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1.
Am J Clin Nutr ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788785

RESUMO

BACKGROUND: Vascular calcification contributes to cardiovascular disease (CVD) and mortality in individuals with chronic kidney disease (CKD). Vitamin K-dependent proteins function as calcification inhibitors in vascular tissue. OBJECTIVE: We sought to determine the association of vitamin K status with mortality and CVD events in adults with CKD. DESIGN: Plasma dephospho-uncarboxylated matrix gla protein ((dp)ucMGP), which increases when vitamin K status is low, and plasma phylloquinone (vitamin K1), which decreases when vitamin K status is low, were measured in 3066 Chronic Renal Insufficiency Cohort participants (median age = 61 years, 45% female, 41% non-Hispanic Black, median eGFR = 41 mL/min/1.73m2). The association of vitamin K status biomarkers with all-cause mortality and atherosclerotic-related CVD was determined using multivariable Cox proportional hazards regression. RESULTS: There were 1122 deaths and 599 atherosclerotic CVD events over the median 12.8 follow-up years. All-cause mortality risk was 21-29% lower among participants with plasma (dp)ucMGP <450 pmol/L (n = 2361) compared to those with plasma (dp)ucMGP ≥450 pmol/L [adjusted HRs (95%CIs): < 300 pmol/L = 0.71(0.61, 0.83), 300-449 pmol/L = 0.77(0.66, 0.90)] and 16-19% lower among participants with plasma phylloquinone ≥0.50 nmol/L (n = 2421) compared to those with plasma phylloquinone <0.50 nmol/L [adjusted HRs: 0.50, 0.99 nmol/L = 0.84(0.72, 0.99), ≥1.00 nmol/L = 0.81(0.70, 0.95)]. The risk for atherosclerotic CVD events did not significantly differ across plasma (dp)ucMGP or phylloquinone categories. CONCLUSIONS: Two biomarkers of vitamin K status were associated with a lower all-cause mortality risk but not atherosclerotic CVD events. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of improving vitamin K status in people with CKD.

2.
Biomed Environ Sci ; 34(10): 803-813, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34782046

RESUMO

Objective: The study aims to predict 10-year cardiovascular disease (CVD) risk and explore its association with sleep duration among Chinese urban adults. Methods: We analyzed part of the baseline data of a cohort that recruited adults for health screening by cluster sampling. The simplified Pittsburgh Sleep Quality Index (PSQI) and Framingham 10-year risk score (FRS) were used to measure sleep duration and CVD risk. Demographic characteristics, personal history of chronic diseases, lifestyle factors were collected using a questionnaire. Height, weight, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were also measured. Multiple logistic regression models were performed to explore the association of sleep duration with the predicted CVD risk. Results: We included 31, 135 participants (median age 44 years, 53.02% males) free of CVD, cerebral stroke, and not taking lipid-lowering agents. Overall, 14.05%, and 25.55% of participants were at medium and high predicted CVD risk, respectively. Short sleep was independently associated with increased odds of medium to high risk of predicted 10-year CVD among males ( OR = 1.10; 95% CI: 1.01-1.19) and increased odds of medium to high and high risk of predicted 10-year CVD among females ( OR = 1.23; 95% CI: 1.08-1.40; OR = 1.27; 95% CI: 1.11-1.44). In contrast, long sleep had no association with cardiovascular risk. Conclusion: A substantial number of adults free of CVD were at high 10-year CVD risk. Short sleep was associated with increased odds of predicted CVD risk.

3.
MedComm (Beijing) ; 2(3): 467-480, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34766156

RESUMO

Gastric cancer (GC) is one of the most familiar malignancy in the digestive system. Demethylzeylasteral (Dem), a natural functional monomer extracted from Tripterygium wilfordii Hook F, shows anti-tumor effects in a variety of cancers, including GC, however, with the underlying mechanism poorly understood. In our study, we show that Dem inhibits the proliferation, migration, and invasion of GC cells, which are mediated by down-regulating c-Myc protein levels. Mechanistically, Dem reduces the stability of c-Myc by up-regulating FBXW7, an E3 ubiquitin ligase. Moreover, in xenograft tumor model experiment, Dem also inhibits GC, which depends on suppressing c-Myc expression. Finally, Dem enhances GC cell chemosensitivity to the combination treatment of 5-Fluorouracil (5-Fu) and doxorubicin (DOX) in vitro. Together, Dem exerts anti-neoplastic activities through destabilizing and suppressing c-Myc, establishing a theory foundation for using it in future treatment of GC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34674134

RESUMO

The behavior and risk of arsenic (As) closely relate to its geochemical fractionation and environmental factors in sediments. The soluble (F1), reducible (F2), oxidizable (F3), and residual fraction (F4) of As were extracted in the sediments from Lake Hulun, Wuliangsuhai, and Dalinor of Inner Mongolia Plateau. Coupled with lakes from Eastern and Northeast Plain, Yunnan-Guizhou and Qinghai-Tibetan Plateau, the responses of As fractions to environmental conditions were investigated according to the spatial distribution of As fractionations in five lake ecoregions at a national scale of China. Generally, F1 was more sensitive to environmental changes, and the pH presented significantly negative effects on the amount of soluble As, while water depth played an important role in regulating the distribution of the fraction F2 and F4. The As pools in surface lake sediments presented a latitudinal zonation due to the gradient effects of climate and anthropogenic activities on nutrient decomposition, and their influence on the capacity of sediments holding As. This work indicated that nutrients played a coordinating role in regulating the impacts of climate and environmental factors on As fractionation in aquatic environments.

5.
Yi Chuan ; 43(9): 822-834, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702696

RESUMO

Transposable elements (TEs) are the most prevalent elements in mammalian genomes. Although potential risks for genome stability, they are a pool of potential regulatory sequences, chromatin control elements, protein-coding genes, and substrates for evolutionary processes. Consequently, a delicate balance is maintained between the potential benefits and deleterious aspects of TEs, and this balance is mediated by the epigenetic regulatory system. In this review, we introduce the role of heterochromatin associated epigentic modifications such as histone 3 lysine 9 trimethylation (H3K9me3) and DNA methylation in the silencing of TEs as well as epigenetic modifications such as histone 3 lysine 4 monomethylation (H3K4me1) and histone 3 lysine 27 acetylation (H3K27ac) in activation of TEs. Further, we elaborate the functions of TEs as binding sites of transcription factors and as anchors of chromosomal conformation in regulation of gene expression. We introduce the impact of TEs on the process of cell fate determination including natural embryonic development in vivo and artificial cell fate transition in vitro. We discuss the main challenges associated with computational TEs analysis and TEs functions exploration, as well as the different experimental and computational strategies in studying these processes. In all, this article provides a comprehensive review of the research advances and existing problems in study of transposable elements in epigenetic regulatory mechanisms, gene transcriptional regulation, and cell fate determination, thereby providing some references for researchers in the fields.


Assuntos
Elementos de DNA Transponíveis , Epigênese Genética , Animais , Metilação de DNA , Elementos de DNA Transponíveis/genética , Epigenômica , Histonas/metabolismo
7.
JAMA ; 326(13): 1286-1298, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609450

RESUMO

Importance: After decades of decline, the US cardiovascular disease mortality rate flattened after 2010, and racial and ethnic differences in cardiovascular disease mortality persisted. Objective: To examine 20-year trends in cardiovascular risk factors in the US population by race and ethnicity and by socioeconomic status. Design, Setting, and Participants: A total of 50 571 participants aged 20 years or older from the 1999-2018 National Health and Nutrition Examination Surveys, a series of cross-sectional surveys in nationally representative samples of the US population, were included. Exposures: Calendar year, race and ethnicity, education, and family income. Main Outcomes and Measures: Age- and sex-adjusted means or proportions of cardiovascular risk factors and estimated 10-year risk of atherosclerotic cardiovascular disease were calculated for each of 10 two-year cycles. Results: The mean age of participants ranged from 49.0 to 51.8 years and the proportion of women from 48.2% to 51.3% in the surveys. From 1999-2000 to 2017-2018, age- and sex-adjusted mean body mass index increased from 28.0 (95% CI, 27.5-28.5) to 29.8 (95% CI, 29.2-30.4); mean hemoglobin A1c increased from 5.4% (95% CI, 5.3%-5.5%) to 5.7% (95% CI, 5.6%-5.7%) (both P < .001 for linear trends). Mean serum total cholesterol decreased from 203.3 mg/dL (95% CI, 200.9-205.8 mg/dL) to 188.5 mg/dL (95% CI, 185.2-191.9 mg/dL); prevalence of smoking decreased from 24.8% (95% CI, 21.8%-27.7%) to 18.1% (95% CI, 15.4%-20.8%) (both P < .001 for linear trends). Mean systolic blood pressure decreased from 123.5 mm Hg (95% CI, 122.2-124.8 mm Hg) in 1999-2000 to 120.5 mm Hg (95% CI, 119.6-121.3 mm Hg) in 2009-2010, then increased to 122.8 mm Hg (95% CI, 121.7-123.8 mm Hg) in 2017-2018 (P < .001 for nonlinear trend). Age- and sex-adjusted 10-year atherosclerotic cardiovascular disease risk decreased from 7.6% (95% CI, 6.9%-8.2%) in 1999-2000 to 6.5% (95% CI, 6.1%-6.8%) in 2011-2012, then did not significantly change. Age- and sex-adjusted body mass index, systolic blood pressure, and hemoglobin A1c were consistently higher, while total cholesterol was lower in non-Hispanic Black participants compared with non-Hispanic White participants (all P < .001 for group differences). Individuals with college or higher education or high family income had consistently lower levels of cardiovascular risk factors. The mean age- and sex-adjusted 10-year risk of atherosclerotic cardiovascular disease was significantly higher in non-Hispanic Black participants compared with non-Hispanic White participants (difference, 1.4% [95% CI, 1.0%-1.7%] in 1999-2008 and 2.0% [95% CI, 1.7%-2.4%] in 2009-2018]). This difference was attenuated (-0.3% [95% CI, -0.6% to 0.1%] in 1999-2008 and 0.7% [95% CI, 0.3%-1.0%] in 2009-2018) after further adjusting for education, income, home ownership, employment, health insurance, and access to health care. Conclusions and Relevance: In this serial cross-sectional survey study that estimated US trends in cardiovascular risk factors from 1999 through 2018, differences in cardiovascular risk factors persisted between Black and White participants; the difference may have been moderated by social determinants of health.


Assuntos
Doenças Cardiovasculares/etnologia , Grupos de Populações Continentais/etnologia , Grupos Étnicos , Fatores de Risco de Doenças Cardíacas , Classe Social , Adulto , Fatores Etários , Idoso , Aterosclerose/epidemiologia , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Colesterol/sangue , Intervalos de Confiança , Estudos Transversais , Escolaridade , Feminino , Hemoglobina A Glicada/análise , Humanos , Renda/tendências , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/tendências , Prevalência , Fatores Sexuais , Fumar/epidemiologia , Fumar/tendências , Determinantes Sociais da Saúde/etnologia , Determinantes Sociais da Saúde/tendências , Fatores de Tempo , Estados Unidos/etnologia , Adulto Jovem
8.
Am J Cardiol ; 159: 121-128, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34656312

RESUMO

Deceleration in the decline of cardiovascular disease mortality has been observed recently in the US. We aimed to examine the recent secular trends of cardiovascular health metrics in the US general population. A total of 32,832 adults aged ≥20 years from the National Health and Nutrition Examination Surveys 2007 to 2018 were included in this analysis. Cardiovascular health included 7 health metrics: smoking status, body mass index, physical activity, healthy diet score, total cholesterol, blood pressure, and fasting plasma glucose. Age-standardized mean of overall cardiovascular health score did not significantly change during 2007 to 2010, 2011 to 2014, and 2015 to 2018 in the US adult population (7.88, 8.03, and 7.91, respectively, P-trend = 0.85). The age-standardized proportions of ideal smoking status (P-trend = 0.003), ideal physical activity (P-trend = 0.03), and untreated total cholesterol <200 mg/dL (P-trend <0.001) were significantly increased but the proportions of body mass index <25.0 kg/m2 (P-trend <0.001), systolic/diastolic blood pressure <120/80 mmHg (P-trend = 0.02), and fasting plasma glucose <100 mg/dL (P-trend <0.001) were significantly decreased during the same period of time in the US adults. In conclusion, from 2007 to 2018, overall cardiovascular health did not change in the US general adult population. Of note, body mass index, blood pressure, and fasting plasma glucose significantly worsened during the same period.

9.
Am J Prev Cardiol ; 7: 100190, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34611635

RESUMO

Objective: A significant proportion of persons with metabolic syndrome (MetS), prediabetes, or type 2 diabetes (T2D) do not develop atherosclerotic cardiovascular disease (ASCVD).We sought to determine whether discordantly normal apolipoprotein B (ApoB) relative to elevated LDL-C may help to explain heterogeneity in ASCVD risk among persons with metabolic disorders. Methods: There were 278 Bogalusa Heart Study participants with MetS (n=95), prediabetes (n=233), or T2D (n=31) and LDL-C ≥100 mg/dL who were free of carotid plaque at baseline (2001-02) and underwent carotid ultrasound at follow-up (2013-16). Multivariable modified Poisson regression estimated the long-term absence of carotid plaque for lower ApoB, continuously and categorically. Results: Participants were on average 36.1 years old at baseline, 61.5% were women, and 31.7% were black. A total of 50.7% had discordantly normal ApoB (<90 mg/dL) and the mean ApoB and LDL-C concentrations were 91.6 mg/dL and 137.7 mg/dL, respectively. In addition to having higher HDL-C and lower triglyceride values, individuals with ApoB <90 were more likely to maintain persistent absence of plaque compared to those with ApoB ≥90 (73.1% versus 58.4%, p=0.01). Contrastingly, there was no significant difference in the proportion of individuals who remained free of plaque with increasing LDL-C (p=0.45). Independent of traditional risk factors including LDL-C, each 10 mg/dL lower ApoB (RR=1.11, 95% CI: 1.03-1.19) and ApoB <90 (RR=1.22, 95% CI: 1.00-1.43) were significantly associated with the persistent absence of carotid plaque. Conclusions: One-half of young persons with metabolic disorders and elevated LDL-C had discordantly normal ApoB and a low burden of carotid atherosclerosis over 13 years, suggesting that ApoB better represents the atherogenic lipid burden compared to LDL-C in this patient population. These results suggest a utility for assessing whether routine ApoB measurement can improve ASCVD risk stratification in young persons with metabolic disorders who have high triglycerides and low HDL-cholesterol.

10.
Clin J Am Soc Nephrol ; 16(7): 1015-1024, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34597264

RESUMO

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated C-index; calibration was evaluated graphically and with the Grønnesby and Borgan test. RESULTS: Mean (SD) age of participants was 57 (11) years, 55% were men, 38% were Black, and mean (SD) eGFR was 45 (15) ml/min per 1.73 m2; 259 incident AF events occurred during a median of 8 years of follow-up. The CHARGE-AF prediction equation using original and re-estimated coefficients had C-indices of 0.67 (95% confidence interval, 0.64 to 0.71) and 0.67 (95% confidence interval, 0.64 to 0.70), respectively. A likelihood-based boosting model using clinical variables only had a C-index of 0.67 (95% confidence interval, 0.64 to 0.70); adding N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or both biomarkers improved the C-index by 0.04, 0.01, and 0.04, respectively. In addition to N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, the final model included age, non-Hispanic Black race/ethnicity, Hispanic race/ethnicity, cardiovascular disease, chronic obstructive pulmonary disease, myocardial infarction, peripheral vascular disease, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, calcium channel blockers, diuretics, height, and weight. CONCLUSIONS: Using machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.

11.
JAMA Netw Open ; 4(9): e2122559, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519769

RESUMO

Importance: Hypertension is highly prevalent in low- and middle-income countries, and it is an important preventable risk factor for cardiovascular diseases (CVDs). Understanding the economic benefits of a hypertension control program is valuable to decision-makers. Objective: To evaluate the long-term cost-effectiveness of a multicomponent hypertension management program compared with usual care among patients with hypertension receiving care in public clinics in Argentina from a health care system perspective. Design, Setting, and Participants: This economic evaluation used a Markov model to estimate the cost-effectiveness of a hypertension management program among adult patients with uncontrolled hypertension in a low-income setting. Patient-level data (743 individuals for multicomponent intervention; 689 for usual care) from the Hypertension Control Program in Argentina trial (HCPIA) were used to estimate treatment effects and the risk of CVD. Three health states were included in each strategy: (1) low risk of CVD, (2) high risk of CVD, and (3) death. The total time horizon was the lifetime, and each cycle lasted 6 months. Main Outcomes and Measures: Model inputs were based on trial data and other published sources. Cost and utilities were discounted at a rate of 5% annually. The incremental cost-effectiveness ratio (ICER) between the multicomponent intervention and usual care was calculated using the difference in costs in 2017 international dollars (INT $) divided by the difference in effectiveness in quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty and robustness of the results. Results: In the original trial, the 743 participants in the intervention group (349 [47.0%] men) had a mean (SD) age of 56.2 (12.0) years, and the 689 participants in the control group (311 [45.1%] men) had a mean (SD) age of 56.2 (11.7) years. In the base-case analysis, the HCPIA program yielded 8.42 discounted QALYs and accrued INT $3096 discounted costs, while usual care yielded 8.29 discounted QALYs and accrued INT $2473 discounted costs. The ICER for the HCPIA program was INT $4907/QALY gained. The model results remained robust in sensitivity analyses, and the model was most sensitive to parameters of program costs. Conclusions and Relevance: In this study, the HCPIA multicomponent intervention vs usual care was a cost-effective strategy to improve hypertension management and reduce the risk of associated CVD among patients with hypertension who received services at public clinics in Argentina. This intervention program is likely transferable to other settings in Argentina or other lower- and middle-income countries.

12.
BMC Health Serv Res ; 21(1): 908, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479559

RESUMO

BACKGROUND: Uncontrolled hypertension represents a substantial and growing burden in Guatemala and other low and middle-income countries. As a part of the formative phase of an implementation research study, we conducted a needs assessment to define short- and long-term needs and opportunities for hypertension services within the public health system. METHODS: We conducted a multi-method, multi-level assessment of needs related to hypertension within Guatemala's public system using the World Health Organization's health system building blocks framework. We conducted semi-structured interviews with stakeholders at national (n = 17), departmental (n = 7), district (n = 25), and community (n = 30) levels and focus groups with patients (3) and frontline auxiliary nurses (3). We visited and captured data about infrastructure, accessibility, human resources, reporting, medications and supplies at 124 health posts and 53 health centers in five departments of Guatemala. We conducted a thematic analysis of transcribed interviews and focus group discussions supported by matrix analysis. We summarized quantitative data observed during visits to health posts and centers. RESULTS: Major challenges for hypertension service delivery included: gaps in infrastructure, insufficient staffing and high turnover, limited training, inconsistent supply of medications, lack of reporting, low prioritization of hypertension, and a low level of funding in the public health system overall. Key opportunities included: prior experience caring for patients with chronic conditions, eagerness from providers to learn, and interest from patients to be involved in managing their health. The 5 departments differ in population served per health facility, accessibility, and staffing. All but 7 health posts had basic infrastructure in place. Enalapril was available in 74% of health posts whereas hydrochlorothiazide was available in only 1 of the 124 health posts. With the exception of one department, over 90% of health posts had a blood pressure monitor. CONCLUSIONS: This multi-level multi-method needs assessment using the building blocks framework highlights contextual factors in Guatemala's public health system that have been important in informing the implementation of a hypertension control trial. Long-term needs that are not addressed within the scope of this study will be important to address to enable sustained implementation and scale-up of the hypertension control approach.


Assuntos
Hipertensão , Programas Governamentais , Guatemala/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Determinação de Necessidades de Cuidados de Saúde , Atenção Primária à Saúde
13.
Artigo em Inglês | MEDLINE | ID: mdl-34493532

RESUMO

BACKGROUND AND PURPOSE: The association between annual household income and prognosis of ischaemic stroke remains debatable. We aimed to prospectively investigate the relationship between annual household income and prognosis at 3 months after ischaemic stroke. METHODS: We included 3975 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. All participants were categorised into three groups according to annual household income per capita: <¥10 000 (Chinese Yuan Renminbi (RMB)), ¥10 000-19 999 and ≥¥20 000. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset, and secondary outcomes included major disability, death, and vascular events. A meta-analysis was conducted to incorporate the results of the current study and previous studies on the association of income level with outcomes after stroke. RESULTS: Within 3 months after ischaemic stroke, 1002 participants (25.20%) experienced primary outcome (880 major disabilities and 122 deaths). After multivariate adjustment, low annual household income level was associated with increased risk of the primary outcome (OR 1.60; 95% CI: 1.12 to 2.31; Ptrend=0.034) when two extreme groups were compared. The meta-analysis confirmed the significant association between income level and death or major disability after stroke (pooled relative risk for lowest vs highest income level, 1.31 (95% CI: 1.18 to 1.45)). CONCLUSIONS: Low annual household income per capita was significantly associated with increased risks of adverse clinical outcomes at 3 months after ischaemic stroke, independently of established risk factors. Further studies from other samples are needed to replicate our findings due to a reason for excluding some patients who had a severe stroke in this study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (http://wwwclinicaltrialsgov) Registry (NCT01840072).

14.
Am J Cardiol ; 160: 117-123, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583809

RESUMO

The accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in discriminating lower extremity peripheral artery disease (PAD) has not been evaluated in patients with chronic kidney disease (CKD). We measured ABI, TBI, and Doppler ultrasound in 100 predialysis patients with CKD without revascularization or amputation. Leg-specific ABI was calculated using higher systolic blood pressure (SBP) in posterior tibial or dorsalis pedis artery divided by higher brachial SBP; alternative ABI was calculated using lower SBP in posterior tibial or dorsalis pedis artery. PAD was defined as ≥50% stenosis detected by Doppler ultrasound. PAD risk classification score was calculated using cardiovascular disease risk factors. The area under the curve (AUC, 95% confidence interval [CI]) for discriminating ultrasound-diagnosed PAD was 0.78 (0.69 to 0.87) by ABI, 0.80 (0.71 to 0.89) by alternative ABI, and 0.74 (0.63 to 0.86) by TBI. Sensitivity and specificity were 25% and 97% for ABI ≤0.9, 41% and 95% for alternative ABI ≤0.9, and 45% and 93% for TBI ≤0.7, respectively. AUC (95% CI) of PAD risk classification score was 0.86 (0.78 to 0.94) with sensitivity and specificity of 95% and 60% for risk score ≥0.10, 76% and 76% for risk score ≥0.25, and 43% and 95% for risk score ≥0.55. Combining risk score with ABI, alternative ABI, and TBI increased AUC (95% CI) to 0.89 (0.82 to 0.96), 0.89 (0.80 to 0.98), and 0.87 (0.78 to 0.96), respectively. In conclusion, current ABI and TBI diagnostic criteria have high specificity but low sensitivity for classifying PAD in patients with CKD. PAD classification risk score based on cardiovascular disease risk factors improves the accuracy of PAD classification.


Assuntos
Índice Tornozelo-Braço , Doença Arterial Periférica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Ultrassonografia Doppler , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Artéria Braquial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Insuficiência Renal Crônica/complicações , Medição de Risco , Sensibilidade e Especificidade , Artérias da Tíbia/fisiopatologia , Dedos do Pé/irrigação sanguínea
15.
N Engl J Med ; 385(19): 1750-1760, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34554660

RESUMO

BACKGROUND: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed. METHODS: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels. RESULTS: Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P10], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m2; 95% CI, -0.29 to 2.54; P10, 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m2; 95% CI, -0.12 to 2.33; P10, 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m2; 95% CI, -1.43 to 1.92) and accurate (P10, 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C. CONCLUSIONS: The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).


Assuntos
Grupos de Populações Continentais , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/etnologia , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Algoritmos , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Estados Unidos
16.
Angew Chem Int Ed Engl ; 60(44): 23713-23721, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34409728

RESUMO

Biofuel production can alleviate reliance on fossil resources and thus carbon dioxide emission. Hydrodeoxygenation (HDO) refers collectively to a series of important biorefinery processes to produce biofuels. Here, well-dispersed and ultra-small Ru metal nanoclusters (ca. 1 nm), confined within the micropores of zeolite Y, provide the required active site intimacy, which significantly boosts the chemoselectivity towards the production of pentanoic biofuels in the direct, one-pot HDO of neat ethyl levulinate. Crucial for improving catalyst stability is the addition of La, which upholds the confined proximity by preventing zeolite lattice deconstruction during catalysis. We have established and extended an understanding of the "intimacy criterion" in catalytic biomass valorization. These findings bring new understanding of HDO reactions over confined proximity sites, leading to potential application for pentanoic biofuels in biomass conversion.

17.
Atherosclerosis ; 332: 33-40, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34375911

RESUMO

BACKGROUND AND AIMS: Osteopontin is implicated in atherosclerosis, and its expression is upregulated in response to brain injury. The aim of this study was to prospectively investigate the associations between plasma osteopontin levels and adverse clinical outcomes in ischemic stroke patients. METHODS: We measured baseline plasma osteopontin levels in 3545 ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was the composite outcome of death and major disability (modified Rankin scale score ≥3) at 1 year after ischemic stroke, and secondary outcomes included major disability, death, and the composite outcome of death and vascular events. RESULTS: During 1 year of follow-up, patients in the fourth quartile of plasma osteopontin had the highest risks of primary outcome, major disability, death, and the composite outcome of death and vascular events. After multivariate adjustment, the odds ratios or hazard ratios (95 % confidence intervals) associated with each standard deviation increase in log-transformed osteopontin were 1.20 (1.09-1.33) for primary outcome, 1.11 (1.00-1.23) for major disability, 1.29 (1.10-1.52) for death, and 1.15 (1.01-1.30) for the composite outcome of death and vascular events. The addition of plasma osteopontin to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement: 16.91%, p < 0.001; integrated discrimination improvement: 0.43%, p = 0.002). CONCLUSIONS: Elevated plasma osteopontin levels at baseline were associated with increased risks of adverse clinical outcomes at 1 year after ischemic stroke, suggesting that osteopontin is a promising prognostic biomarker for ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Isquemia Encefálica/diagnóstico , Humanos , Osteopontina , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico
19.
Science ; 373(6558): 1030-1035, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34385354

RESUMO

Biological mechanisms underlying human germline mutations remain largely unknown. We statistically decompose variation in the rate and spectra of mutations along the genome using volume-regularized nonnegative matrix factorization. The analysis of a sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. We provide a biological interpretation for seven of these processes. We associate one process with bulky DNA lesions that are resolved asymmetrically with respect to transcription and replication. Two processes track direction of replication fork and replication timing, respectively. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions and a mutagenic effect of long interspersed nuclear elements. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric.


Assuntos
Genoma Humano , Mutação em Linhagem Germinativa , Algoritmos , Ilhas de CpG , Dano ao DNA , Desmetilação do DNA , Análise Mutacional de DNA , Replicação do DNA , Variação Genética , Células Germinativas , Humanos , Elementos Nucleotídeos Longos e Dispersos , Mutagênese , Oócitos/fisiologia , Transcrição Genética
20.
ACS Synth Biol ; 10(9): 2231-2242, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34464083

RESUMO

The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both in vivo using exogenously administered nanoparticle sensors and ex vivo using quenched fluorescent probes. We envision that this work will lay the foundation for how synthetic biology and nanotechnology can be meaningfully integrated to achieve next-generation engineered biosensors.

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