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OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide spectrum of clinical manifestations. A decision aid (DA) for SLE was developed and implemented in 15 rheumatology clinics throughout the United States. This study explored the experiences of patients who viewed the DA to understand how patients engage with and respond to the SLE DA. METHODS: We conducted a qualitative descriptive study using semistructured interviews with a convenience sample of 24 patients during May to July 2022. RESULTS: Patients recognized the value of the SLE DA in providing general knowledge about SLE and different treatment options. However, patients expressed a desire for more comprehensive lifestyle information to better manage their condition. Another theme was the importance of having multiple formats available to cater to their different needs, as well as tailoring the DA to different stages of SLE. CONCLUSION: This study contributes to a broader understanding of how to provide patient-centered care for patients with SLE by offering practical insights that can inform the development of more effective, patient-centric health information technologies for managing chronic diseases, ultimately improving patient outcomes. Overall, this study underscores the significance of optimizing both the information content and determining the appropriate delivery of the tool for its future sustainability.
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Técnicas de Apoio para a Decisão , Lúpus Eritematoso Sistêmico , Participação do Paciente , Pesquisa Qualitativa , Humanos , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/psicologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente , Idoso , Estados Unidos , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Federally Qualified Health Centers (FQHCs) are pivotal in delivering healthcare services to underserved populations in the United States. While the number of FQHCs and FQHC look-alikes has been increasing, intensifying competition, limited research has examined the cost implications associated with this growing competition among FQHCs. This study aims to fill the research gap by analyzing the relationship between the level of competition among FQHCs and the cost of care per patient. Understanding this relationship is crucial for managers and policymakers in deriving informed decisions related to the expansion of FQHCs. The study comprehensively analyzed data from FQHCs from 2016 to 2022. The analysis involved examining the cost per patient in relation to the level of FQHC competition, measured by FQHC saturation in the area. The study's findings reveal a positive association between FQHC competition and the cost of care. Specifically, FQHCs in areas with higher levels of FQHC competition reported a higher cost per patient. This relationship underscores the potential financial dynamics influenced by the competitive environment among FQHCs. The results of this study have important implications for healthcare management and policy formulation. FQHC managers are suggested to consider the cost implications of increased competition in their strategic planning and operations. Meanwhile, policymakers should consider the potential cost ramifications of FQHC competition when designing and implementing policies related to FQHC expansion, especially those aimed at optimizing resource allocation and ensuring care affordability. Recognizing the impact of competition on cost can lead to more informed decisions regarding the funding, establishment, and distribution of FQHCs, ultimately contributing to the sustainability and efficacy of healthcare services in underserved areas.
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INTRODUCTION: A software program was developed to provide visual, guided feedback to students for access cavity preparations in preclinical learning. The specific aim of the study was to investigate students' overall experiences with the new learning method and compare their experiences with traditional teaching. MATERIALS AND METHODS: A workflow based on freely available software was designed to interactively register three-dimensional models of molars with access cavities, and to metrically compare these to instructor-prepared standard cavities. Third-year students practicing molar endodontics access cavity preparation in the preclinical course were then surveyed. A total of 44/79 students completed self-administered questionnaires prior and after the use of the feedback software to gauge their learning experience. RESULTS: The results of the post-training questionnaire illustrated that all surveyed students agreed/strongly agreed that the software assisted their learning in access cavity preparation. In addition, 86 and 89%, respectively, of students agreed that the use of the software improved their skills of access cavity preparation and felt more confident about their access cavity preparation skills after using the software package, 3D Dental Align. DISCUSSION: The presented software solution permitted setting and comparing access cavity preparations by students against a standard access prepared by an instructor. The process of data acquisition and registration was fast and straightforward. Student feedback was very positive and suggested the integration of this type of experiential learning into the preclinical curriculum. CONCLUSION: This feasibility study demonstrated the utility of the new technology to assist dental students' access cavity preparation learning.
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Avaliação Educacional , Endodontia , Humanos , Retroalimentação , Avaliação Educacional/métodos , Estudantes de Odontologia , Educação em Odontologia/métodos , Software , Endodontia/educaçãoRESUMO
BACKGROUND: Federally qualified health centers (FQHCs) are pivotal safety net primary care providers for the medically underserved. FQHCs have complex organizational designs, with many FQHCs providing care at multiple physical locations ("sites"). The number of sites, however, varies considerably between FQHCs, which can have important implications for differential access that may perpetuate disparities in quality of care. PURPOSE: The objective of this study is to explore the organizational and environmental antecedents of the number of sites operated by each FQHC. The findings of this study contribute to a better understanding of FQHCs' expansion that has vital implications for cost and access outcomes. METHODOLOGY/APPROACH: The study is based on data between the years 2012 and 2018. Using multivariate growth curve modeling, we analyzed the final sample, consisting of 5,482 FQHC-years. RESULTS: The level of competition, measured as the number of FQHC sites in the Primary Care Service Area (PCSA) and the number of primary care physicians per 1,000 PCSA residents, was positively associated with the number of FQHC sites. The number of patients, the level of federal grant, and the year were also positively associated with the number of FQHC sites, whereas percentage of Medicaid patients; workforce supply, measured as primary care physician assistants per 1,000 PCSA residents; Medicaid expansion; and state/local funding available for FQHCs were not. CONCLUSION: Findings of this study indicate that competition, especially between peer FQHCs, is significantly associated with FQHC expansion. PRACTICE IMPLICATIONS: This result suggests that FQHC managers and policymakers may closely monitor cost, access, and quality implications of competition and FQHC expansion.
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Acessibilidade aos Serviços de Saúde , Provedores de Redes de Segurança , Humanos , Medicaid , Estados UnidosRESUMO
OBJECTIVE: Patient engagement using health information technology (IT) functionalities can be a powerful tool in managing their own care for better health outcomes. Therefore, this study explores whether patient engagement IT functionalities and electronic health record (EHR) can affect patient safety outcomes. DESIGN: Using longitudinal study design for general acute care hospitals within the United States, we examine the interaction effects of EHR and patient engagement IT functionalities on patient safety outcomes (adverse incident rate) using a generalized estimating equation. SETTING: Our national sample consisted of 9759 hospital-year observations from 2014 to 2018. Overall, we found a significant association between adverse incident rate and patient engagement level and EHR adoption level. RESULTS: On average, as the combined effects of patient engagement level and EHR adoption level increases, the adverse incident rate decreases by approximately 0.49 (P < .01). Incorporating patient engagement functionalities is becoming an essential tool to improve health outcomes and will play an instrumental role in meeting meaningful use standards. CONCLUSIONS: Our study provides insights into the potential synergy between a hospital's existing EHR maturity and patient engagement health IT functionalities in affecting organizational performance. Organizational culture and capabilities pertinent to adopting patient engagement health IT functionalities infrastructure should be established first to provide the impetus for this synergy.
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Participação do Paciente , Segurança do Paciente , Registros Eletrônicos de Saúde , Hospitais , Humanos , Estudos Longitudinais , Uso Significativo , Estados UnidosRESUMO
BACKGROUND AND OBJECTIVES: Health information technology (HIT) for patient-engagement can positively influence the quality and efficiency of health care delivery. Although this topic is of significant importance, it has not been fully addressed in the federally qualified health center (FQHC) context. This research investigates the relationship between the level of patient-engagement HIT and FQHC preventive health care quality outcomes. METHOD: Based on the Uniform Data System (UDS), this study employed multivariable regression analysis to investigate the association between the level of patient-engagement HIT and FQHC preventive health care quality outcomes. FQHCs were placed in 4 mutually exclusive groups based on the level of FQHC use of patient-engagement HIT. RESULTS: The results indicate that compared with the most comprehensive patient-engagement HIT at FQHCs, less comprehensive patient-engagement HIT was associated with lower rates of preventive care provision. CONCLUSIONS: Comprehensive patient-engagement HIT across FQHCs may improve preventive health care quality outcomes. The results support policy incentives for FQHCs with less comprehensive levels of patient-engagement HIT to foster improved preventive care for their patients.
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Federally Qualified Health Centers (FQHCs) are ideally positioned to identify and address health-related social needs, but little is understood about the relationship between social risk factor (SRF) screening and health outcomes. We studied 1352 FQHCs from the 2019 Uniform Data System. Ordinary least squares regression was used to estimate the relationship between SRF screening and the percentage of patients with adequately controlled diabetes and hypertension. Results show 71% of the FQHCs in the sample collected SRFs. FQHCs' screened for SRFs had higher percentages of patients with adequately controlled diabetes (69.5% vs 67.0%, P < .001) and hypertension (63.8% vs 59.4%, P < .001) relative to FQHCs not collecting SRFs.
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Diabetes Mellitus , Humanos , Fatores de Risco , Feminino , Masculino , Pessoa de Meia-Idade , Estados Unidos , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Programas de Rastreamento , Determinantes Sociais da Saúde , Adulto , Provedores de Redes de Segurança , Idoso , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Dodecamethylcyclohexasiloxane (D6) is a siloxane substance mainly used in cosmetics and personal care products. While octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were once commonly used in personal care products, their usage has been restricted due to the classification as persistent, bioaccumulative, and toxic (PBT)/very persistent and very bio-accumulative (vPvB) substances. While D6 has emerged as a substitute for D4 and D5, the risk assessment for D6 remains limited compared to the evaluations for D4 and D5. To address this gap, we conducted a comprehensive risk assessment of D6. In this study, we reviewed the toxicity information on D6 and calculated the exposure level to D6, considering the content of D6 in cosmetic products. No observed adverse effect level (NOAEL) of 1500 mg/kg bw/day was established in a repeated dose toxicity study after oral administration to rats. Negative results were found in tests on the ocular and skin irritation, skin sensitization, and genotoxicity of D6. According to the product content of up to 48% of D6 reported in 2012, the Systemic Exposure Dose (SED) was 5.4E-06 to 7.04 mg/kg bw/day for a 60 kg adult using the exposure factors from Korean cosmetic usage. The Margin of Safety was estimated to be between 35.5 and 4.63E+07, posing a potential health risk of D6 according to the maximum concentration and the product type. Further consideration of the potential of D6 as PBT or vPvB is also required.
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Dosimetry modeling and point of departure (POD) estimation using in vitro data are essential for mechanism-based hazard identification and risk assessment. This study aimed to develop a putative adverse outcome pathway (AOP) for humidifier disinfectant (HD) substances used in South Korea through a systematic review and benchmark dose (BMD) modeling. We collected in vitro toxicological studies on HD substances, including polyhexamethylene guanidine hydrochloride (PHMG-HCl), PHMG phosphate (PHMG-p), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), CMIT, and MIT from scientific databases. A total of 193 sets of dose-response data were extracted from 34 articles reporting in vitro experimental results of HD toxicity. The risk of bias (RoB) in each study was assessed following the office of health assessment and translation (OHAT) guideline. The BMD of each HD substance at different toxicity endpoints was estimated using the US Environmental Protection Agency (EPA) BMD software (BMDS). Interspecies- or interorgan differences or most critical effects in the toxicity of the HD substances were analyzed using a 95% lower confidence limit of the BMD (BMDL). We found a critical molecular event and cells susceptible to each HD substance and constructed an AOP of PHMG-p- or CMIT/MIT-induced damage. Notably, PHMG-p induced ATP depletion at the lowest in vitro concentration, endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), inflammation, leading to fibrosis. CMIT/MIT enhanced mitochondrial reactive oxygen species (ROS) production, oxidative stress, mitochondrial dysfunction, resulting in cell death. Our approach will increase the current understanding of the effects of HD substances on human health and contribute to evidence-based risk assessment of these compounds.
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OBJECTIVE: This paper aims to address the relationship between the community health center (CHC) patient mix and the level of patient engagement health information technology (HIT) comprehensiveness. PARTICIPANTS: The study was conducted on sample CHCs (n = 3,592 CHC-years) active between 2016 and 2018. METHODS: Patient engagement HIT comprehensiveness was measured based on a framework of patient engagement through HIT that includes a two-part dichotomy of patient engagement and patient informing. Univariate analysis was used to describe CHC characteristics and multivariable ordered logistic regression analysis was used to test hypothesized relationships. RESULTS: The study identified four levels of patient engagement HIT comprehensiveness: 1) to neither engage nor inform, 2) to primarily inform, 3) to primarily engage, and 4) to engage and inform. It was found that CHCs serving disproportionate shares of patients with disadvantageous socioeconomic characteristics are less likely to incorporate more comprehensive patient engagement HIT. CONCLUSION: The results highlight the different levels of patient engagement HIT use among CHCs and a negative association between CHC's higher proportion of patients with a disadvantageous sociodemographic background and patient engagement HIT comprehensiveness.
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Centros Comunitários de Saúde , Informática Médica , Humanos , Fatores SocioeconômicosRESUMO
This study examined whether an association exists between federally qualified health centers' (FQHCs') provision of medical training programs and clinical outcomes. Employing a cross-sectional data analysis of the sample FQHCs in the year 2019, the study found that FQHCs with medical training programs provided higher rates of immunization, screenings for cervical cancer, tobacco, statin use, and colorectal cancer. The FQHCs with medical training programs also reported a higher percentage of hypertensive patients properly managing blood pressure level. The results indicated that an FQHC providing medical training, as part of its organizational structure, may have a positive influence on patient outcomes.
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Capacitação em Serviço , Garantia da Qualidade dos Cuidados de Saúde , Humanos , Estudos Transversais , Estados Unidos , Instalações de SaúdeRESUMO
BACKGROUND: The Black Lives Matter movement and COVID-19 pandemic motivated the wide-scale adoption of diversity, equity, inclusion, and belonging (DEIB) initiatives within healthcare organizations and the creation of DEIB top-level leader positions. The next step is to understand how these leaders contribute to the implementation of DEIB interventions, a task with notable salience due to not only the historical difficulties associated with DEIB strategy execution, but also the substantial evidence that leadership plays a significant role in implementation processes. Therefore, the objective of this qualitative study is to understand the role of top-level DEIB leaders in the implementation of healthcare organizational DEIB interventions. METHODS: A qualitative research approach which used an in-depth semi-structured interview approach was employed. We conducted thirty-one 60-90-min semi-structured interviews with DEIB top-level leaders between February 2022 and October 2022 over Zoom. An iterative coding process was used to identify the key implementation strategies and activities of DEIB top-level leaders. RESULTS: Interviewees were mostly Black, majority female, and mostly heterosexual and had a variety of educational backgrounds. We identified the DEIB top-level leader as the DEIB strategy implementation champion. These leaders drive five DEIB implementation strategies: (1) People, (2) Health Equity, (3) Monitoring and Feedback, (4) Operational Planning and Communication, and (5) External Partners. Within these, we identified 19 significant activities that describe the unique implementation strategies supported by the DEIB top-level leaders. CONCLUSIONS: To move toward sustained commitment to DEIB, the organization must focus on not only establishing DEIB interventions, but on their successful implementation. Our findings help explicate the implementation activities that drive the DEIB initiatives of healthcare organizations and the role of DEIB leaders. Our work can help healthcare organizations systematically identify how to support the success of DEIB organizational interventions.
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Diversidade, Equidade, Inclusão , Pandemias , Humanos , Feminino , Pesquisa Qualitativa , Atenção à Saúde , LiderançaRESUMO
So-called "geographic expansion race," health care organizations expand physical facilities to different geographical locations as a way to foster growth. This study furthers knowledge on Federally Qualified Health Centers' (FQHCs') geographical expansion in relation to the local market's payer mix. The results indicated that areas with a higher proportion of Medicaid patients with fewer uninsured are more likely to see new FQHC sites opening. The findings are consistent with previous literature on the health care organization's geographical expansion and also indicated that some areas might lack proper FQHC services despite the high needs.
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Prática de Grupo , Pessoas sem Cobertura de Seguro de Saúde , Assistência Ambulatorial , Acessibilidade aos Serviços de Saúde , Humanos , Medicaid , Políticas , Estados UnidosRESUMO
ABSTRACT: The lesbian, gay, bisexual, transgender, and queer (LGBTQ) population deals with complex medical and behavioral issues coupled with barriers in accessing both healthcare and health insurance leading to poorer health outcomes as compared with the general population. Because this community is often overlooked in efforts to improve minority health disparities, in 2007, the Human Rights Campaign Foundation introduced the Healthcare Equality Index (HEI) for evaluating healthcare facilities' policies and practices related to the equity and inclusion of their LGBTQ patients, visitors, and employees. This study's aim was to determine whether the LGBTQ Healthcare Equality Leader institution designation advantage found by DiLeo et al (2020) has a continuing positive effect on Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) performance. We found that patient scores for both Overall Rating and Willingness to Recommend were higher with noted improvement for HEI Leader institutions as compared with non-HEI Leader institutions over this study's 3-year period. Based on the findings of this study, it can be implied that hospitals do receive a return on their investment for achieving or maintaining the HEI Leader designation and this investment benefits all populations served by the organization inferred by their maintained higher patient experience scores.
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Minorias Sexuais e de Gênero , Atenção à Saúde , Feminino , Hospitais , Humanos , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
Muc1 is a heterodimeric mucin that is expressed on the apical surface of airway epithelial cells as well as hematopoietic cells. Both in vivo and in vitro studies revealed that Muc1 suppresses inflammatory responses induced by Pseudomonas aeruginosa (PA). In this study, we sought to determine, using intact animals (C57BL/6 mice), whether the expression of Muc1 is important during airway PA infection, and how Muc1 levels are controlled during inflammation. Our results showed that: (1) Muc1 levels in the wild-type (WT) mice were initially low, but gradually increased after PA inhalation, reaching a peak on Day 2, remaining elevated until Day 4, and then gradually decreasing to basal levels on Day 7; (2) TNF receptor 1(-/-) mice failed to increase Muc1 levels after PA infection; (3) after PA inhalation, more inflammatory cells were present in the bronchoalveolar lavage fluid from either Muc1(-/-) or TNF receptor(-/-) mice compared with their WT control animals; (4) more apoptotic neutrophils were present in bronchoalveolar lavage fluid from WT mice compared with Muc1(-/-) mice. We conclude that Muc1(-/-) mice are more inflammatory than WT mice during airway PA infection as a result of both an increase in neutrophil influx and a decrease in neutrophil apoptosis. These results suggest that the up-regulation of Muc1 during airway PA infection might be crucial for suppressing excessive and prolonged inflammatory responses, and is induced mainly by TNF-α, the key proinflammatory mediator.
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Mucina-1/imunologia , Mucina-1/metabolismo , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa , Infecções Respiratórias/imunologia , Infecções Respiratórias/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Apoptose , Carga Bacteriana , Sequência de Bases , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucina-1/genética , Neutrófilos/imunologia , Neutrófilos/patologia , Infecções por Pseudomonas/microbiologia , RNA Mensageiro/genética , Receptores Tipo I de Fatores de Necrose Tumoral/deficiência , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologiaRESUMO
PURPOSE: The objective of this research is to synthesize evidence on the relationship between context, strategies and performance in the context of federally qualified health centers (FQHCs), a core safety net health services provider in the United States. The research also identifies prior approaches to measure contextual factors, FQHC strategy and performance. Gaps in the research are identified, and directions for future research are provided. DESIGN/METHODOLOGY/APPROACH: A systematic review of peer-reviewed journal articles published between the years 1997 and 2017 was conducted using a bibliographic search of PubMed, Business Source Premier and ABI/Inform databases. FINDINGS: 28 studies were selected for the analysis. Results supported associations among contextual factors (organizational and environmental) and FQHC strategy and FQHC performance. The research also indicates that previous research was primarily emphasized on clinical performance with less focus on other types of FQHC performance. In addition, there exists a wide variability in terms of measuring context, FQHC strategy and performance. ORIGINALITY/VALUE: Operating in resource-scarce and highly constraining environments, FQHCs have demonstrated the ability to stay innovative and competent as serving often unhealthier and costlier patient populations. To date, there has been no study that reviewed the relationships between context, FQHC strategy and FQHC performance. In addition, there is an absence of consensus on how context, FQHC strategy and FQHC performance are measured. This study is the first that examined context-strategy-performance relationships in the context of FQHCs.
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Eficiência Organizacional , Provedores de Redes de Segurança/organização & administração , Provedores de Redes de Segurança/normas , Estados UnidosRESUMO
A unique thermostable amylosucrase from Bifidobacterium thermophilum was produced as a recombinant protein with the half-life of 577 h at 50 °C. By adding 1.0 M fructose, turanose yield was improved from 22.7% to 43.3% with 1.0 M sucrose, and from 23.7% to 39.4% with 1.5 M sucrose. Sucrose consumption rate was greatest at 55 °C, but the lowest amount of turanose was produced. Thus, turanose yield from sucrose biomass was inversely proportional to reaction temperature and was highly dependent on [fructose]. Meanwhile, insoluble α-glucan yield was clearly reduced as [fructose] increased. With 1.0 M fructose + 1.0 M sucrose, glucan byproduct yield significantly decreased from 29.4% to 1.1%. Molecular weights of linear glucans were almost identical among various [sucrose]s and were homogenous with very low polydispersity. This unique dual reaction patterns of amylosucrase enzyme would be very useful for massive productions of two different biomaterials simply by changing sucrose biomass concentration.
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Proteínas de Bactérias/química , Dissacarídeos/síntese química , Glucanos/síntese química , Glucosiltransferases/química , Sacarose/química , Edulcorantes/síntese química , Bifidobacterium/enzimologia , Frutose/química , Glucosiltransferases/isolamento & purificação , Concentração de Íons de Hidrogênio , Estabilidade Proteica , Proteínas Recombinantes/química , TemperaturaRESUMO
Using an established high-performance liquid chromatography (HPLC) method based on anion exchange chromatography, fraction collection, and electrochemical detection, the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OH-dG) can be analyzed rapidly and precisely in human urine samples. In addition, by ultraviolet (UV) detection, it was shown recently that it is possible to simultaneously analyze creatinine and 7-methylguanine (m(7)Gua), an RNA degradation product, in urine. By adding a fluorescence detector to the HPLC system, we now report that it is also possible to detect pteridins such as neopterin and biopterin. The fluorescence detection was evaluated in detail for neopterin, an immune response and tumor marker. The urinary content of neopterin, assessed by using the HPLC method, was verified with a commercial neopterin enzyme-linked immunosorbent assay (ELISA) kit as indicated by the high correlation between the two methods (r=0.98). In urinary samples from 58 young healthy individuals (male and female nonsmokers, ages 19-39 years), it was found that there was no significant correlation (r=-0.04) between the levels of 8-OH-dG and neopterin (as normalized to urinary creatinine levels). In contrast, in urinary samples from 60 old healthy individuals (male and female nonsmokers, ages 60-86 years), there was a significant correlation (r=0.47) found between the levels of 8-OH-dG and neopterin (as normalized to urinary creatinine levels). These findings strongly indicate that the higher level of immune response that was correlating with old age contributes significantly to the higher level of oxidative damage as assessed in the form of 8-OH-dG. Using this type of HPLC system, it is possible to evaluate oxidative DNA damage and immune response simultaneously using the respective urinary markers. These data may contribute to understanding of the pathophysiology of diseases such as infections and tumor progression where both oxidative stress and immune response occur simultaneously.
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Envelhecimento/imunologia , Envelhecimento/urina , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Neopterina/imunologia , Neopterina/urina , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Automação , Cromatografia Líquida de Alta Pressão , Desoxiguanosina/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Recently, we observed that 8-hydroxyguanosine triphosphate and 8-hydroxy-2'-deoxyguanosine (oh(8)dG) inactivate Rac and consequently down-regulate the Rac-linked NADPH oxidase, iNOS, and Cox2. Based on these observations, we tested whether oh(8)dG has anti-inflammatory activity in vivo in lipopolysaccharide (LPS)-treated mice. LPS (1 mg/kg, ip)-treated mice exhibit marked inflammatory responses, including increases in proinflammatory cytokines (TNF-alpha, IL-6, IL-18, and IL-12p70) in serum and infiltration of neutrophils, increased translocation of NF-kappaB p50 from the cytosol to the nucleus, and phosphorylation of c-Jun in lung tissues. Mice were pretreated with oh(8)dG (up to 60 mg/kg, ip) 4 h before LPS injection, and this pretreatment dose-dependently inhibited the inflammatory responses; the inhibitions observed with 60 mg/kg oh(8)dG were statistically significant. At the same time, oh(8)dG pretreatment inactivated Rac in lung tissues. Oh(8)dG pretreatment (50 mg/kg, ip) also significantly protected against LPS-induced septic death. Furthermore, oh(8)dG was more effective than acetyl salicylic acid in inhibiting these inflammatory responses. 8-Hydroxyguanosine also had some effect but was much weaker than oh(8)dG. The effects of normal nucleosides (dG, G, and A) were negligible or not significant. These results support an anti-inflammatory activity for oh(8)dG, which could be ascribed to its Rac-inactivating action.