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Cancer metabolism is a marvellously complex topic, in part, due to the reprogramming of its pathways to self-sustain the malignant phenotype in the disease, to the detriment of its healthy counterpart. Understanding these adjustments can provide novel targeted therapies that could disrupt and impair proliferation of cancerous cells. For this very purpose, genome-scale metabolic models (GEMs) have been developed, with Human1 being the most recent reconstruction of the human metabolism. Based on GEMs, we introduced the genetic Minimal Cut Set (gMCS) approach, an uncontextualized methodology that exploits the concepts of synthetic lethality to predict metabolic vulnerabilities in cancer. gMCSs define a set of genes whose knockout would render the cell unviable by disrupting an essential metabolic task in GEMs, thus, making cellular proliferation impossible. Here, we summarize the gMCS approach and review the current state of the methodology by performing a systematic meta-analysis based on two datasets of gene essentiality in cancer. First, we assess several thresholds and distinct methodologies for discerning highly and lowly expressed genes. Then, we address the premise that gMCSs of distinct length should have the same predictive power. Finally, we question the importance of a gene partaking in multiple gMCSs and analyze the importance of all the essential metabolic tasks defined in Human1. Our meta-analysis resulted in parameter evaluation to increase the predictive power for the gMCS approach, as well as a significant reduction of computation times by only selecting the crucial gMCS lengths, proposing the pertinency of particular parameters for the peak processing of gMCS.
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Neoplasias , Humanos , Neoplasias/genética , Proliferação de Células , Expressão Gênica , Nível de Saúde , FenótipoRESUMO
BACKGROUND: Tools for mortality prediction in patients with the severe hypercholesterolemia phenotype (low-density lipoprotein cholesterol ≥190 mg/dL) are limited and restricted to specific racial and ethnic cohorts. We sought to evaluate the predictors of long-term mortality in a large racially and ethnically diverse US patient cohort with low-density lipoprotein cholesterol ≥190 mg/dL. METHODS: We conducted a retrospective analysis of all patients with a low-density lipoprotein cholesterol ≥190 mg/dL seeking care at Montefiore from 2010 through 2020. Patients <18 years of age or with previous malignancy were excluded. The primary end point was all-cause mortality. Analyses were stratified by age, sex, and race and ethnicity. Patients were stratified by primary and secondary prevention. Cox regression analyses were used to adjust for demographic, clinical, and treatment variables. RESULTS: A total of 18 740 patients were included (37% non-Hispanic Black, 30% Hispanic, 12% non-Hispanic White, and 2% non-Hispanic Asian patients). The mean age was 53.9 years, and median follow-up was 5.2 years. Both high-density lipoprotein cholesterol and body mass index extremes were associated with higher mortality in univariate analyses. In adjusted models, higher low-density lipoprotein cholesterol and triglyceride levels were associated with an increased 9-year mortality risk (adjusted hazard ratio [HR], 1.08 [95% CI, 1.05-1.11] and 1.04 [95% CI, 1.02-1.06] per 20-mg/dL increase, respectively). Clinical factors associated with higher mortality included male sex (adjusted HR, 1.31 [95% CI, 1.08-1.58]), older age (adjusted HR, 1.19 per 5-year increase [95% CI, 1.15-1.23]), hypertension (adjusted HR, 2.01 [95% CI, 1.57-2.57]), chronic kidney disease (adjusted HR, 1.68 [95% CI, 1.36-2.09]), diabetes (adjusted HR, 1.79 [95% CI, 1.50-2.15]), heart failure (adjusted HR, 1.51 [95% CI, 1.16-1.95]), myocardial infarction (adjusted HR, 1.41 [95% CI, 1.05-1.90]), and body mass index <20 kg/m2 (adjusted HR, 3.36 [95% CI, 2.29-4.93]). A significant survival benefit was conferred by lipid-lowering therapy (adjusted HR, 0.57 [95% CI, 0.42-0.77]). In the primary prevention group, high-density lipoprotein cholesterol <40 mg/dL was independently associated with higher mortality (adjusted HR, 1.49 [95% CI, 1.06-2.09]). Temporal trend analyses showed a reduction in statin use over time (P<0.001). In the most recent time period (2019-2020), 56% of patients on primary prevention and 85% of those on secondary prevention were on statin therapy. CONCLUSIONS: In a large, diverse cohort of US patients with the severe hypercholesterolemia phenotype, we identified several patient characteristics associated with increased 9-year all-cause mortality and observed a decrease in statin use over time, in particular for primary prevention. Our results support efforts geared toward early recognition and consistent treatment for patients with severe hypercholesterolemia.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Humanos , Masculino , Pessoa de Meia-Idade , Hipercolesterolemia/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Retrospectivos , LDL-Colesterol , HDL-Colesterol , Fenótipo , Fatores de RiscoRESUMO
BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.
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Doenças das Artérias Carótidas , Estenose das Carótidas , Coinfecção , Infecções por HIV , Hepatite C , Placa Aterosclerótica , Adulto , Feminino , Humanos , Masculino , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/complicações , Estudos de Coortes , Coinfecção/diagnóstico por imagem , Coinfecção/epidemiologia , Coinfecção/complicações , Estudos Transversais , Hepacivirus , Hepatite C/complicações , Hepatite C/diagnóstico por imagem , Hepatite C/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/epidemiologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/complicações , Fatores de Risco , Pessoa de Meia-Idade , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Studies assessing equity in the prevention of atherosclerotic cardiovascular disease (ASCVD) for Latinos living in the USA collectively yield mixed results. Latino persons are diverse in many ways that may influence cardiovascular health. The intersection of Latino nativity and ASCVD prevention is understudied. OBJECTIVE: To determine whether disparities in ASCVD screening, detection, and prescribing differ for US Latinos by country of birth. DESIGN: A retrospective cohort design utilizing 2014-2020 electronic health record data from a network of 320 community health centers across 12 states. Analyses occurred October 1, 2022, to September 30, 2023. PARTICIPANTS: Non-Hispanic White and Latino adults age 20-75 years, born in Cuba, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, and the USA. EXPOSURES: Ethnicity and country of birth. MAIN MEASURES: Outcome measures included prevalence of statin eligibility, of having insufficient data to establish eligibility, odds of having a documented statin prescription, and rates of statin prescriptions and refills. We used covariate-adjusted logistic and generalized estimating equations logistic and negative binomial regressions to generate absolute and relative measures. KEY RESULTS: Among 108,672 adults, 23% (n = 25,422) were statin eligible for primary or secondary prevention of ASCVD using American College of Cardiology/American Heart Association guidelines. Latinos, born in and outside the USA were more likely eligible than Non-Hispanic White patients were (US-born Latino OR = 1.55 (95% CI = 1.37-1.75); non-US-born Latino OR = 1.63 (95% CI = 1.34-1.98)). The eligibility criteria that was met differed by ethnicity and nativity. Latinos overall were less likely missing data to establish eligibility and differences were again observed by specific non-US country of origin. Among those eligible, we observed no statistical difference in statin prescribing between US-born Latinos and non-Hispanic White persons; however, disparities varied by specific non-US country of origin. CONCLUSION: Efforts to improve Latino health in the USA will require approaches for preventing and reversing cardiovascular risk factors, and statin initiation that are Latino subgroup specific.
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Aterosclerose , Hispânico ou Latino , Prevenção Primária , Prevenção Secundária , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Hispânico ou Latino/estatística & dados numéricos , Estudos Retrospectivos , Idoso , Aterosclerose/prevenção & controle , Aterosclerose/etnologia , Prevenção Secundária/métodos , Adulto Jovem , Estados Unidos/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos de Coortes , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etnologiaRESUMO
BACKGROUND: Combat casualties are frequently injured in austere settings where modern imaging modalities are unavailable. Exploratory laparotomies are often performed in these settings when there is suspicion for intra-abdominal injury. Prior studies of combat casualties reported non-therapeutic laparotomy (NTL) rates as high as 32%. Given improvements in combat casualty care over time, we evaluated NTLs performed during later years of the wars in Iraq and Afghanistan. METHODS: Military personnel with combat-related injuries (6/1/2009-12/31/2014) who underwent exploratory laparotomy based on concern for abdominal injury (i.e. not performed for proximal vascular control or fecal diversion) and were evacuated to Landstuhl Regional Medical Center (Germany) before being transferred to participating U.S. military hospitals were assessed. An NTL was defined as a negative laparotomy without substantial intra-abdominal injuries requiring repair. Characteristics, indications for laparotomy, operative findings, and outcomes were examined. RESULTS: Among 244 patients who underwent laparotomies, 41 (16.8%) had NTLs and 203 (83.2%) had therapeutic laparotomies (i.e. positive findings). Patients with NTLs had more computed tomography scans concerning for injury (48.8% vs 27.1%; p = 0.006), less penetrating injury mechanisms (43.9% vs 71.9%; p < 0.001), and lower Injury Severity Scores (26 vs 33; p = 0.003) compared to patients with therapeutic laparotomies. Patients with NTLs were also less likely to be admitted to the intensive care unit (70.7 vs 89.2% for patients with therapeutic laparotomies; p = 0.007). No patients with NTLs developed abdominal surgical site infections (SSI) compared to 16.7% of patients with therapeutic laparotomies (p = 0.002). There was no significant difference in mortality between the groups (p = 0.198). CONCLUSIONS: Our proportion of NTLs was lower than reported from earlier years during the wars in Iraq and Afghanistan. No infectious complications from NTLs (i.e. abdominal SSIs) were identified. Nevertheless, surgeons should continue to have a low threshold for exploratory laparotomy in military patients in austere settings with concern for intra-abdominal injury.
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PURPOSE: To assess the possible benefits of the use of perceptual learning and dichoptic therapy combined with patching in children with amblyopia over the use of only patching. METHODS: Quasi-experimental multicentric study including 52 amblyopic children. Patients who improved their visual acuity (VA) by combining spectacles and patching were included in patching group (PG: 20 subjects), whereas those that did not improved with patching performed visual training (perceptual learning + dichoptic therapy) combined with patching, being assigned to the visual treatment group (VT: 32 subjects). Changes in VA, contrast sensitivity (CS), and stereopsis were monitored during a 6-month follow-up in each group. RESULTS: Significant improvements in VA were found in both groups at 1 month (p < 0.01). The total improvement of VA was 0.18 ± 0.16 and 0.31 ± 0.35 logMAR in PG and VT groups, respectively (p = 0.317). The Wilcoxon effect size was slightly higher in VT (0.48 vs. 0.54) at 6 months. An enhancement in CS was observed in the amblyopic eye of the VT group for all spatial frequencies at 1 month (p < 0.001). Likewise, the binocular function score also increased significantly in VT group (p = 0.002). A prediction equation of VA improvement at 1 month in VT group was obtained by multiple linear regression analysis (p < 0.001, R2 = 0.747). CONCLUSIONS: A combined treatment of visual training and patching is effective for obtaining a predictable improvement of VA, CS, and binocularity in patching-resistant amblyopic children.
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BACKGROUND: It is uncertain if the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines for the use of HMGCoA reductase inhibitors (statins) were associated with increased statin eligibility and prescribing across underserved groups. OBJECTIVE: To analyze, by race, ethnicity, and preferred language, patients with indications for and presence of a statin prescription before and after the guideline change. DESIGN: Retrospective cohort study. SETTING: Multistate community health center (CHC) network with linked electronic health records. PATIENTS: Low-income patients aged ≥ 50 with a primary care visit in 2009-2013 or 2014-2018. MAIN MEASURES: (1) Odds of each race/ethnicity/language group meeting statin eligibility via the National Cholesterol Education Program Adult Treatment Panel III Guidelines in 2009-2013 or the ACC/AHA guidelines in 2014-2018. (2) Among those eligible, odds of each group in each period with a statin prescription. KEY RESULTS: In 2009-2013 (n = 109,330), non-English-preferring Latino (OR = 1.10, 95% CI = 1.03, 1.17), White (OR = 1.41, 95% CI = 1.16, 1.72), and Black patients (OR = 1.25, 95% CI = 1.11, 1.42), were more likely than English-preferring non-Hispanic Whites to meet guideline criteria for statins. Non-English-preferring Black patients, when eligible, were no more likely than non-Hispanic Whites to have statin prescriptions (OR = 1.16, 95% CI = 0.88, 1.54). In 2014-2018 (n = 319,904), English-preferring Latino patients (OR = 1.02, 95% CI = 0.96-1.07) and non-English-preferring Black patients (OR = 1.08, 95% CI = 0.98, 1.19) had similar odds of statin prescription to English-preferring non-Hispanic White patients. English-preferring Black patients were less likely (OR = 0.95, 95% CI = 0.91-0.99) to have a prescription than English-preferring non-Hispanic Whites. CONCLUSION: Across the 2013 ACC/AHA guideline change in CHCs serving low-income patients, non-English-preferring patients were consistently more likely to be eligible for and have been prescribed statins. English-preferring Latino and English-preferring Black patients experienced reduced prescribing, comparatively, after the guideline change. Further work should explore the contextual factors that may influence guideline effectiveness and care equity.
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Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Adulto , Estados Unidos/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Retrospectivos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Estudos de CoortesRESUMO
BACKGROUND: Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. METHODS: We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784). RESULTS: After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. CONCLUSIONS: In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.
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Estenose da Valva Aórtica , Aterosclerose , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Estenose da Valva Aórtica/epidemiologia , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Calcinose , Proteínas de Transferência de Ésteres de Colesterol , HDL-Colesterol , Humanos , Incidência , Lipoproteínas HDL , MasculinoRESUMO
Plasmonic substrates are widely reported for their use in the manipulation of sub-wavelength particles. Here we analyze the optical force in the terahertz (THz) spectrum acting on a dielectric nanoparticle when located close to a graphene monolayer. When lying on a dielectric planar substrate, the graphene sheet enables the nano-sized scatterer to excite a surface plasmon (SP) well confined on the dielectric surface. Under quite general conditions, large pulling forces can be exerted on the particle as a consequence of conservation of linear momentum and a self-action effect. Our results show that the pulling force intensity critically depends on the particle shape and orientation. The low heat dissipation of graphene SPs paves the way for the development of a novel plasmonic tweezer for applications involving biospecimen manipulation in the THz region.
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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.
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Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adolescente , Estados Unidos/epidemiologia , Vaping/epidemiologia , Inquéritos e Questionários , Assunção de Riscos , Ideação SuicidaRESUMO
BACKGROUND: Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races. METHODS: We performed a retrospective analysis of 4 large, community cohort studies (ARIC [Atherosclerosis Risk in Communities], DHS [Dallas Heart Study], JHS [Jackson Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) with adjudicated HF events. The study included participants who were >40 years of age and free of HF at baseline. Race-specific ML models for HF risk prediction were developed in the JHS cohort (for Black race-specific model) and White adults from ARIC (for White race-specific model). The models included 39 candidate variables across demographic, anthropometric, medical history, laboratory, and electrocardiographic domains. The ML models were externally validated and compared with prior established traditional and non-race-specific ML models in race-specific subgroups of the pooled MESA/DHS cohort and Black participants of ARIC. The Harrell C-index and Greenwood-Nam-D'Agostino χ2 tests were used to assess discrimination and calibration, respectively. RESULTS: The ML models had excellent discrimination in the derivation cohorts for Black (n=4141 in JHS, C-index=0.88) and White (n=7858 in ARIC, C-index=0.89) participants. In the external validation cohorts, the race-specific ML model demonstrated adequate calibration and superior discrimination (Black individuals, C-index=0.80-0.83; White individuals, C-index=0.82) compared with established HF risk models or with non-race-specific ML models derived with race included as a covariate. Among the risk factors, natriuretic peptide levels were the most important predictor of HF risk across both races, followed by troponin levels in Black and ECG-based Cornell voltage in White individuals. Other key predictors of HF risk among Black individuals were glycemic parameters and socioeconomic factors. In contrast, prevalent cardiovascular disease and traditional cardiovascular risk factors were stronger predictors of HF risk in White adults. CONCLUSIONS: Race-specific and ML-based HF risk models that integrate clinical, laboratory, and biomarker data demonstrated superior performance compared with traditional HF risk and non-race-specific ML models. This approach identifies distinct race-specific contributors of HF.
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Insuficiência Cardíaca/diagnóstico , Aprendizado de Máquina , Idoso , População Negra , Estudos de Coortes , Eletrocardiografia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Raciais , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Troponina I/sangue , População BrancaRESUMO
Manipulation of nano-scale objects by engineering the electromagnetic waves in the environment medium is pivotal for several particle handling techniques using optical resonators, waveguiding, and plasmonic devices. In this Letter, we theoretically demonstrate the possibility of engineering a compact and tunable plasmon-based terahertz (THz) tweezer using a graphene monolayer that is deposited on a high-index dielectric substrate. When a nanoparticle located in a vacuum in the vicinity of the graphene monolayer is illuminated under total internal reflection, as light is launched from the substrate, such a device is shown to be capable of inducing an enhanced rotating dipole in the nanoparticle thus enabling asymmetric, directional near-field coupling into the graphene plasmon mode and the radiative modes in the substrate. As a result of the total momentum conservation, the net force exerted on the particle points in a direction opposite to the pushing scattering force of the exciting evanescent field. Our results can contribute to novel realizations of photonic devices based on polarization-dependent interactions between nanoparticles and electromagnetic mode fields.
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Objective: Atheromatous fibrous caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We tested whether the recruitment mechanisms are the same as in embryonic artery development, which relies prominently on Notch signaling to form the subendothelial medial SMC layers. Approach and Results: Notch elements were expressed in regions of fibrous cap in human and mouse plaques. To assess the causal role of Notch signaling in cap formation, we studied atherosclerosis in mice where the Notch pathway was inactivated in SMCs by conditional knockout of the essential effector transcription factor RBPJ (recombination signal-binding protein for immunoglobulin kappa J region). The recruitment of cap SMCs was significantly reduced without major effects on plaque size. Lineage tracing revealed the accumulation of SMC-derived plaque cells in the cap region was unaltered but that Notch-defective cells failed to re-acquire the SMC phenotype in the cap. Conversely, to analyze whether the loss of Notch signaling is required for SMC-derived cells to accumulate in atherogenesis, we studied atherosclerosis in mice with constitutive activation of Notch signaling in SMCs achieved by conditional expression of the Notch intracellular domain. Forced Notch signaling inhibited the ability of medial SMCs to contribute to plaque cells, including both cap SMCs and osteochondrogenic cells, and significantly reduced atherosclerosis development. Conclusions: Sequential loss and gain of Notch signaling is needed to build the cap SMC population. The shared mechanisms with embryonic arterial media assembly suggest that the cap forms as a neo-media that restores the connection between endothelium and subendothelial SMCs, transiently disrupted in early atherogenesis.
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Aterosclerose/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica , Receptores Notch/metabolismo , Túnica Média/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Artérias/metabolismo , Artérias/patologia , Aterosclerose/genética , Aterosclerose/patologia , Linhagem da Célula , Células Cultivadas , Progressão da Doença , Fibrose , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fenótipo , Ratos , Receptores Notch/genética , Transdução de Sinais , Túnica Média/patologiaRESUMO
Atherosclerotic cardiovascular disease (ASCVD) disproportionally affects racial and ethnic minority populations. Statin prescribing guidelines changed in 2013 to improve ASCVD prevention. It is unknown whether risk screening for statin eligibility differed across race and ethnicity over this guideline change. We examine racial/ethnic/language differences in screening measure prevalence for period-specific statin consideration using a retrospective cohort design and linked electronic health records from 635 community health centers in 24 U.S. states. Adults 50+ years, without known ASCVD, and ≥ 1 visit in 2009-2013 and/or 2014-2018 were included, grouped as: Asian, Latino, Black, or White further distinguished by language preference. Outcomes included screening measure prevalence for statin consideration, 2009-2013: low-density lipoprotein (LDL), 2014-2018: pooled cohort equation (PCE) components age, sex, race, systolic blood pressure, total cholesterol, high-density lipoprotein, smoking status. Among patients seen both periods, change in period-specific measure prevalence was assessed. Adjusting for sociodemographic and clinical factors, compared to English-preferring White patients, all other groups were more likely to have LDL documented (2009-2013, n = 195,061) and all PCE components documented (2014-2018, n = 344,504). Among patients seen in both periods (n = 128,621), all groups had lower odds of PCE components versus LDL documented in the measures' respective period; English-preferring Black adults experienced a greater decline compared to English-preferring White adults (OR 0.81; 95% CI: 0.72-0.91). Racial/ethnic/language disparities in documented screening measures that guide statin therapy for ASCVD prevention were unaffected by a major guideline change advising this practice. It is important to understand whether the newer guidelines have altered disparate prescribing and morbidity/mortality for this disease.
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Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Adulto , Humanos , Etnicidade , Idioma , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Grupos Minoritários , Estudos Retrospectivos , Aterosclerose/prevenção & controleRESUMO
OBJECTIVE: The aim of this study was to examine perceptions including knowledge, attitudes, and beliefs about e-cigarettes among ethno-culturally diverse Latino adults living in the US, a rapidly growing minority group for which we know little about their e-cigarette perceptions. DESIGN: A total of 25 focus groups with Latinos (n = 180; ages 18-64 years) were conducted in 2014. E-cigarettes users and non-users were recruited via purposive sampling techniques. Participants completed brief questionnaires on sociodemographic factors and tobacco use. Focus group discussions were conducted in English and Spanish, audio-recorded, and transcribed. Data were analyzed using thematic analysis procedures. RESULTS: Participants were of diverse Latino backgrounds. Over one-third (35%) reported current cigarette smoking and 8% reported current e-cigarette or hookah use. Nonsmokers reported experimenting with e-cigarettes and hookah during social occasions. Participants' perceptions towards e-cigarettes were generally formed in comparison to conventional cigarettes. Perceived benefits of using e-cigarettes included their utility as a smoking cessation aid, higher social acceptability, and lower harm compared to conventional cigarettes. Negative perceptions of e-cigarettes included lower overall satisfaction compared to conventional cigarettes and high content of toxins. Socio-cultural factors (e.g. gender roles, familismo, and simpatía) also influenced perceptions of e-cigarette of study participants. CONCLUSIONS: Overall, Latino adults knew relatively little about the potential health risks associated with e-cigarette use. The limited knowledge about and misinformation of e-cigarettes among this rapidly growing minority group have important public health implications. Findings may inform culturally tailored health communication campaigns, which are much needed among underserved US Latino populations in light of low effectiveness of tobacco control and regulatory efforts.
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Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Vaping , Adolescente , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Hispânico ou Latino , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
The mission of the American Heart Association is to be a relentless force for a world of longer, healthier lives. The American Heart Association has consistently prioritized the needs and perspective of the patient in taking positions on healthcare reform while recognizing the importance of biomedical research, providers, and healthcare delivery systems in advancing the care of patients and the prevention of disease. The American Heart Association's vision for healthcare reform describes the foundational changes needed for the health system to serve the best interests of patients and to achieve health care and coverage that are adequate, accessible, and affordable for everyone living in the United States. The American Heart Association is committed to advancing the dialogue around healthcare reform and has prepared this updated statement of our principles, placed in the context of the advances in coverage and care that have occurred after the passage of the Affordable Care Act, the rapidly changing landscape of healthcare delivery systems, and our evolving recognition that efforts to prevent cardiovascular disease can have synergistic benefit in preventing other diseases and improving overall well-being. These updated principles focus on expanding access to affordable health care and coverage; enhancing the availability of evidence-based preventive services; eliminating disparities that limit the availability and equitable delivery of health care; strengthening the public health infrastructure to respond to social determinants of health; prioritizing and accelerating investments in biomedical research; and growing a diverse, culturally competent health and healthcare workforce prepared to meet the challenges of delivering high-value health care.
Assuntos
Doenças Cardiovasculares/epidemiologia , Reforma dos Serviços de Saúde , Acessibilidade aos Serviços de Saúde/normas , American Heart Association , Custos e Análise de Custo , Atenção à Saúde , Humanos , Serviços Preventivos de Saúde , Melhoria de Qualidade , Estados Unidos/epidemiologiaRESUMO
Structural racism has been and remains a fundamental cause of persistent health disparities in the United States. The coronavirus disease 2019 (COVID-19) pandemic and the police killings of George Floyd, Breonna Taylor, and multiple others have been reminders that structural racism persists and restricts the opportunities for long, healthy lives of Black Americans and other historically disenfranchised groups. The American Heart Association has previously published statements addressing cardiovascular and cerebrovascular risk and disparities among racial and ethnic groups in the United States, but these statements have not adequately recognized structural racism as a fundamental cause of poor health and disparities in cardiovascular disease. This presidential advisory reviews the historical context, current state, and potential solutions to address structural racism in our country. Several principles emerge from our review: racism persists; racism is experienced; and the task of dismantling racism must belong to all of society. It cannot be accomplished by affected individuals alone. The path forward requires our commitment to transforming the conditions of historically marginalized communities, improving the quality of housing and neighborhood environments of these populations, advocating for policies that eliminate inequities in access to economic opportunities, quality education, and health care, and enhancing allyship among racial and ethnic groups. Future research on racism must be accelerated and should investigate the joint effects of multiple domains of racism (structural, interpersonal, cultural, anti-Black). The American Heart Association must look internally to correct its own shortcomings and advance antiracist policies and practices regarding science, public and professional education, and advocacy. With this advisory, the American Heart Association declares its unequivocal support of antiracist principles.
Assuntos
American Heart Association , Disparidades em Assistência à Saúde , Racismo , Acidente Vascular Cerebral/terapia , Atenção à Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Humanos , Qualidade da Assistência à Saúde , Estados UnidosRESUMO
The ability to control the laser modes within a subwavelength resonator is of key relevance in modern optoelectronics. This work deals with the theoretical research on optical properties of a PT-symmetric nano-scaled dimer formed by two dielectric wires, one is with loss and the other with gain, wrapped with graphene sheets. We show the existence of two non-radiating trapped modes which transform into radiating modes by increasing the gain-loss parameter. Moreover, these modes reach the lasing condition for suitable values of this parameter, a fact that makes these modes achieve an ultra high quality factor that is manifested on the response of the structure when it is excited by a plane wave. Unlike other mechanisms that transform trapped modes into radiating modes, we show that the variation of gain-loss parameter in the balanced loss-gain structure here studied leads to a variation in the phase difference between induced dipole moments on each wires, without appreciable variation in the modulus of these dipole moments. We provide an approximated method that reproduces the main results provided by the rigorous calculation. Our theoretical findings reveal the possibility to develop unconventional optical devices and structures with enhanced functionality.
RESUMO
OBJECTIVE: Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos. METHODS: Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders. RESULTS: In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02). CONCLUSIONS: It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.
Assuntos
Colesterol/sangue , Cognição/fisiologia , Disfunção Cognitiva , Dislipidemias , Hispânico ou Latino/estatística & dados numéricos , Triglicerídeos/sangue , Idoso , Biomarcadores/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etnologia , Disfunção Cognitiva/fisiopatologia , Dislipidemias/sangue , Dislipidemias/etnologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Fatores de Risco , Estados Unidos/etnologiaRESUMO
This study evaluated the characteristics of suicide news articles in the digital press, their adherence to World Health Organization (WHO) recommendations, and the effectiveness of interventions. We assessed adherence, avoidability, frequency and typology of suicide news over a six-month period in the four main digital media outlets of the Canary Islands (Spain). A brief training and information package intervention to the Canary Islands media outlets was carried out. We compared the quality of media reporting at both the pre-intervention and post-intervention timepoints, and compared the quality of reporting at the post-intervention timepoint in Victoria (Australia), where media interventions have been well-resourced and running for several years. We evaluated 339 suicide news articles: 38 from the pre-intervention period, 64 from the post-intervention period, and 237 from Victoria. News articles showed a very low degree of adherence to WHO recommendations, especially to those recommendations thought to have a protective effect. Post-intervention news articles showed better adherence than pre-intervention ones, but lower than those of Victoria, where constant interventions have been developed for years. We conclude that adherence to WHO recommendations is low. Simple interventions aimed at media professionals can improve adherence. However, constant and complex interventions seem to be more effective.