Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. METHODS: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. RESULTS: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Coronary artery calcium testing in young adults.

PURPOSE OF REVIEW: To provide a summary of recent literature on coronary artery calcium testing (CAC) for risk stratification in young adults <45 years old. RECENT FINDINGS: One of every ten young adults in the general population, and one out of every three young adults with traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, have CAC. While the definition of premature CAC has yet to be formally defined in guidelines, it has become increasingly clear that any prevalent CAC among adults <45 years old should be considered premature. Traditional risk factors are strong predictors of CAC in young adults; however, this association has been found to wane over the life course which suggests that the onset and severity of risk factors for calcific atherosclerosis varies as individuals age. Though CAC is a robust predictor of both ASCVD and cancer-related mortality in old age, CAC in young adults confers a stepwise higher risk uniquely for incident ASCVD mortality, and not for non-ASCVD causes. New tools are available to assist in interpretation of CAC in the young, and for estimating the ideal age to initiate CAC scoring. SUMMARY: The identification of premature CAC is important because it suggests that calcific plaque can be detected with modern imaging earlier in the natural history than previously thought. Taken together, these findings underline a utility of selective use of CAC scoring on non-contrast computed tomography among at-risk young adults to facilitate timely lifestyle modification and pharmacotherapies for the prevention of later life ASCVD.

Coronary artery calcium and sudden cardiac death: current evidence and future directions.

PURPOSE OF REVIEW: To provide a summary of the current evidence and highlight future directions regarding coronary artery calcium (CAC) and risk of sudden cardiac death (SCD). RECENT FINDINGS: Although up to 80% of all SCD is attributed to coronary heart disease (CHD), the subclinical atherosclerosis markers that help to improve SCD risk prediction are largely unknown. Recent observational data have demonstrated that, after adjustment for traditional risk factors, there is a stepwise higher risk for SCD across increasing CAC burden such that asymptomatic patients without overt atherosclerotic cardiovascular disease (ASCVD) experience a three-fold to five-fold higher SCD risk beginning at CAC at least 100 when compared with CAC = 0. Although the mechanisms underlying increasing CAC and SCD risk have yet to be fully elucidated, risk for myocardial infarction and scar, and/or exercise-induced ischemia may be potential mediators. SUMMARY: High CAC burden is an important risk factor for SCD in asymptomatic middle-aged adults, suggesting that SCD risk stratification can begin in the early stages of CHD via measurement of calcific plaque on noncontrast computed tomography. Despite the clinical inertia for downstream functional cardiac testing after detecting high CAC, comprehensive ASCVD prevention strategies should be the primary focus for SCD risk reduction.

Psychosocial stressors and current e-cigarette use in the youth risk behavior survey.

BACKGROUND: This study explores the association between psychosocial stressors and current e-cigarette use among adolescents in the United States. METHODS: We used data from 12,767 participants in the 2019 National Youth Risk Behavioral Survey to examine the association between psychosocial stressors (bullying, sexual assault, safety-related absence from school, depressive symptoms, suicidal ideation, physical altercation, and weapon threats) and past-30-day e-cigarette use using multivariable-adjusted logistic regression models. We examined the association for each stressor and then as a burden score (0-7). To compare the strength of the association between stressors and current e-cigarette use to current combustible cigarette use, we additionally examined the association between each stressor and current combustible cigarette use. RESULTS: Approximately 32.7% reported current e-cigarette use. The weighted prevalence of current e-cigarette use was higher among individuals who experienced stressors than those who did not. For example, bullying (43.9% vs. 29.0%). Similar prevalence patterns were seen among other stressors. Individuals who experienced stressors had significantly higher adjusted odds of current e-cigarette use than those who did not (OR [Odds Ratio] range: 1.47-1.75). Similarly, individuals with higher burden scores had a higher prevalence (zero [20.5%], one [32.8%], two [41.4%], three [49.6%], four to seven [60.9%]) and higher odds of current e-cigarette use (OR range: 1.43-2.73) than those with a score of zero. The strength of the association between the stressors and e-cigarette use was similar to that between the stressors and combustible cigarette use. CONCLUSION: The study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

BACKGROUND: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. METHODS: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). RESULTS: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. CONCLUSIONS: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Impact of the Food and Drug Administration enforcement policy on flavored e-cigarettes on the online popularity of disposable e-cigarettes: analyses of Google search query data.

BACKGROUND: The impact of the U.S. Food and Drug Administration's (FDA) initial enforcement policy on flavored cartridge-based e-cigarettes and subsequent notice for the removal of flavored disposable electronic cigarettes (e-cigarettes) such as Puff Bar from the market has not been well evaluated. We, therefore, sought to examine the impact of the e-cigarette flavor-related policy changes on the online popularity of Puff Bar, a prototypic disposable e-cigarette. METHODS: We tabulated the total weekly Google search queries originating from the U.S. for "Puff Bar" and "Puff Bars" from January 1, 2019, to December 31, 2021. We divided the three years into four (4) distinct periods using the dates of the initial announcement to ban non-tobacco flavored e-cigarettes (September 11, 2019), the finalization of the FDA enforcement policy on cartridge-based flavors (January 2, 2020), and the notice for the market withdrawal of flavored disposable e-cigarettes (July 20, 2020) as reference time points. Then, we used piecewise linear regression and autoregressive integrated moving average (ARIMA) to compare the trends in searches for Puff Bar for the four (4) periods. RESULTS: Before the initial announcement to ban non-tobacco flavored e-cigarettes, online search queries (per 10 million Google searches) for Puff Bar were slowly rising at a rate of 0.58 queries per week (95%CI: -0.80 - 1.97). Following the announcement, searches for Puff Bar increased significantly at a rate of 16.61 queries per week (95%CI: 12.13 - 21.10). The rate of searches for Puff Bar then increased exponentially at 40.08 queries per week (95%CI: 27.32 - 52.84) following the FDA flavor ban, which excluded disposable e-cigarettes. Then, the rate of increase declined but remained relatively stable at 3.67 queries per week (95%CI: 0.69-6.65) until the FDA's notice to remove flavored Puff Bar products from the market. Following this notice, the rate of searches for Puff Bar significantly declined (rate: -4.97 queries per week; 95%CI: -5.40--4.54). CONCLUSIONS: The tracking of online search data demonstrates rapid public recognition of the FDA's announcements of tobacco regulatory actions.

Synergistic Toll-like Receptor 3/9 Signaling Affects Properties and Impairs Glioma-Promoting Activity of Microglia.

In murine experimental glioma models, TLR3 or TLR9 activation of microglial/macrophages has been shown to impair glioma growth, which could, however, not been verified in recent clinical trials. We therefore tested whether combined TLR3 and TLR9 activation of microglia/macrophages would have a synergistic effect. Indeed, combined TLR3/TLR9 activation augmented the suppression of glioma growth in organotypic brain slices from male mice in a microglia-dependent fashion, and this synergistic suppression depended on interferon ß release and phagocytic tumor clearance. Combined TLR3/TLR9 stimulation also augmented several functional features of microglia, such as the release of proinflammatory factors, motility, and phagocytosis activity. TLR3/TLR9 stimulation combined with CD47 blockade further augmented glioma clearance. Finally, we confirmed that the coactivation of TLR3/TLR9 also augments the impairment of glioma growth in vivo Our results show that combined activation of TLR3/TLR9 in microglia/macrophages results in a more efficient glioma suppression, which may provide a potential strategy for glioma treatment.SIGNIFICANCE STATEMENT Glioma-associated microglia/macrophages (GAMs) are the predominant immune cells in glioma growth and are recently considered as antitumor targets. TLRs are involved in glioma growth, but the TLR3 or TLR9 ligands were not successful in clinical trials in treating glioma. We therefore combined TLR3 and TLR9 activation of GAMs, resulting in a strong synergistic effect of tumor clearance in vitro, ex vivo, and in vivo Mechanisms of this GAM-glioma interaction involve IFNß signaling and increased tumor clearance by GAMs. Interfering with CD47 signaling had an additional impact on tumor clearance. We propose that these signaling pathways could be exploited as anti-glioma targets.

Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. METHODS: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT5) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH5) estimations. RESULTS: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH5 was 355. The NNT5 was also greater than or similar to the NNH5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT5 was lower than NNH5. This was true both overall (for CAC≥100, NNT5=140 versus NNH5=518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT5 was much higher than the NNH5 (overall, NNT5=1190 versus NNH5=567). CONCLUSIONS: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Fitness and prostate cancer screening, incidence, and mortality: Results from the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality. METHODS: The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (<6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models. RESULTS: In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (<6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged <55 years, P = .02; men aged >55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9). CONCLUSIONS: Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.

Glial cell line-derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia-mediated glioma progression.

Glial cell line-derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF-induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen-activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll-like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro-tumorigenic phenotype of microglia.

Decreased public pursuit of cancer-related information during the COVID-19 pandemic in the United States.

BACKGROUND: In response to the prioritization of healthcare resources towards the COVID-19 pandemic, routine cancer screening and diagnostic have been disrupted, potentially explaining the apparent COVID-era decline in cancer cases and mortality. In this study, we identified temporal trends in public interest in cancer-related health information using the nowcasting tool Google Trends. METHODS: We used Google Trends to query search terms related to cancer types for short-term (September 2019-September 2020) and long-term (September 2016-September 2020) trends in the US. We compared average relative search volumes (RSV) for specified time ranges to detect recent and seasonal variation. RESULTS: General search interest declined for all cancer types beginning in March 2020, with changes in search interest for "Breast cancer," "Colorectal cancer," and "Melanoma" of - 30.6%, - 28.2%, and - 26.7%, respectively, and compared with the mean RSV of the two previous months. In the same time range, search interest for "Telemedicine" has increased by + 907.1% and has reached a 4-year peak with a sustained increased level of search interest. Absolute cancer mortality has declined and is presently at a 4-year low; however, search interest in cancer has been recuperating since July 2020. CONCLUSION: We observed a marked decline in searches for cancer-related health information that mirrors the reduction in new cancer diagnoses and cancer mortality during the COVID-19 pandemic. Health professions need to be prepared for the coming demand for cancer-related healthcare, foreshadowed by recovering interest in cancer-related information on Google Trends.

Evaluation of coronary stenosis versus plaque burden for atherosclerotic cardiovascular disease risk assessment and management.

PURPOSE OF REVIEW: To provide a summary of recent literature on the relative impact of luminal stenosis versus atherosclerotic plaque burden in atherosclerotic cardiovascular disease (ASCVD) risk stratification and management. RECENT FINDINGS: Recent results from both randomized controlled clinical trials as well as observational cohort studies have demonstrated that ASCVD risk is mediated mainly by the extent of atherosclerotic disease burden rather than by the presence of coronary stenosis or inducible ischemia. Although patients with obstructive CAD are generally at higher risk for ASCVD events than patients with nonobstructive CAD, this is driven by a higher plaque burden in those with obstructive CAD. Accordingly, the ASCVD risk for a given plaque burden is similar in patients with and without obstructive CAD. Accompanying these observations are randomized controlled trial data, which show that optimization of medical therapy instead of early revascularization is most important for improving prognosis in patients with stable obstructive CAD. SUMMARY: Emerging evidence shows that atherosclerotic plaque burden, and not stenosis per se, is the main driver of ASCVD risk in patients with CAD. This information challenges the current paradigm of selecting patients for intensive secondary prevention measures based primarily on the presence of obstructive CAD.

Internet Search Trends Relevant to Interventional Oncology: A Google Trends Study (2004-2020).

Interventional Radiology (IR) procedures addressing cancer have been grouped in the subspecialty of interventional oncology and represent an important component of modern multidisciplinary cancer care. This study pinpoints temporal and geographical trends of public online searches for terms related to the field, as well as IR-related cancer therapies. Google Trends data were analyzed for long-term (2004-2020) trends in the United States and worldwide. Overall, search interest for IR increased throughout the United States but decreased globally. Specific search volumes for cancer-related IR techniques such as radioembolization and chemoembolization therapies increased by 2.8- and 2.5-fold, respectively, in the United States, whereas the search volumes for ablation techniques remained steady or decreased. Future research and advocacy may focus on increasing public awareness of the field.

Cannabis vaping among adults in the United States: Prevalence, trends, and association with high-risk behaviors and adverse respiratory conditions.

The e-cigarette or vaping product-use-associated lung injury outbreak in the United States has raised concerns about the potential health effects of cannabis vaping, a method of cannabis use that is becoming increasingly popular. We used 2017-2019 Behavioral Risk Factor Surveillance System data to estimate yearly prevalence and trends of past-30-day cannabis use and vaping among US adults. We used multivariable logistic regression to evaluate the associations of cannabis vaping with high-risk behaviors, asthma, and other respiratory symptoms. Our sample size was 160,209 (53,945-2017; 55,475-2018; and 50,789-2019). Past-30-day cannabis use prevalence increased from 10.0% (95% CI, 9.4%-10.7%) in 2017 to 13.4% (12.8%-12.0%) in 2019. Similarly, past-30-day cannabis vaping prevalence increased from 1.0% (0.8%-1.2%) to 2.0% (1.7%-2.2%) over the same period, with the greatest increase, 1.2% to 3.9%, observed among young adults (18-24 years). Individuals who vaped cannabis were more likely to concurrently vape nicotine. Cannabis vaping was associated with increased odds of heavy alcohol use (aOR, 1.95; 95% CI, 1.45-2.63), binge drinking (aOR, 2.82; 95% CI, 2.25-3.54), and other high-risk behaviors (aOR, 2.47; 95% CI, 1.89-3.24). In analyses adjusting for sociodemographic characteristics and body mass index, cannabis vaping was not associated with asthma (aOR, 1.03; 95% CI, 0.64-1.64) or other respiratory symptoms (aOR, 1.08; 95% CI, 0.44-2.63). Adjusting for nicotine vaping did not substantively alter these associations. The prevalence of past-30-day cannabis vaping has increased, particularly among young adults, and was associated with high-risk behaviors. Although there was no association between cannabis vaping and asthma or other respiratory symptoms, the increasing trends of cannabis vaping, particularly among young adults, raise concern and underscore the need for continued surveillance.

Down-regulation of Aquaporin-1 mediates a microglial phenotype switch affecting glioma growth.

Aquaporin 1 (AQP1), a transmembrane protein that forms water channels, has previously been shown to facilitate growth and progression of many types of tumors by modulating tumor cell migration, proliferation and angiogenesis. Here, we determined the impact of AQP1 expression in the tumor environment on the progression of brain tumors. Primary microglia from wild type(WT) and AQP1 knockout(KO) mice were used to test AQP1 effect on microglia function by using Western blot, quantative PCR, in an experimental in vivo mouse glioma model and organotypic brain slice culture. Deletion of AQP1 in the host tissue significantly reduced the survival of the mice implanted with GL261 glioma cells. The density of glioma-associated microglia/macrophages was almost doubled in AQP1KO mice. We found that factors secreted from GL261 cells decrease microglial AQP1 expression via the MEK/ERK pathway, and that inhibition of this pathway with Trametinib reduced tumor growth and prolonged the survival of tumor bearing mice, an effect which required the presence of microglia. Deletion of AQP1 in cultured microglia resulted in an increase in migratory activity and a decrease in TLR4-dependent innate immune responses. Our study demonstrates a functional relevance of AQP1 expression in microglia and hints to AQP1 as a potential novel target for glioma therapy.

Understanding myocardial infarction trends during the early COVID-19 pandemic: an infodemiology study.

During the first months of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, Google Trends data in the United States showed a strong increase in search query frequency for chest pain symptoms despite a concurrent decrease in search interest for myocardial infarction. This suggests a reduced attention to acute coronary syndrome (ACS) and chest pain as its main symptom during this time period. These observations could help explain why cardiovascular mortality rose dramatically despite a strong decrease in hospitalisation rates for ACS.

Comprehensive Care Models for Cardiometabolic Disease.

PURPOSE OF REVIEW: The high burden of cardiovascular disease and the simultaneous obesity pandemic is placing an extraordinary strain on the health care system. In the current siloed care model, patients with cardiometabolic disease receive only fractionated care from multiple specialists, leading to insufficient treatment, higher costs, and worse outcomes. RECENT FINDINGS: The imminent need for a new care model calls for the creation of a distinct cardiometabolic specialty in conjunction with a cardiometabolic outpatient clinic dedicated to the comprehensive cardiometabolic care. The cardiometabolic clinic would consist of a diverse range of professionals relevant to comprehensive treatment. The outpatient clinic we envision here would facilitate an interdisciplinary collaboration between specialists and deliver prevention-focused treatment to patients at risk/established cardiometabolic disease.

Prevalence, Trends, and Distribution of Nicotine and Marijuana use in E-cigarettes among US adults: The Behavioral Risk Factor Surveillance System 2016-2018.

Use of substances other than nicotine in e-cigarettes, especially marijuana, is becoming increasingly popular in the US. However, population-representative data on such poly-use (nicotine and marijuana) remains limited. We therefore conducted a cross-sectional logistic regression analysis of the 2018 Behavioral Risk Factor Surveillance System among 16 US states/territories with data on past 30-day marijuana use to describe the emerging dual nicotine and marijuana vaping population. We additionally examined trends in marijuana use, including marijuana vaping, from 2016 to 2018. Of the 131,807 participants studied, 3068 were current e-cigarette users, among whom 7.1% also vaped marijuana. Prevalence of nicotine-predominant, dual nicotine marijuana, and marijuana-predominant vaping was 3.36%, 0.38% and 1.09%, respectively. Compared to nicotine-predominant vapers, dual and marijuana-predominant vapers were older, had greater proportions of non-Whites, particularly Hispanics, and less likely to be current smokers (nicotine-predominant vs dual vs marijuana-predominant vaping: current tobacco use 44.7 vs 23.7 vs 11.1%). Proportion of dual vapers among current e-cigarette users was 8.6%, 2.6% and 7.1% for 2016, 2017 and 2018, respectively. Prevalence of marijuana use increased from 8.97% (2016) to 13.1% (2018) while no clear trend was observed for marijuana vaping. Dual nicotine and marijuana vaping is prevalent in the US, and compared to predominantly nicotine vapers such users have higher mean ages, and are more likely to be Blacks, Hispanics, and never cigarette smokers. Marijuana use overall increased from 2016 to 2018. Dual vapers represent a large and important emerging population that will require dedicated study of health effects and tailored regulatory strategies.

Tenascin-C Function in Glioma: Immunomodulation and Beyond.

First identified in the 1980s, tenascin-C (TNC) is a multi-domain extracellular matrix glycoprotein abundantly expressed during the development of multicellular organisms. TNC level is undetectable in most adult tissues but rapidly and transiently induced by a handful of pro-inflammatory cytokines in a variety of pathological conditions including infection, inflammation, fibrosis, and wound healing. Persistent TNC expression is associated with chronic inflammation and many malignancies, including glioma. By interacting with its receptor integrin and a myriad of other binding partners, TNC elicits context- and cell type-dependent function to regulate cell adhesion, migration, proliferation, and angiogenesis. TNC operates as an endogenous activator of toll-like receptor 4 and promotes inflammatory response by inducing the expression of multiple pro-inflammatory factors in innate immune cells such as microglia and macrophages. In addition, TNC drives macrophage differentiation and polarization predominantly towards an M1-like phenotype. In contrast, TNC shows immunosuppressive function in T cells. In glioma, TNC is expressed by tumor cells and stromal cells; high expression of TNC is correlated with tumor progression and poor prognosis. Besides promoting glioma invasion and angiogenesis, TNC has been found to affect the morphology and function of tumor-associated microglia/macrophages in glioma. Clinically, TNC can serve as a biomarker for tumor progression; and TNC antibodies have been utilized as an adjuvant agent to deliver anti-tumor drugs to target glioma. A better mechanistic understanding of how TNC impacts innate and adaptive immunity during tumorigenesis and tumor progression will open new therapeutic avenues to treat brain tumors and other malignancies.

The Promise and Peril of Vaping.

PURPOSE OF REVIEW: The increasing popularity and prevalence of electronic cigarettes (e-cigarettes) use in the USA necessitates careful evaluation of their proposed benefits and potential public health harms. This report provides a detailed review of current scientific evidence on potential benefits and health risks associated with e-cigarette use. RECENT FINDINGS: E-cigarettes were introduced as a less harmful alternative to combustible cigarette smoking. However, evidence on their use as effective and safe smoking cessation aids remains inconclusive. Their rapid uptake among tobacco-naive individuals can lead to nicotine addiction and subsequent cigarette smoking. Although e-cigarettes appear to be relatively safer than combustible cigarettes, they expose users to known harmful constituents whose long-term health risks remain unknown. While e-cigarettes have the potential to aid in cessation of cigarette smoking when used as part of a structured cessation program, use among tobacco-naive youth and long-term dual use with combustible cigarettes should be strongly discouraged due to excess risk with dual use.