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1.
J Biomed Semantics ; 10(1): 10, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151407

RESUMO

BACKGROUND: We introduce TranScriptML, a semantic representation schema for prescription regimens allowing various properties of prescriptions (e.g. dose, frequency, route) to be specified separately and applied (manually or automatically) as annotations to patient instructions. In this paper, we describe the annotation schema, the curation of a corpus of prescription instructions through a manual annotation effort, and initial experiments in modeling and automated generation of TranScriptML representations. RESULTS: TranScriptML was developed in the process of curating a corpus of 2914 ambulatory prescriptions written within the Partners Healthcare network, and its schema is informed by the content of that corpus. We developed the representation schema as a novel set of semantic tags for prescription concept categories (e.g. frequency); each tag label is defined with an accompanying attribute framework in which the meaning of tagged concepts can be specified in a normalized fashion. We annotated a subset (1746) of this dataset using cross-validation and reconciliation between multiple annotators, and used Conditional Random Field machine learning and various other methods to train automated annotation models based on the manual annotations. The TranScriptML schema implementation, manual annotation, and machine learning were all performed using the MITRE Annotation Toolkit (MAT). We report that our annotation schema can be applied with varying levels of pairwise agreement, ranging from low agreement levels (0.125 F for the relatively rare REFILL tag) to high agreement levels approaching 0.9 F for some of the more frequent tags. We report similarly variable scores for modeling tag labels and spans, averaging 0.748 F-measure with balanced precision and recall. The best of our various attribute modeling methods captured most attributes with accuracy above 0.9. CONCLUSIONS: We have described an annotation schema for prescription regimens, and shown that it is possible to annotate prescription regimens at high accuracy for many tag types. We have further shown that many of these tags and attributes can be modeled at high accuracy with various techniques. By structuring the textual representation through annotation enriched with normalized values, the text can be compared against the pharmacist-entered structured data, offering an opportunity to detect and correct discrepancies.

2.
Sci Total Environ ; 670: 398-410, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30904653

RESUMO

The occurrence of UV-filters in the environment has raised concerns over potentially adverse impacts on corals. In this study, the concentrations of 13 UV-filters and 11 hormones were measured in surface seawater, sediment, and coral tissue from 19 sites in Oahu, Hawaii. At least eight UV-filters were detected in seawater, sediment, and coral tissue and total mass concentrations of all UV-filters were <750 ng L-1, <70 ng g-1 dry weight (dw), and <995 ng g-1 dw, respectively. Four UV-filters were detected in water, sediment, and coral tissue at detection frequencies of 63-100%, 56-91%, and 82-100%, respectively. These UV-filter concentrations generally varied as follows: water, homosalate (HMS) > octisalate (OS) > benzophenone-3 (BP-3, also known as oxybenzone) > octocrylene (OC); sediment, HMS > OS > OC > BP-3; coral, OS ≈ HMS > OC ≈ BP-3. BP-3 concentrations in surface seawater were <10 ng L-1 at 12 of 19 sites and highest at Waikiki beach (e.g., 10.9-136 ng L-1). While BP-3 levels were minimal in sediment (e.g., <1 ng g-1 dw at 18 of 19 sites), and ranged from 6.6 to 241 ng g-1 dw in coral tissue. No quantifiable levels of 2-ethylhexyl 4-methoxycinnamate (also known as octinoxate) were recorded in surface seawater or coral tissues, but 5-12.7 ng g-1 dw was measured for sediment at 5 of 19 sites. No hormones were detected in seawater or sediment, but 17α-ethinylestradiol was present in three corals from Kaneohe Bay. Surfactant degradation products were present in seawater, especially at Waikiki beach. These results demonstrate ubiquitous parts-per-trillion concentrations of UV-filters in surface seawater and is the first report of UV-filters in coral tissue from U.S.A. coastal waters. These data inform the range of environmentally-relevant concentrations for future risk assessments on the potential impacts of UV-filters on coral reefs in Oahu, Hawaii.


Assuntos
Monitoramento Ambiental , Água do Mar/química , Protetores Solares/análise , Poluentes Químicos da Água/análise , Acrilatos , Animais , Antozoários , Benzofenonas , Recifes de Corais , Hawaii , Salicilatos
3.
Am J Prev Med ; 56(2): 224-231, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30661571

RESUMO

INTRODUCTION: Financial hardship is associated with coronary heart disease risk factors, and may disproportionately affect some African American groups. This study examines whether stress because of financial hardship is associated with incident coronary heart disease in African Americans. METHODS: The Jackson Heart Study is a longitudinal cohort study of cardiovascular disease risks in African Americans in the Jackson, Mississippi metropolitan statistical area. Participant enrollment began in 2000. Analyses were performed in 2017 and included adjudicated endpoints through December 2012. Financial stress was assessed from the Jackson Heart Study Weekly Stress Inventory and categorized into four levels: (1) did not experience financial stress, (2) no stress, (3) mild stress, and (4) moderate to high stress. Incident coronary heart disease was defined as the first event of definite or probable myocardial infarction, definite fatal myocardial infarction, definite fatal coronary heart disease, or cardiac procedure. There were 2,256 individuals in this analysis. RESULTS: Participants with moderate to high (versus no) financial stress were more likely to have incident coronary heart disease events after controlling for demographics, SES, access to care, and traditional clinical risk factors (hazard ratio=2.42, 95% CI=1.13, 5.17). The association between financial stress and coronary heart disease was no longer statistically significant in a model adjusting for three specific risk factors: depression, smoking status, and diabetes (hazard ratio=1.99, 95% CI=0.91, 4.39). CONCLUSIONS: Financial stress may be an unrecognized risk factor for coronary heart disease for African Americans. Additional research should examine these associations in intervention studies that address perceived stress, in addition to other coronary heart disease risk factors, in patients experiencing financial stress.

4.
Clin Breast Cancer ; 19(3): 178-187.e3, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30685264

RESUMO

BACKGROUND: The effect of racial residential segregation on breast cancer treatment disparities is unclear. We examined whether racial segregation is associated with adjuvant treatment receipt and patient knowledge of disease. PATIENTS AND METHODS: We surveyed a population-based sample of women in Northern California with stage I to III breast cancer diagnosed in 2010 to 2011 (participation rate = 68.5%, 500 patients). For black, Hispanic, and white women, we measured black and Hispanic segregation using the location quotient (LQ) of racial residential segregation, a proportional measure of the size of a minority group in the census tract compared with the larger metropolitan statistical area. We categorized LQ values for black and Hispanic participants into quartiles, with quartile 1 representing a lower relative level of segregation than quartile 4. We used multivariable logistical regression to assess the odds of receiving guideline-recommended adjuvant therapy and patient knowledge of tumor characteristics according to relative residential segregation. RESULTS: We observed greater residential segregation for black versus Hispanic patients (P < .05). Overall, there were no treatment differences according to Hispanic or black LQ, except for black LQ quartile 3 (vs. 1) for which we observed higher odds of hormonal therapy. Knowledge of disease did not vary according to black LQ, but patients in the Hispanic LQ quartile 3 (vs. quartile 1) had less tumor knowledge. CONCLUSION: We did not find clear associations for racial residential segregation and treatment or cancer knowledge in Northern California, an area with low levels of segregation. Additional research should assess the effect of segregation on breast cancer treatment disparities in a variety of geographical locations.

5.
J Gen Intern Med ; 33(10): 1729-1737, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30076569

RESUMO

BACKGROUND: Use of breast cancer screening is influenced by factors associated with patients, primary care providers, practices, and health systems. OBJECTIVE: We examined the relative effects of these nested levels on four breast cancer screening metrics. DESIGN: A web-based survey was completed at 15 primary care practices within two health systems representing 306 primary care providers (PCPs) serving 46,944 women with a primary care visit between 1/2011-9/2014. Analyses occurred between 1/2017 and 5/2017. MAIN MEASURES: Across four nested levels (patient, PCP, primary care practice, and health system), frequency distributions and adjusted rates of primary care practice characteristics and survey results for four breast screening metrics (percent screened overall, and percent screened age 40-49, 50-74, and 75+) were reported. We used hierarchical multi-level mixed and random effects analysis to assess the relative influences of PCP, primary care practice, and health system on the breast screening metrics. KEY RESULTS: Overall, the proportion of women undergoing breast cancer screening was 73.1% (73.4% for ages 40-49, 76.5% for 50-74, and 51.1% for 75+). Patient ethnicity and number of primary care visits were strongly associated with screening rates. After adjusting for woman-level factors, 24% of the overall variation among PCPs was attributable to the primary care practice level, 35% to the health system level, and 41% to the residual variation among PCPs within practice. No specific provider-level characteristics were found to be statistically significant determinants of screening rates. CONCLUSIONS: After accounting for woman-level characteristics, the remaining variation in breast cancer screening was largely due to provider and health system variation.

6.
Prev Chronic Dis ; 15: E10, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29346062

RESUMO

BACKGROUND: Prolonged television viewing time, a marker of sedentary activity, is independently associated with increased all-cause mortality; however, this association has rarely been studied in African Americans. The objective of our study was to examine the association between television viewing time and mortality among African Americans by using data from the Jackson Heart Study (JHS). METHODS: We studied 5,289 participants from the JHS study who reported television viewing time (h/day) in the JHS baseline questionnaire from 2000 through 2004. Using multivariable Cox regression models adjusted for age, sex, smoking, alcohol use, physical activity, nutrition, prevalent coronary heart disease, chronic kidney disease, diabetes, and hypertension, we computed hazard ratios to examine the association between television viewing time (≤2 h/day, 2-4 h/day, and ≥4 h/day) and mortality. RESULTS: Participants had a mean age of 55 years, and 64% were women. After a median follow-up of 9.9 years (interquartile range, 9.0-10.7), 615 deaths occurred (data analysis conducted in 2017). Hazard ratios for mortality were 1.08 (0.86-1.37) for television time of 2 to 4 hours per day and 1.48 (95% CI: 1.19-1.83) for television time of greater than or equal to 4 hours per day when compared with those who watched television less than 2 hours per day (P trend = .002). When we restricted analyses to those who performed leisure-time activities, the hazard ratios for mortality were 1.10 (95% CI, 0.84-1.45) for television viewing of 2 to 4 hours per day and 1.45 (95% CI, 1.13-1.86) for more than 4 hours per day compared with the less than 2 hours per day. CONCLUSION: Our findings suggest that greater television viewing time, even among those who perform leisure-time physical activities, is associated with increased all-cause mortality among African Americans. Thus, it may serve as an indicator of a sedentary lifestyle with potential for intervention.

7.
Matern Child Health J ; 22(2): 204-215, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29119477

RESUMO

Objectives To examine pregnancy-related deaths (PRDs) in Florida, to identify quality improvement (QI) opportunities, and to recommend strategies aimed at reducing maternal mortality. Methods The Florida Pregnancy-Associated Mortality Review (PAMR) Committee reviewed PRDs occurring between 1999 and 2012. The PAMR Committee determined causes of PRDs, identified contributing factors, and generated recommendations for prevention and quality improvement. Information from the PAMR data registry, and live births from Florida vital statistic data were used to calculate pregnancy-related mortality ratios (PRMR) and PRD univariate risk ratios (RR) with 95% confidence intervals (CI). Results Between 1999 and 2012, the PRMR fluctuated between 14.7 and 26.2 PRDs per 100,000 live births. The five leading causes of PRD were hypertensive disorders (15.5%), hemorrhage (15.2%), infection (12.7%), cardiomyopathy (11.1%), and thrombotic embolism (10.2%), which accounted for 65% of PRDs. Principal contributing factors were morbid obesity (RR = 7.0, 95% CI 4.9-10.0) and late/no prenatal care (RR = 4.2, 95% CI 3.1-5.6). The PRMR for black women was three-fold higher (RR = 3.3, 95% CI 2.7-4.0) than white women. Among the five leading causes of PRDs, 42.5% had at least one clinical care or health care system QI opportunity. Two-third of these were associated with clinical quality of care, which included standards of care, coordination, collaboration, and communication. The QI opportunities varied by PRD cause, but not by race/ethnicity. Conclusion Gaps in clinical care or health care systems were assessed as the primary factors in over 40% of PRDs leading the PAMR Committee to generate QI recommendations for clinical care and health care systems.

8.
J Biomed Inform ; 75S: S120-S128, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28694118

RESUMO

OBJECTIVE: Our objective was to develop a machine learning-based system to determine the severity of Positive Valance symptoms for a patient, based on information included in their initial psychiatric evaluation. Severity was rated on an ordinal scale of 0-3 as follows: 0 (absent=no symptoms), 1 (mild=modest significance), 2 (moderate=requires treatment), 3 (severe=causes substantial impairment) by experts. MATERIALS AND METHODS: We treated the task of assigning Positive Valence severity as a text classification problem. During development, we experimented with regularized multinomial logistic regression classifiers, gradient boosted trees, and feedforward, fully-connected neural networks. We found both regularization and feature selection via mutual information to be very important in preventing models from overfitting the data. Our best configuration was a neural network with three fully connected hidden layers with rectified linear unit activations. RESULTS: Our best performing system achieved a score of 77.86%. The evaluation metric is an inverse normalization of the Mean Absolute Error presented as a percentage number between 0 and 100, where 100 means the highest performance. Error analysis showed that 90% of the system errors involved neighboring severity categories. CONCLUSION: Machine learning text classification techniques with feature selection can be trained to recognize broad differences in Positive Valence symptom severity with a modest amount of training data (in this case 600 documents, 167 of which were unannotated). An increase in the amount of annotated data can increase accuracy of symptom severity classification by several percentage points. Additional features and/or a larger training corpus may further improve accuracy.


Assuntos
Automação , Redes Neurais (Computação) , Humanos , Aprendizado de Máquina
9.
Circ Heart Fail ; 10(6)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28611127

RESUMO

BACKGROUND: African Americans develop chronic kidney disease and pulmonary hypertension (PH) at disproportionately high rates. Little is known whether PH heightens the risk of heart failure (HF) admission or mortality among chronic kidney disease patients, including patients with non-end-stage renal disease. METHODS AND RESULTS: We analyzed African Americans participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urine albumin/creatinine >30 mg/g) and available echocardiogram-derived pulmonary artery systolic pressure (PASP) from the Jackson Heart Study (N=408). We used Cox models to assess whether PH (PASP>35 mm Hg) was associated with higher rates of HF hospitalization and mortality. In a secondary, cross-sectional analysis, we examined the relationship between cystatin C (a marker of renal function) and PASP and potential mediators, including BNP (B-type natriuretic peptide) and endothelin-1. In our cohort, the mean age was 63±13 years, 70% were female, 78% had hypertension, and 22% had PH. Eighty-five percent of the participants had an estimated glomerular filtration rate >30 mL/min per 1.73 m2. During follow-up, 13% were hospitalized for HF and 27% died. After adjusting for potential confounders, including BNP, PH was found to be associated with HF hospitalization (hazard ratio, 2.37; 95% confidence interval, 1.15-4.86) and the combined outcome of HF hospitalization or mortality (hazard ratio, 1.84; confidence interval, 1.09-3.10). Log cystatin C was directly associated with PASP (adjusted ß =2.5 [95% confidence interval, 0.8-4.1] per standard deviation change in cystatin C). Mediation analysis showed that BNP and endothelin-1 explained 56% and 40%, respectively, of the indirect effects between cystatin C and PASP. CONCLUSIONS: Among African Americans with chronic kidney disease, PH, which is likely pulmonary venous hypertension, was associated with a higher risk of HF admission and mortality.


Assuntos
Afro-Americanos , Insuficiência Cardíaca/etiologia , Hipertensão Pulmonar/complicações , Insuficiência Renal Crônica/mortalidade , Idoso , Estudos Transversais , Ecocardiografia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etnologia , Humanos , Hipertensão Pulmonar/etnologia , Hipertensão Pulmonar/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Estudos Prospectivos , Pressão Propulsora Pulmonar , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
10.
PLoS One ; 12(5): e0177687, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28520820

RESUMO

INTRODUCTION: Although the US Preventive Services Task Force recommends against routine prostate cancer screening with prostate-specific antigen (PSA) testing, specialty organizations support screening via shared decision making between providers and selected patients. While discussions about advantages and disadvantages of testing are a feature of patient-centered care, it is unclear how provider recommendations and the presence of a personal doctor influence testing in the presence of such discussions. MATERIALS AND METHODS: We used the 2013 Behavioral Risk Factor Surveillance System to identify 1,737 male respondents surveyed about their PSA testing decisions. We describe the prevalence of provider recommendations and utilize weighted multivariable logistic regression models to examine the impact of provider recommendations and presence of a personal doctor on routine testing while accounting for patient-provider discussions about advantages and disadvantages. RESULTS: The majority (70.4%) of respondents reported some form of discussion with providers about testing and most underwent screening in accordance with provider recommendations. In multivariable analyses, men whose providers had never recommended PSA test were less likely to receive screening [OR 0.03, 95% CI (0.02-0.05)], and patients who did not identify a personal doctor in their care were less likely to undergo testing [OR 0.12, 95% CI (0.04-0.32)]. DISCUSSION: Provider recommendations and having a personal doctor are associated with routine PSA testing. These findings suggest that providers and policymakers should be aware of how the content and context of communication with patients, beyond discussions of risks and benefits, can influence routine PSA testing behaviors.


Assuntos
Detecção Precoce de Câncer/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Relações Médico-Paciente , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Idoso , Detecção Precoce de Câncer/normas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/psicologia
11.
Cancer Med ; 6(5): 1102-1107, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28378409

RESUMO

Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among women aged 40-89. A longitudinal repeated measures analysis estimated the proportion of DBT performed for screening or diagnostic indications over time and by insurance type. During the study period, 93,182 mammograms were performed on 48,234 women. Of these exams, 16,506 DBT tests were performed for screening (18.1%) and 2537 were performed for diagnosis (15.7%). Between 2011 and 2014, DBT utilization increased in all insurance groups. However, by the latest observed period, screening DBT was used more frequently under private insurance (43.4%) than Medicaid (36.2%), Medicare (37.8%), other (38.6%), or no insurance (32.9%; P < 0.0001). No sustained differences in use of DBT for diagnostic testing were seen by insurance type. DBT is increasingly used for breast cancer screening and diagnosis. Use of screening DBT may be associated with insurance type. Surveillance is required to ensure that disparities in breast cancer screening are minimized as DBT becomes more widely available.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Humanos , Seguro Saúde , Mamografia/estatística & dados numéricos , Medicaid , Medicare , Pessoa de Meia-Idade , Atenção Primária à Saúde , Estados Unidos
12.
JAMA Intern Med ; 177(6): 829-837, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28395014

RESUMO

Importance: National patterns of low-value and high-value care delivered to patients without insurance or with Medicaid could inform public policy but have not been previously examined. Objective: To measure rates of low-value care and high-value care received by patients without insurance or with Medicaid, compared with privately insured patients, and provided by safety-net physicians vs non-safety-net physicians. Design, Setting, and Participants: This multiyear cross-sectional observational study included all patients ages 18 to 64 years from the National Ambulatory Medical Care Survey (2005-2013) and the National Hospital Ambulatory Medical Care Survey (2005-2011) eligible for any of the 21 previously defined low-value or high-value care measures. All measures were analyzed with multivariable logistic regression and adjusted for patient and physician characteristics. Exposures: Comparison of patients by insurance status (uninsured/Medicaid vs privately insured) and safety-net physicians (seeing >25% uninsured/Medicaid patients) vs non-safety-net physicians (seeing 1%-10%). Main Outcomes and Measures: Delivery of 9 low-value or 12 high-value care measures, based on previous research definitions, and composite measures for any high-value or low-value care delivery during an office visit. Results: Overall, 193 062 office visits were eligible for at least 1 measure. Mean (95% CI) age for privately insured patients (n = 94 707) was 44.7 (44.5-44.9) years; patients on Medicaid (n = 45 123), 39.8 (39.3-40.3) years; and uninsured patients (n = 19 530), 41.9 (41.5-42.4) years. Overall, low-value and high-value care was delivered in 19.4% (95% CI, 18.5%-20.2%) and 33.4% (95% CI, 32.4%-34.3%) of eligible encounters, respectively. Rates of low-value and high-value care delivery were similar across insurance types for the majority of services examined. Among Medicaid patients, adjusted rates of use were no different for 6 of 9 low-value and 9 of 12 high-value services compared with privately insured beneficiaries, whereas among the uninsured, rates were no different for 7 of 9 low-value and 9 of 12 high-value services. Safety-net physicians provided similar care compared with non-safety-net physicians, with no difference for 8 out of 9 low-value and for all 12 high-value services. Conclusions and Relevance: Overuse of low-value care is common among patients without insurance or with Medicaid. Rates of low-value and high-value care were similar among physicians serving vulnerable patients and other physicians. Overuse of low-value care is a potentially important focus for state Medicaid programs and safety-net institutions to pursue cost savings and improved quality of health care delivery.


Assuntos
Acesso aos Serviços de Saúde/economia , Medicaid/economia , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Medicina/estatística & dados numéricos , Atenção Primária à Saúde/economia , Qualidade da Assistência à Saúde/economia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Cobertura do Seguro/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pobreza , Padrões de Prática Médica/economia , Estados Unidos , Adulto Jovem
14.
Genetics ; 204(3): 1075-1087, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27585844

RESUMO

The organization and stability of higher order structures that form in the extracellular matrix (ECM) to mediate the attachment of muscles are poorly understood. We have made the surprising discovery that a subset of clotting factor proteins are also essential for muscle attachment in the model organism Drosophila melanogaster One such coagulation protein, Fondue (Fon), was identified as a novel muscle mutant in a pupal lethal genetic screen. Fon accumulates at muscle attachment sites and removal of this protein results in decreased locomotor behavior and detached larval muscles. A sensitized genetic background assay reveals that fon functions with the known muscle attachment genes Thrombospondin (Tsp) and Tiggrin (Tig). Interestingly, Tig is also a component of the hemolymph clot. We further demonstrate that an additional clotting protein, Larval serum protein 1γ (Lsp1γ), is also required for muscle attachment stability and accumulates where muscles attach to tendons. While the local biomechanical and organizational properties of the ECM vary greatly depending on the tissue microenvironment, we propose that shared extracellular protein-protein interactions influence the strength and elasticity of ECM proteins in both coagulation and muscle attachment.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Proteínas Sanguíneas/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Músculo Esquelético/metabolismo , Tendões/metabolismo , Animais , Fatores de Coagulação Sanguínea/genética , Proteínas Sanguíneas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Hemolinfa/metabolismo , Músculo Esquelético/fisiologia , Ligação Proteica , Tendões/fisiologia , Trombospondinas/genética , Trombospondinas/metabolismo
15.
Am J Prev Med ; 51(4): 502-6, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27539974

RESUMO

INTRODUCTION: The epidemiology of American Heart Association ideal cardiovascular health (CVH) metrics has not been fully examined in African Americans. This study examines the associations of CVH metrics with incident cardiovascular disease (CVD) in the Jackson Heart Study, a longitudinal cohort study of CVD in African Americans. METHODS: Jackson Heart Study participants without CVD (n=4,702) were followed prospectively between 2000 and 2011. Incidence rates and Cox proportional hazard ratios estimated risks for incident CVD (myocardial infarction, stroke, cardiac procedures, and CVD mortality) associated with seven CVH metrics by sex. Analyses were performed in 2015. RESULTS: Participants were followed for a median of 8.3 years; none had ideal health on all seven CVH metrics. The prevalence of ideal health was low for nutrition, physical activity, BMI, and blood pressure metrics. The age-adjusted CVD incidence rate (IR) per 1,000 person years was highest for individuals with the least ideal health metrics: zero to one (IR=12.5, 95% CI=9.7, 16.1), two (IR=8.2, 95% CI=6.5, 10.4), three (IR=5.7, 95% CI=4.2, 7.6), and four or more (IR=3.4, 95% CI=2.0, 5.9). Adjusting for covariates, individuals with four or more ideal CVH metrics had lower risks of incident CVD compared with those with zero or one ideal CVH metric (hazard ratio, 0.29; 95% CI=0.17, 0.52; p<0.001). CONCLUSIONS: African Americans with more ideal CVH metrics have lower risks of incident CVD. Comprehensive preventive behavioral and clinical supports should be intensified to improve CVD risk for African Americans with few ideal CVH metrics.


Assuntos
Doenças Cardiovasculares/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia
16.
Hum Mol Genet ; 25(10): 1946-1964, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26931463

RESUMO

PINK1/Parkin-mediated mitochondrial quality control (MQC) requires valosin-containing protein (VCP)-dependent Mitofusin/Marf degradation to prevent damaged organelles from fusing with the healthy mitochondrial pool, facilitating mitochondrial clearance by autophagy. Drosophila clueless (clu) was found to interact genetically with PINK1 and parkin to regulate mitochondrial clustering in germ cells. However, whether Clu acts in MQC has not been investigated. Here, we show that overexpression of Drosophila Clu complements PINK1, but not parkin, mutant muscles. Loss of clu leads to the recruitment of Parkin, VCP/p97, p62/Ref(2)P and Atg8a to depolarized swollen mitochondria. However, clearance of damaged mitochondria is impeded. This paradox is resolved by the findings that excessive mitochondrial fission or inhibition of fusion alleviates mitochondrial defects and impaired mitophagy caused by clu depletion. Furthermore, Clu is upstream of and binds to VCP in vivo and promotes VCP-dependent Marf degradation in vitro Marf accumulates in whole muscle lysates of clu-deficient flies and is destabilized upon Clu overexpression. Thus, Clu is essential for mitochondrial homeostasis and functions in concert with Parkin and VCP for Marf degradation to promote damaged mitochondrial clearance.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Drosophila/genética , Proteínas de Membrana/genética , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinases/genética , Ubiquitina-Proteína Ligases/genética , Animais , Drosophila melanogaster/genética , Humanos , Mitocôndrias/genética , Degradação Mitocondrial/genética , Músculos/metabolismo , Músculos/patologia , Mutação , Proteólise , Proteína com Valosina
17.
Med Care ; 54(6): 555-61, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26974677

RESUMO

BACKGROUND: Monitoring political and social determinants of delayed or forgone care due to cost is necessary to evaluate efforts to reduce racial and ethnic disparities in access to care. Our objective was to examine the extent to which state Medicaid expansion decisions and personal household income may be associated with individual-level racial and ethnic disparities in delayed or forgone care due to cost, at baseline, before the implementation of the Affordable Care Act. METHODS: We used 2012 Behavioral Risk Factor Surveillance System survey data to examine racial and ethnic differences in delayed or forgone care due to cost in states that do and do not plan Medicaid expansion. We examined personal household income as a social factor that could contribute to racial and ethnic disparities in delayed or forgone care. RESULTS: We found that personal income differences were strongly related to disparities in delayed or forgone care in places with and without plans to expand Medicaid. In addition, while delayed or forgone care disparities between non-Hispanic whites and non-Hispanic blacks were lowest in places with plans to expand Medicaid access, disparities between non-Hispanic whites and Hispanics did not differ by state Medicaid expansion plans. CONCLUSIONS: As access to insurance improves for diverse groups, health systems must develop innovative strategies to overcome social determinants of health, including income inequities, as barriers to accessing care for Hispanic and non-Hispanic blacks. Additional efforts may be needed to ensure Hispanic groups achieve the benefits of investments in health care access.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Renda/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Adolescente , Adulto , Afro-Americanos/estatística & dados numéricos , Sistema de Vigilância de Fator de Risco Comportamental , Diagnóstico Tardio/economia , Diagnóstico Tardio/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Acesso aos Serviços de Saúde/economia , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/etnologia , Hispano-Americanos/estatística & dados numéricos , Humanos , Medicaid/economia , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
18.
Mitochondrion ; 26: 33-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26611999

RESUMO

Mitochondria are dynamic organelles that change their architecture in normal physiological conditions. Mutations in genes that control mitochondrial fission or fusion, such as dynamin-related protein (Drp1), Mitofusins 1 (Mfn1) and 2 (Mfn2), and Optic atrophy 1 (Opa1), result in neuropathies or neurodegenerative diseases. It is increasingly clear that altered mitochondrial dynamics also underlie the pathology of other degenerative diseases, including Parkinson's disease (PD). Thus, understanding mitochondrial distribution, shape, and dynamics in all cell types is a prerequisite for developing and defining treatment regimens that may differentially affect tissues. The majority of Drosophila genes implicated in mitochondrial dynamics have been studied in the adult indirect flight muscle (IFM). Here, we discuss the utility of Drosophila third instar larvae (L3) as an alternative model to analyze and quantify mitochondrial behaviors. Advantages include large muscle cell size, a stereotyped arrangement of mitochondria that is conserved in mammalian muscles, and the ability to analyze muscle-specific gene function in mutants that are lethal prior to adult stages. In particular, we highlight methods for sample preparation and analysis of mitochondrial morphological features.


Assuntos
Proteínas de Drosophila , Mitocôndrias Musculares , Proteínas Mitocondriais , Músculos , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Larva/genética , Larva/metabolismo , Larva/ultraestrutura , Mitocôndrias Musculares/genética , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/ultraestrutura , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Músculos/metabolismo , Músculos/ultraestrutura
19.
ACS Med Chem Lett ; 6(4): 439-44, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25893046

RESUMO

We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCR5. Installation of a γ-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

20.
Prev Med ; 74: 111-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25712326

RESUMO

OBJECTIVES: The aim of this study is to assess the prevalence and changes over time of ideal Life's Simple Seven (LSS) in African-Americans. METHODS: Prospective cohort of 5301 African-Americans from the Jackson Heart Study (JHS) from 2000 to 2013. Each of the LSS metrics was categorized as poor, intermediate, or ideal. RESULTS: Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal LSS was 3.3%, 23.0%, 33.5%, 24.7%, 11.6%, 3.6%, 0.3%, and 0%, respectively. Corresponding values for women were 1.7%, 26.3%, 33.1%, 22.8%, 11.9%, 3.7%, 0.6%, and 0%. Prevalence of ideal diet was 0.9%. The proportions of those meeting LSS ideal recommendations for cholesterol and fasting glucose declined from the first through third JHS visits across all age groups, whereas prevalence of ideal BMI declined only in participants <40 years at a given visit. Prevalence of ideal blood pressure did not change over time and being ideal on physical activity improved from the first [18.3% (95% CI: 17.3% to 19.3%)] to third visit [24.8% (95% CI: 23.3% to 26.3%)]. CONCLUSIONS: Our data show a low prevalence of ideal LSS (especially diet, physical activity, and obesity) in the JHS and a slight improvement in adherence to physical activity recommendations over time.


Assuntos
Afro-Americanos/estatística & dados numéricos , Doenças Cardiovasculares/etnologia , Comportamentos Relacionados com a Saúde/etnologia , Hipertensão/complicações , Atividade Motora/fisiologia , Obesidade/complicações , Adulto , Idoso , Glicemia/análise , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Dieta/efeitos adversos , Dieta/etnologia , Dieta/estatística & dados numéricos , Feminino , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Avaliação Nutricional , Obesidade/etnologia , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/classificação , Prevalência , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Fatores Socioeconômicos
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