n=5,103) who completed a baseline and at least 1 follow-up survey. Exposure was measured by media market-level target rating points and self-reported ad exposure frequency. Smoking initiation was examined among youths who had never smoked at baseline and defined as first trial of a cigarette. Discrete-time survival models using logistic regression and controlling for confounding influences were estimated. Analyses were conducted in 2018. RESULTS: The odds of reporting smoking initiation at follow-up was lower among youths in media markets with higher levels of campaign advertisements than among those with less. Both between-wave and cumulative target rating points were associated with decreased risk of smoking initiation (AOR=0.69 [p<0.01] and AOR=0.89 [p<0.05], respectively); for every 3,500 between-wave target rating points on air, there was an associated 30% reduction in the hazard of smoking initiation among youths. Results from self-reported recall of the campaign advertisements found similar dose-response effects. The campaign is associated with an estimated 380,000-587,000 youths aged 11-19 years being prevented from initiating smoking nationwide. CONCLUSIONS: Sustained national tobacco public education campaigns like The Real Cost can change population-level smoking initiation among youths, preventing future generations from tobacco-related harms.

A patient-centred model to quality assure outputs from an echocardiography department: consensus guidance from the British Society of Echocardiography.

Background Quality assurance (QA) of echocardiographic studies is vital to ensure that clinicians can act on findings of high quality to deliver excellent patient care. To date, there is a paucity of published guidance on how to perform this QA. The British Society of Echocardiography (BSE) has previously produced an Echocardiography Quality Framework (EQF) to assist departments with their QA processes. This article expands on the EQF with a structured yet versatile approach on how to analyse echocardiographic departments to ensure high-quality standards are met. In addition, a process is detailed for departments that are seeking to demonstrate to external bodies adherence to a robust QA process. Methods The EQF consists of four domains. These include assessment of Echo Quality (including study acquisition and report generation); Reproducibility & Consistency (including analysis of individual variability when compared to the group and focused clinical audit), Education & Training (for all providers and service users) and Customer & Staff Satisfaction (of both service users and patients/their carers). Examples of what could be done in each of these areas are presented. Furthermore, evidence of participation in each domain is categorised against a red, amber or green rating: with an amber or green rating signifying that a quantifiable level of engagement in that aspect of QA has been achieved. Conclusion The proposed EQF is a powerful tool that focuses the limited time available for departmental QA on areas of practice where a change in patient experience or outcome is most likely to occur.

Cost-Effectiveness Analysis of The Real Cost Campaign's Effect on Smoking Prevention.

INTRODUCTION: A previous study found that the Food and Drug Administration's The Real Cost national tobacco education campaign was associated with preventing approximately 350,000 U.S. youth from initiating smoking between 2014 and 2016. This study translates the reduction in smoking initiation into monetary terms by examining the cost effectiveness of the campaign. METHODS: The cost effectiveness of The Real Cost was assessed by measuring efficiency in two ways: (1) estimating the cost per quality-adjusted life year saved and (2) estimating the total monetary return on investment by comparing the cost savings associated with the campaign to campaign expenditures. Analyses were conducted in 2017. RESULTS: The Real Cost averted an estimated 175,941 youth from becoming established smokers between 2014 and 2016. Campaign expenditures totaled $246,915,233. The cost per quality-adjusted life year saved of the campaign was $1,337. When considering the costs of smoking, the averted established smokers represent >$31 billion in cost savings ($1.3 billion when only external costs considered). The overall return on investment of the campaign was $128 in cost savings for every $1 spent ($4 for every $1 spent when only external costs considered). These conclusions were robust to sensitivity analyses surrounding the parameters. CONCLUSIONS: Campaign expenditures were cost efficient. The cost savings resulting from The Real Cost represent a large reduction in the financial burden to individuals, their families, and society as a result of tobacco. Public health campaigns, like The Real Cost, that reduce tobacco-related morbidity and mortality for a generation of U.S. youth also provide substantial cost savings.

Developing a Reliable Mouse Model for Cancer Therapy-Induced Cardiovascular Toxicity in Cancer Patients and Survivors.

BACKGROUND: The high incidence of cardiovascular events in cancer survivors has long been noted, but the mechanistic insights of cardiovascular toxicity of cancer treatments, especially for vessel diseases, remain unclear. It is well known that atherosclerotic plaque formation begins in the area exposed to disturbed blood flow, but the relationship between cancer therapy and disturbed flow in regulating plaque formation has not been well studied. Therefore, we had two goals for this study; (1) Generate an affordable, reliable, and reproducible mouse model to recapitulate the cancer therapy-induced cardiovascular events in cancer survivors, and (2) Establish a mouse model to investigate the interplay between disturbed flow and various cancer therapies in the process of atherosclerotic plaque formation. METHODS AND RESULTS: We examined the effects of two cancer drugs and ionizing radiation (IR) on disturbed blood flow-induced plaque formation using a mouse carotid artery partial ligation (PCL) model of atherosclerosis. We found that doxorubicin and cisplatin, which are commonly used anti-cancer drugs, had no effect on plaque formation in partially ligated carotid arteries. Similarly, PCL-induced plaque formation was not affected in mice that received IR (2 Gy) and PCL surgery performed one week later. In contrast, when PCL surgery was performed 26 days after IR treatment, not only the atherosclerotic plaque formation but also the necrotic core formation was significantly enhanced. Lastly, we found a significant increase in p90RSK phosphorylation in the plaques from the IR-treated group compared to those from the non-IR treated group. CONCLUSIONS: Our results demonstrate that IR not only increases atherosclerotic events but also vulnerable plaque formation. These increases were a somewhat delayed effect of IR as they were observed in mice with PCL surgery performed 26 days, but not 10 days, after IR exposure. A proper animal model must be developed to study how to minimize the cardiovascular toxicity due to cancer treatment.

Perceptions of the relative harmfulness of marijuana and alcohol among adults in Oregon.

This study documents perceptions of the relative harmfulness of marijuana and alcohol to a person's health among adults in Oregon just before the first legal sales of marijuana for recreational use. We surveyed 1941 adults in Oregon in September 2015. Respondents were recruited using an address-based sampling (ABS) frame (n = 1314) and social media advertising (n = 627). Respondents completed paper surveys (ABS-mail, n = 388) or online surveys (ABS-online, n = 926; social media, n = 627). We used descriptive statistics and logistic regression models to examine perceptions of the relative harmfulness of marijuana and alcohol by sample characteristics, including substance use. About half of adults in Oregon (52.5%) considered alcohol to be more harmful to a person's health than marijuana. A substantial proportion considered the substances equally harmful (40.0%). Few considered marijuana to be more harmful than alcohol (7.5%). In general, respondents who were younger, male, and not Republican were more likely than others to consider alcohol more harmful than marijuana. Respondents who were older, female, and Republican were more likely to consider marijuana and alcohol equally harmful. Most individuals who reported using both marijuana and alcohol (67.7%) and approximately half of those who used neither substance (48.2%) considered alcohol to be more harmful than marijuana. Perceptions about the relative harmfulness of marijuana and alcohol may have implications for public health. As state lawmakers develop policies to regulate marijuana, it may be helpful to consider the ways in which those policies may also affect use of alcohol and co-use of alcohol and marijuana.