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1.
Cell ; 179(5): 1084-1097.e21, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31730851

RESUMO

The ocean is home to myriad small planktonic organisms that underpin the functioning of marine ecosystems. However, their spatial patterns of diversity and the underlying drivers remain poorly known, precluding projections of their responses to global changes. Here we investigate the latitudinal gradients and global predictors of plankton diversity across archaea, bacteria, eukaryotes, and major virus clades using both molecular and imaging data from Tara Oceans. We show a decline of diversity for most planktonic groups toward the poles, mainly driven by decreasing ocean temperatures. Projections into the future suggest that severe warming of the surface ocean by the end of the 21st century could lead to tropicalization of the diversity of most planktonic groups in temperate and polar regions. These changes may have multiple consequences for marine ecosystem functioning and services and are expected to be particularly significant in key areas for carbon sequestration, fisheries, and marine conservation. VIDEO ABSTRACT.


Assuntos
Biodiversidade , Plâncton/fisiologia , Água do Mar/microbiologia , Geografia , Modelos Teóricos , Oceanos e Mares , Filogenia
2.
Trends Biochem Sci ; 49(6): 471-474, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38514275

RESUMO

Discoveries at the frontiers of science and finding solutions to pressing biomedical problems will be accelerated when talent, which is widely distributed, is better aligned with opportunities. Strategies to enhance a MOSAIC (Maximizing Opportunities for Scientific and Academic Independent Careers) professoriate and diversify the biomedical landscape are discussed.


Assuntos
Ciência , Humanos , Pesquisa Biomédica , Escolha da Profissão
3.
Annu Rev Genet ; 54: 511-537, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-32926793

RESUMO

Tuberculosis claims more human lives than any other bacterial infectious disease and represents a clear and present danger to global health as new tools for vaccination, treatment, and interruption of transmission have been slow to emerge. Additionally, tuberculosis presents with notable clinical heterogeneity, which complicates diagnosis, treatment, and the establishment of nonrelapsing cure. How this heterogeneity is driven by the diversity ofclinical isolates of the causative agent, Mycobacterium tuberculosis, has recently garnered attention. Herein, we review advances in the understanding of how naturally occurring variation in clinical isolates affects transmissibility, pathogenesis, immune modulation, and drug resistance. We also summarize how specific changes in transcriptional responses can modulate infection or disease outcome, together with strain-specific effects on gene essentiality. Further understanding of how this diversity of M. tuberculosis isolates affects disease and treatment outcomes will enable the development of more effective therapeutic options and vaccines for this dreaded disease.


Assuntos
Variação Genética/genética , Mycobacterium tuberculosis/genética , Animais , Genótipo , Humanos , Transcrição Gênica/genética , Tuberculose/microbiologia
4.
Proc Natl Acad Sci U S A ; 121(38): e2319341121, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39259592

RESUMO

Here we announce the construction and properties of a big commutative subalgebra of the Kirillov algebra attached to a finite dimensional irreducible representation of a complex semisimple Lie group. They are commutative finite flat algebras over the cohomology of the classifying space of the group. They are isomorphic with the equivariant intersection cohomology of affine Schubert varieties, endowing the latter with a new ring structure. Study of the finer aspects of the structure of the big algebras will also furnish the stalks of the intersection cohomology with ring structure, thus ringifying Lusztig's q-weight multiplicity polynomials i.e., certain affine Kazhdan-Lusztig polynomials.

5.
Proc Natl Acad Sci U S A ; 120(46): e2306736120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37931112

RESUMO

Photorespiration can limit gross primary productivity in terrestrial plants. The rate of photorespiration relative to carbon fixation increases with temperature and decreases with atmospheric [CO2]. However, the extent to which this rate varies in the environment is unclear. Here, we introduce a proxy for relative photorespiration rate based on the clumped isotopic composition of methoxyl groups (R-O-CH3) in wood. Most methoxyl C-H bonds are formed either during photorespiration or the Calvin cycle and thus their isotopic composition may be sensitive to the mixing ratio of these pathways. In water-replete growing conditions, we find that the abundance of the clumped isotopologue 13CH2D correlates with temperature (18-28 °C) and atmospheric [CO2] (280-1000 ppm), consistent with a common dependence on relative photorespiration rate. When applied to a global dataset of wood, we observe global trends of isotopic clumping with climate and water availability. Clumped isotopic compositions are similar across environments with temperatures below ~18 °C. Above ~18 °C, clumped isotopic compositions in water-limited and water-replete trees increasingly diverge. We propose that trees from hotter climates photorespire substantially more than trees from cooler climates. How increased photorespiration is managed depends on water availability: water-replete trees export more photorespiratory metabolites to lignin whereas water-limited trees either export fewer overall or direct more to other sinks that mitigate water stress. These disparate trends indicate contrasting responses of photorespiration rate (and thus gross primary productivity) to a future high-[CO2] world. This work enables reconstructing photorespiration rates in the geologic past using fossil wood.

6.
Proc Natl Acad Sci U S A ; 120(12): e2220320120, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36917669

RESUMO

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (ß-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Pré-Escolar , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , SARS-CoV-2 , Linfócitos T , Herpesvirus Humano 4 , Linfócitos T CD4-Positivos , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , Reações Cruzadas
7.
Circulation ; 150(9): 677-686, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39109427

RESUMO

BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is associated with higher survival for out-of-hospital cardiac arrest, but whether its association with survival differs by patients' sex and race and ethnicity is less clear. METHODS: Within a large US registry, we identified 623 342 nontraumatic out-of-hospital cardiac arrests during 2013 to 2022 for this observational cohort study. Using hierarchical logistic regression, we examined whether there was a differential association between bystander CPR and survival outcomes by patients' sex and race and ethnicity, overall and by neighborhood strata. RESULTS: Mean age was 62.1±17.1 years, and 35.9% were women. Nearly half of patients (49.8%) were non-Hispanic White; 20.6% were non-Hispanic Black; 7.3% were Hispanic; 2.9% were Asian; and 0.4% were Native American. Overall, 58 098 (9.3%) survived to hospital discharge. Although bystander CPR was associated with higher survival in each race and ethnicity group, the association of bystander CPR compared with patients without bystander CPR in each racial and ethnic group was highest in individuals who were White (adjusted odds ratio [OR], 1.33 [95% CI, 1.30-1.37]) and Native American (adjusted OR, 1.40 [95% CI, 1.02-1.90]) and lowest in individuals who were Black (adjusted OR, 1.09 [95% CI, 1.04-1.14]; Pinteraction<0.001). The adjusted OR for bystander CPR compared with those without bystander CPR for Hispanic patients was 1.29 (95% CI, 1.20-1.139), for Asian patients, it was 1.27 (95% CI, 1.12-1.42), and for those of unknown race, it was 1.31 (95% CI, 1.25-1.36). Similarly, bystander CPR was associated with higher survival in both sexes, but its association with survival was higher in men (adjusted OR, 1.35 [95% CI, 1.31-1.38]) than women (adjusted OR, 1.15 [95% CI, 1.12-1.19]; Pinteraction<0.001). The weaker association of bystander CPR in Black individuals and women was consistent across neighborhood race and ethnicity and income strata. Similar results were observed for the outcome of survival without severe neurological deficits. CONCLUSIONS: Although bystander CPR was associated with higher survival in all patients, its association with survival was weakest for Black individuals and women with out-of-hospital cardiac arrest.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/etnologia , Grupos Raciais , Sistema de Registros , Fatores Sexuais , Estados Unidos/epidemiologia
8.
Annu Rev Microbiol ; 74: 713-733, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32692612

RESUMO

Most methanogenic archaea use the rudimentary hydrogenotrophic pathway-from CO2 and H2 to methane-as the terminal step of microbial biomass degradation in anoxic habitats. The barely exergonic process that just conserves sufficient energy for a modest lifestyle involves chemically challenging reactions catalyzed by complex enzyme machineries with unique metal-containing cofactors. The basic strategy of the methanogenic energy metabolism is to covalently bind C1 species to the C1 carriers methanofuran, tetrahydromethanopterin, and coenzyme M at different oxidation states. The four reduction reactions from CO2 to methane involve one molybdopterin-based two-electron reduction, two coenzyme F420-based hydride transfers, and one coenzyme F430-based radical process. For energy conservation, one ion-gradient-forming methyl transfer reaction is sufficient, albeit supported by a sophisticated energy-coupling process termed flavin-based electron bifurcation for driving the endergonic CO2 reduction and fixation. Here, we review the knowledge about the structure-based catalytic mechanism of each enzyme of hydrogenotrophic methanogenesis.


Assuntos
Archaea/metabolismo , Metabolismo Energético , Hidrogênio/metabolismo , Metano/metabolismo , Complexos Multienzimáticos/química , Archaea/química , Archaea/enzimologia , Dióxido de Carbono/metabolismo , Dinitrocresóis/metabolismo , Transporte de Elétrons , Complexos Multienzimáticos/metabolismo , Oxirredução
9.
Am J Respir Crit Care Med ; 209(1): 83-90, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37523681

RESUMO

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.


Assuntos
Pulmão , Humanos , Estudos Transversais , Volume Expiratório Forçado , Valores de Referência , Espirometria/métodos , Capacidade Vital
10.
Artigo em Inglês | MEDLINE | ID: mdl-39116950

RESUMO

BACKGROUND: There are pre-existing inequities in asthma care. OBJECTIVES: We sought to evaluate effect modification by race of the effect of insurance on biologic therapy use in patients with asthma and related diseases. METHODS: We conducted inverse probability weighted analyses using electronic health records data from 2011 to 2020 from a large health care system in Boston, Mass. We evaluated the odds of not initiating omalizumab or mepolizumab therapy within 1 year of prescription for an approved indication. RESULTS: We identified 1132 individuals who met study criteria. Twenty-seven percent of these patients had public insurance and 12% belonged to a historically marginalized group (HMG). One-quarter of patients did not initiate the prescribed biologic. Among patients with asthma, individuals belonging to HMG had higher exacerbation rates in the period before initiation compared to non-HMG individuals, regardless of insurance type. Among HMG patients with asthma, those with private insurance were less likely to not initiate therapy compared to those with public insurance (odds ratio [OR]: 0.67, and 95% CI: 0.56-0.79). Among non-HMG with asthma, privately insured and publicly insured individuals had similar rates of not initiating the prescribed biologic (OR: 1.02; 95% CI: 0.95-1.09). Among those publicly insured with asthma, HMGs had higher odds of not initiating therapy compared to non-HMGs (OR: 1.16; 95% CI: 1.03-1.31), but privately insured HMG and non-HMG did not differ significantly (OR: 0.99; 95% CI: 0.91-1.07). CONCLUSIONS: Publicly insured individuals belonging to HMG are less likely to initiate biologics when prescribed despite having more severe asthma, while there are no inequities by insurance in individuals belonging to other groups.

11.
Nano Lett ; 24(34): 10547-10553, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39140754

RESUMO

Two-dimensional transition metal carbides/nitrides (MXenes) have shown great promise in various applications. However, mass production of MXenes suffers from the excessive use of toxic fluorine-containing reagents. Herein, a new method was validated for synthesizing MXenes from five MAX ceramics. The method features a minimized (stoichiometric) dosage of F-containing reagent (NaBF4) and polyols (glycerol, erythritol, and xylitol) as the reaction solvent. Due to the sweetness of polyols and the low environmental impact, we refer to this method as a "sweet" synthesis of MXenes. An in-depth molecular dynamics simulation study, combined with experimental kinetic parameters, further revealed that the diffusion of F- in the confined interplanar space is rate-determining for the etching reaction. The expansion of interlayer spacing by polyols effectively reduces the diffusion activation energy of F- and accelerates the etching reaction.

12.
Circulation ; 148(3): 220-228, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37191040

RESUMO

BACKGROUND: Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure. METHODS: We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States-based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request. RESULTS: Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7-6.3; P=0.0007) in White patients and +4.7 points (95% CI, 0.7-8.7; P=0.02) in Black patients, with no significant interaction by race and treatment (P=0.76). Other KCCQ scales showed similar results. CONCLUSIONS: Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Fatores Raciais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Glucose , Sódio , Volume Sistólico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Circulation ; 148(3): 241-252, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37459413

RESUMO

BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P<0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P<0.001 for both), and a higher risk of death (HR 1.92; P=0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.


Assuntos
Cardiomiopatias , Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Feminino , Estados Unidos/epidemiologia , Masculino , Brancos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Fatores de Risco , Arritmias Cardíacas , Taquicardia Ventricular/terapia , Taquicardia Ventricular/epidemiologia , Prevenção Primária
14.
Circulation ; 147(3): 190-200, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36334260

RESUMO

BACKGROUND: Social and psychosocial factors are associated with cardiovascular health (CVH). Our objective was to examine the contributions of individual-level social and psychosocial factors to racial and ethnic differences in population CVH in the NHANES (National Health and Nutrition Examination Surveys) 2011 to 2018, to inform strategies to mitigate CVH inequities. METHODS: In NHANES participants ages ≥20 years, Kitagawa-Blinder-Oaxaca decomposition estimated the statistical contribution of individual-level factors (education, income, food security, marital status, health insurance, place of birth, depression) to racial and ethnic differences in population mean CVH score (range, 0-14, accounting for diet, smoking, physical activity, body mass index, blood pressure, cholesterol, blood glucose) among Hispanic, non-Hispanic Asian, or non-Hispanic Black adults compared with non-Hispanic White adults. RESULTS: Among 16 172 participants (representing 255 million US adults), 24% were Hispanic, 12% non-Hispanic Asian, 23% non-Hispanic Black, and 41% non-Hispanic White. Among men, mean (SE) CVH score was 7.45 (2.3) in Hispanic, 8.71 (2.2) in non-Hispanic Asian, 7.48 (2.4) in non-Hispanic Black, and 7.58 (2.3) in non-Hispanic White adults. In Kitagawa-Blinder-Oaxaca decomposition, education explained the largest component of CVH differences among men (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.36 [0.04] points higher in Hispanic, 0.24 [0.04] points lower in non-Hispanic Asian, and 0.23 [0.03] points higher in non-Hispanic Black participants; P<0.05). Among women, mean (SE) CVH score was 8.03 (2.4) in Hispanic, 9.34 (2.1) in non-Hispanic Asian, 7.43 (2.3) in non-Hispanic Black, and 8.00 (2.5) in non-Hispanic White adults. Education explained the largest component of CVH difference in non-Hispanic Black women (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.17 [0.03] points higher in non-Hispanic Black participants; P<0.05). Place of birth (born in the United States versus born outside the United States) explained the largest component of CVH difference in Hispanic and non-Hispanic Asian women (if distribution of place of birth were similar to non-Hispanic White participants, CVH score would be 0.36 [0.07] points lower and 0.49 [0.16] points lower, respectively; P<0.05). CONCLUSIONS: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.


Assuntos
Etnicidade , Grupos Raciais , Masculino , Adulto , Humanos , Estados Unidos/epidemiologia , Feminino , Adulto Jovem , Inquéritos Nutricionais , Hispânico ou Latino , Dieta
15.
Circulation ; 148(3): 229-240, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37459415

RESUMO

BACKGROUND: Systems of care have been developed across the United States to standardize care processes and improve outcomes in patients with ST-segment-elevation myocardial infarction (STEMI). The effect of contemporary STEMI systems of care on racial and ethnic disparities in achievement of time-to-treatment goals and mortality in STEMI is uncertain. METHODS: We analyzed 178 062 patients with STEMI (52 293 women and 125 769 men) enrolled in the American Heart Association Get With The Guidelines-Coronary Artery Disease registry between January 1, 2015, and December 31, 2021. Patients were stratified into and outcomes compared among 3 racial and ethnic groups: non-Hispanic White, Hispanic White, and Black. The primary outcomes were the proportions of patients achieving the following STEMI process metrics: prehospital ECG obtained by emergency medical services; hospital arrival to ECG obtained within 10 minutes for patients not transported by emergency medical services; arrival-to-percutaneous coronary intervention time within 90 minutes; and first medical contact-to-device time within 90 minutes. A secondary outcome was in-hospital mortality. Analyses were performed separately in women and men, and all outcomes were adjusted for age, comorbidities, acuity of presentation, insurance status, and socioeconomic status measured by social vulnerability index based on patients' county of residence. RESULTS: Compared with non-Hispanic White patients with STEMI, Hispanic White patients and Black patients had lower odds of receiving a prehospital ECG and achieving targets for door-to-ECG, door-to-device, and first medical contact-to-device times. These racial disparities in treatment goals were observed in both women and men, and persisted in most cases after multivariable adjustment. Compared with non-Hispanic White women, Hispanic White women had higher adjusted in-hospital mortality (odds ratio, 1.39 [95% CI, 1.12-1.72]), whereas Black women did not (odds ratio, 0.88 [95% CI, 0.74-1.03]). Compared with non-Hispanic White men, adjusted in-hospital mortality was similar in Hispanic White men (odds ratio, 0.99 [95% CI, 0.82-1.18]) and Black men (odds ratio, 0.96 [95% CI, 0.85-1.09]). CONCLUSIONS: Race- or ethnicity-based disparities persist in STEMI process metrics in both women and men, and mortality differences are observed in Hispanic White compared with non-Hispanic White women. Further research is essential to evolve systems of care to mitigate racial differences in STEMI outcomes.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Doença da Artéria Coronariana/etiologia , American Heart Association , Intervenção Coronária Percutânea/efeitos adversos , Mortalidade Hospitalar , Sistema de Registros
16.
Circulation ; 147(19): 1471-1487, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37035919

RESUMO

Cardiovascular disease is the leading cause of death in women, yet differences exist among certain racial and ethnic groups. Aside from traditional risk factors, behavioral and environmental factors and social determinants of health affect cardiovascular health and risk in women. Language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented races and ethnicities. These factors result in a higher prevalence of cardiovascular disease and significant challenges in the diagnosis and treatment of cardiovascular conditions. Culturally sensitive, peer-led community and health care professional education is a necessary step in the prevention of cardiovascular disease. Equitable access to evidence-based cardiovascular preventive health care should be available for all women regardless of race and ethnicity; however, these guidelines are not equally incorporated into clinical practice. This scientific statement reviews the current evidence on racial and ethnic differences in cardiovascular risk factors and current cardiovascular preventive therapies for women in the United States.


Assuntos
Doenças Cardiovasculares , Etnicidade , Humanos , Feminino , Estados Unidos/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , American Heart Association , Fatores de Risco , Fatores de Risco de Doenças Cardíacas
17.
Stroke ; 55(8): 2034-2044, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39038094

RESUMO

BACKGROUND: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. METHODS: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. RESULTS: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). CONCLUSIONS: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.


Assuntos
Anti-Hipertensivos , Negro ou Afro-Americano , Hipertensão , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Transversais , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/epidemiologia , Brancos
18.
Clin Infect Dis ; 79(1): 141-147, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38306502

RESUMO

BACKGROUND: Equitable representation of members from historically marginalized groups is important in clinical trials, which inform standards of care. The goal of this study was to characterize the demographics and proportional subgroup reporting and representation of participants enrolled in randomized controlled trials (RCTs) of antibacterials used to treat Staphylococcus aureus infections. METHODS: We examined randomized controlled registrational and strategy trials published from 2000 to 2021 to determine the sex, race, and ethnicity of participants. Participant to incidence ratios (PIRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the disease population in each group. Underrepresentation was defined as a PIR < 0.8. RESULTS: Of the 87 included studies, 82 (94.2%) reported participant sex, 69 (79.3%) reported participant race, and 20 (23.0%) included ethnicity data. Only 17 (19.5%) studies enrolled American Indian/Alaskan Native participants. Median PIRs indicated that Asian and Black participants were underrepresented in RCTs compared with the incidence of methicillin-resistant S. aureus infections in these subgroups. Underrepresentation of Black participants was associated with a larger study size, international sites, industry sponsorship, and phase 2/3 trials compared with phase 4 trials (P < .05 for each). Black participants had more than 4 times the odds of being underrepresented in phase 2/3 trials compared with phase 4 trials (odds ratio, 4.57; 95% confidence interval: 1.14-18.3). CONCLUSIONS: Standardized reporting methods for race and ethnicity and efforts to increase recruitment of marginalized groups would help ensure equity, rigor, and generalizability in RCTs of antibacterial agents and reduce health inequities.


Assuntos
Antibacterianos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Estados Unidos/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Feminino , Masculino , Etnicidade , Grupos Raciais
19.
BMC Genomics ; 25(1): 179, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355396

RESUMO

BACKGROUND: Gene expression pattern is associated with biological phenotype and is widely used in exploring gene functions. Its evolution is also crucial in understanding species speciation and divergence. The genus Gossypium is a bona fide model for studying plant evolution and polyploidization. However, the evolution of gene expression during cotton species divergence has yet to be extensively discussed. RESULTS: Based on the seedling leaf transcriptomes, this work analyzed the transcriptomic content and expression patterns across eight cotton species, including six diploids and two natural tetraploids. Our findings indicate that, while the biological function of these cotton transcriptomes remains largely conserved, there has been significant variation in transcriptomic content during species divergence. Furthermore, we conducted a comprehensive analysis of expression distances across cotton species. This analysis lends further support to the use of G. arboreum as a substitute for the A-genome donor of natural cotton polyploids. Moreover, our research highlights the evolution of stress-responsive pathways, including hormone signaling, fatty acid degradation, and flavonoid biosynthesis. These processes appear to have evolved under lower selection pressures, presumably reflecting their critical role in the adaptations of the studied cotton species to diverse environments. CONCLUSIONS: In summary, this study provided insights into the gene expression variation within the genus Gossypium and identified essential genes/pathways whose expression evolution was closely associated with the evolution of cotton species. Furthermore, the method of characterizing genes and pathways under unexpected high or slow selection pressure can also serve as a new strategy for gene function exploration.


Assuntos
Gossypium , Transcriptoma , Gossypium/genética , Gossypium/metabolismo , Genes de Plantas , Perfilação da Expressão Gênica , Poliploidia , Regulação da Expressão Gênica de Plantas , Filogenia , Genoma de Planta
20.
BMC Genomics ; 25(1): 720, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054421

RESUMO

BACKGROUND: Paenibacillus polymyxa is a bacterial species of high interest, as suggested by the increased number of publications on its functions in the past years. Accordingly, the number of described strains and sequenced genomes is also on the rise. While functional diversity of P. polymyxa has been suggested before, the available genomic data is now sufficient for robust comparative genomics analyses. RESULTS: Using 157 genomes, we found significant disparities among strains currently affiliated to P. polymyxa. Multiple taxonomic groups were identified with conserved predicted functions putatively impacting their respective ecology. As strains of this species have been reported to exhibit considerable potential in agriculture, medicine, and bioremediation, it is preferable to clarify their taxonomic organization to facilitate reliable and durable approval as active ingredients. CONCLUSIONS: Strains currently affiliated to P. polymyxa can be separated into two major species groups with differential potential in nitrogen fixation, plant interaction, secondary metabolism, and antimicrobial resistance, as inferred from genomic data.


Assuntos
Variação Genética , Genoma Bacteriano , Genômica , Paenibacillus polymyxa , Filogenia , Paenibacillus polymyxa/genética , Genômica/métodos , Fixação de Nitrogênio/genética , Metabolismo Secundário/genética
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