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The formation of the vascular network is an intricate and complex process that is an obligate requirement during vertebrate development. The cardiovascular system is the first organ to develop and reach a functional state, which underscores the crucial role of the vasculature in the developing embryo. The development of the vasculature into highly branched conduits needs to occur in numerous sites and in precise patterns to supply oxygen and nutrients to the rapidly expanding tissue of the embryo. This process is mediated by the coordinated response of vascular endothelial and mural cells to the heterogeneous angiogenic cues provided by tissues and organs, whereas aberrant regulation and coordination of angiogenic signals during development result in lethality, impaired organ development, or disease states. This article reviews the essential signaling pathways required for establishment of the vertebrate vasculature with a major focus on a key regulatory factor, vascular endothelial growth factor (VEGF). We also discuss current knowledge of physiological angiogenic processes as well as their disruptions in pathological processes, particularly tumorigenesis.
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Sistema Cardiovascular , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Osso e Ossos/irrigação sanguínea , Osso e Ossos/fisiologia , Sistema Cardiovascular/anatomia & histologia , Sistema Cardiovascular/crescimento & desenvolvimento , Sistema Cardiovascular/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Isoformas de Proteínas/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Reprodução , CicatrizaçãoRESUMO
Children of color are more likely to have poor sleep health than White children, placing them at risk for behavioral problems in the classroom and lower academic performance. Few studies, however, have utilized standardized measures of both classroom behavior and achievement. This study examined whether children's sleep (parent and teacher report) in first grade concurrently related to independent observations of classroom behavior and longitudinally predicted achievement test scores in second grade in a sample of primarily Black (86%) children (n = 572; age = 6.8) living in historically disinvested neighborhoods. Higher teacher-reported child sleepiness was associated with lower adaptive behaviors and higher problem behaviors in the classroom, and predicted lower achievement. Parent-reported bedtime resistance and disordered breathing also predicted lower achievement.
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Logro , Características de Residência , Adaptação Psicológica , Criança , Comportamento Infantil , Humanos , SonoRESUMO
BACKGROUND: The influence of social media among adolescent peer groups can be a powerful change agent. OBJECTIVE: Our scoping review aimed to elucidate the ways in which social media use among adolescent peers influences eating behaviors. METHODS: A scoping review of the literature of articles published from journal inception to 2019 was performed by searching PubMed (ie, MEDLINE), Embase, CINAHL, PsycINFO, Web of Science, and other databases. The review was conducted in three steps: (1) identification of the research question and clarification of criteria using the population, intervention, comparison, and outcome (PICO) framework; (2) selection of articles from the literature using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines; and (3) charting and summarizing information from selected articles. PubMed's Medical Subject Headings (MeSH) and Embase's Emtree subject headings were reviewed along with specific keywords to construct a comprehensive search strategy. Subject headings and keywords were based on adolescent age groups, social media platforms, and eating behaviors. After screening 1387 peer-reviewed articles, 37 articles were assessed for eligibility. Participant age, gender, study location, social media channels utilized, user volume, and content themes related to findings were extracted from the articles. RESULTS: Six articles met the final inclusion criteria. A final sample size of 1225 adolescents (aged 10 to 19 years) from the United States, the United Kingdom, Sweden, Norway, Denmark, Portugal, Brazil, and Australia were included in controlled and qualitative studies. Instagram and Facebook were among the most popular social media platforms that influenced healthful eating behaviors (ie, fruit and vegetable intake) as well as unhealthful eating behaviors related to fast food advertising. Online forums served as accessible channels for eating disorder relapse prevention among youth. Social media influence converged around four central themes: (1) visual appeal, (2) content dissemination, (3) socialized digital connections, and (4) adolescent marketer influencers. CONCLUSIONS: Adolescent peer influence in social media environments spans the spectrum of healthy eating (ie, pathological) to eating disorders (ie, nonpathological). Strategic network-driven approaches should be considered for engaging adolescents in the promotion of positive dietary behaviors.
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Mídias Sociais , Adolescente , Gerenciamento de Dados , Dieta Saudável , Comportamento Alimentar , Humanos , Influência dos Pares , Estados UnidosRESUMO
PURPOSE OF REVIEW: In this current review, we describe the benefits of community-based and "precision and personalized population health" (P3H) approaches to assessing and addressing sleep health problems and sleep-related cardiovascular diseases (CVD) among vulnerable populations such as racial/ethnic minorities, the elderly, and the socioeconomically disadvantaged. RECENT FINDINGS: Very few sleep health programs utilize a community-based or P3H approach, which may account for low estimates of sleep health problems, related CVD outcomes, and inadequate healthcare infrastructure to address sleep-related health outcomes at the community and population level. We describe community-based and P3H approaches and programs as solutions to accurately capture estimates of sleep health and reduce burden of sleep health problems and corollary CVD outcomes at the level of the community and population. Specifically, we describe seven critical steps needed to successfully implement a community-based and P3H approach to address sleep health problems. Community-based and P3H approaches are effective strategies to assessing and addressing sleep health problems and related health conditions.
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Doenças Cardiovasculares , Hipertensão , Saúde da População , Idoso , Doenças Cardiovasculares/prevenção & controle , Etnicidade , Humanos , Grupos MinoritáriosRESUMO
Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b(+)Gr1(+) myeloid cells and has been implicated in resistance to anti-VEGF therapy in mouse models. High G-CSF production has been associated with a poor prognosis in cancer patients. Here we show that activation of the RAS/MEK/ERK pathway regulates G-CSF expression through the Ets transcription factor. Several growth factors induced G-CSF expression by a MEK-dependent mechanism. Inhibition of G-CSF release with a MEK inhibitor markedly reduced G-CSF production in vitro and synergized with anti-VEGF antibodies to reduce CD11b(+)Ly6G(+) neutrophil mobilization and tumor growth and led to increased survival in animal models of cancer, including a genetically engineered mouse model of pancreatic adenocarcinoma. Analysis of biopsies from pancreatic cancer patients revealed increased phospho-MEK, G-CSF, and Ets expression and enhanced neutrophil recruitment compared with normal pancreata. These results provide insights into G-CSF regulation and on the mechanism of action of MEK inhibitors and point to unique anticancer strategies.
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Fator Estimulador de Colônias de Granulócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Neutrófilos/citologia , Proteína Proto-Oncogênica c-ets-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Camundongos Transgênicos , Neoplasias/metabolismo , Neovascularização Patológica , Infiltração de Neutrófilos , Proteínas Tirosina Quinases/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
A large body of research has documented racial/ethnic disparities in childhood obesity in the United States (US) but less work has sought to understand differences within racial groups. Longitudinal studies are needed to describe BMI trajectories across development, particularly for Black children from immigrant families who have been underrepresented in childhood obesity research. The current study utilizes BMI data collected longitudinally from ages 5 to 8 years and growth mixture modeling to (1) identify and visualize growth patterns among Black children from primarily Caribbean immigrant families, and (2) to compare these patterns to growth trajectories among Black children from US-born families. First, we identified four classes or trajectories of growth for Black children from immigrant families. The largest trajectory (70% of the sample) maintained non-overweight throughout the study period. A second trajectory developed overweight by age 8 (25%). Two small trajectory groups demonstrated high rates of moderate and severe obesity-i.e., specifically, a trajectory of accelerated weight gain ending in moderate/severe obesity (3%), and a trajectory of early severe obesity with BMI decreasing slightly with age (2%). We identified a very similar four class/trajectory model among Black children from US-born families, and compared the model to the one for children from immigrant families using multi-group growth mixture modeling. We found that the patterns of growth did not differ significantly between the populations, with two notable exceptions. Among Black children from immigrant families, â¼ 5% were classified into the two heavier BMI trajectories, compared to â¼ 11% of children from US-born families. Additionally, among children with an accelerated weight gain trajectory, children from immigrant families had lower BMIs on average at each time point than children from US-born families. These findings describe the multiple trajectories of weight gain among Black children from immigrant families and demonstrate that although these trajectories are largely similar to those of Black children from US-born families, the differences provide some evidence for lower obesity risk among Black children from immigrant families compared to Black children from US-born families. As this study is the first to describe BMI trajectories for Black children from immigrant families across early and middle childhood, future work is needed to replicate these results and to explore differences in heavier weight trajectories between children from immigrant and US-born families.
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Negro ou Afro-Americano , Índice de Massa Corporal , Emigrantes e Imigrantes , Obesidade Infantil , Humanos , Emigrantes e Imigrantes/estatística & dados numéricos , Criança , Pré-Escolar , Masculino , Feminino , Obesidade Infantil/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Estados Unidos/epidemiologia , Estudos Longitudinais , Região do Caribe/etnologia , Fatores SocioeconômicosRESUMO
IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Estudos Transversais , Síndrome de COVID-19 Pós-Aguda , Progressão da Doença , Fatores de RiscoRESUMO
Inhibiting angiogenesis has become an important therapeutic strategy for cancer treatment but, like other current targeted therapies, benefits experienced for late-stage cancers can be curtailed by inherent refractoriness or by acquired drug resistance, requiring a need for better mechanistic understanding of such effects. Numerous preclinical studies have demonstrated that VEGF pathway inhibitors suppress primary tumour growth and metastasis. However, it has been recently reported that short-term VEGF and VEGFR inhibition can paradoxically accelerate tumour invasiveness and metastasis in certain models. Here we comprehensively compare the effects of both antibody and small molecule receptor tyrosine kinase (RTK) inhibitors targeting the VEGF-VEGFR pathway, using short-term therapy in various mouse models of metastasis. Our findings demonstrate that antibody inhibition of VEGF pathway molecules does not promote metastasis, in contrast to selected small molecule RTK inhibitors at elevated-therapeutic drug dosages. In particular, a multi-targeted RTK inhibitor, sunitinib, which most profoundly potentiated metastasis, also increased lung vascular permeability and promoted tumour cell extravasation. Mechanistically, sunitinib, but not anti-VEGF treatment, attenuated endothelial barrier function in culture and caused a global inhibition of protein tyrosine phosphorylation, including molecules important for maintaining endothelial cell-cell junctions. Together these findings indicate that, rather than a specific consequence of inhibiting the VEGF signalling pathway, pharmacological inhibitors of the VEGF pathway can have dose- and drug class-dependent side-effects on the host vasculature. These findings also advocate for the continued identification of mechanisms of resistance to anti-angiogenics and for therapy development to overcome it.
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Inibidores da Angiogênese/classificação , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/classificação , Antineoplásicos/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Anticorpos Monoclonais/uso terapêutico , Benzamidas , Benzenossulfonatos/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/uso terapêutico , Feminino , Mesilato de Imatinib , Técnicas In Vitro , Indóis/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piperazinas/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/imunologia , Sorafenibe , Sunitinibe , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
In TNF-treated cells, TNFR1, TNFR-associated death domain protein (TRADD), Fas-associated death domain protein, and receptor-interacting protein kinase proteins form the signaling complex via modular interaction within their C-terminal death domains. In this paper, we report that the death domain SXXE/D motifs (i.e., S381DHE motif of TNFR1-death domain as well as S215LKD and S296LAE motifs of TRADD-death domain) are phosphorylated, and this is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-κB. Phospho-S215LKD and phospho-S296LAE motifs are also critical to TRADD for recruiting Fas-associated death domain protein and receptor-interacting protein kinase. IκB kinase ß plays a critical role in TNFR1 phosphorylation of S381, which leads to subsequent T cell migration and accumulation. Consistently, we observed in inflammatory bowel disease specimens that TNFR1 was constitutively phosphorylated on S381 in those inflammatory T cells, which had accumulated in high numbers in the inflamed mucosa. Therefore, SXXE/D motifs found in the cytoplasmic domains of many TNFR family members and their adaptor proteins may serve to function as a specific interaction module for the α-helical death domain signal transduction.
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Movimento Celular/imunologia , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Fosfoproteínas/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Subpopulações de Linfócitos T/imunologia , Proteína de Domínio de Morte Associada a Receptor de TNF/metabolismo , Motivos de Aminoácidos/imunologia , Sequência de Aminoácidos , Animais , Epitopos de Linfócito T/imunologia , Células HEK293 , Humanos , Mediadores da Inflamação/fisiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Células Jurkat , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Fosfoproteínas/fisiologia , Fosforilação/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/fisiologia , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Proteína de Domínio de Morte Associada a Receptor de TNF/fisiologiaRESUMO
Introduction: Awareness, assessment and treatment of sleep apnea are disproportionately lower among Blacks, compared to other racial/ethnic groups. To address this health disparity gap, communication strategies that connect Blacks to OSA education, detection and treatment adherence interventions are needed. Strategies that engage individuals through communication technologies, community-level social network support, and medical providers in clinical settings are also needed. We present lessons learned from three studies that offer these solutions using a community-engaged research model: The Metabolic Syndrome Outcome Study (MetSO), Peer-enhanced Education to Reduce Sleep Ethnic Disparities (PEERS-ED), and Tailored Approach to Sleep Health Education (TASHE), to capture program effectiveness and lessons learned from project successes and failures. Methods: The methods of OSA community-based programs included the application of an OSA community-engaged research model. This model served as a strategic guideline for effective interventions to engage communities in research and ensure cultural appropriateness in OSA interventions. Focus groups, in-depth interviews and community steering committee meetings were conducted with various stakeholders. Delphi surveys were used to identify high priority diseases and conditions. Community barriers and needs were identified through iterative combinations of surveys and focus group meetings. Stakeholder groups participated in all aspects of our studies, including the development, dissemination and implementation phases, reflecting a bi-directional decision-making process that ensures the interests of both parties were considered. The MetSO, PEERS-ED and TASHE studies were reviewed to understand the effectiveness of the programs and to evaluate lessons learned. Results: MetSO, PEERS-ED and TASHE interventions revealed that community-engaged strategies are successful in enrolling Black populations into clinical trials. The study teams reached nearly 3,000 Blacks at risk of OSA and screened about 2,000 people in sleep apnea studies in New York City. Sleep brochures were distributed to over 10,000 people. Lessons learned from MetSO, PEERS-ED and TASHE interventions revealed that building relationships, establishing trust, identifying a study champion, learning to adjust and providing participant incentives are key strategic elements for successful recruitment and retention of Blacks participations in clinical trials. Conclusion: Strategic application of community-oriented frameworks ensures active community engagement throughout the research process, allowing for greater enrollment of Blacks in clinical studies as well as increased OSA awareness, diagnosis, and treatment.
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Reaching population-level impact for families in poverty requires moving beyond a sole focus on individuals, to a wider focus on interactions between individuals and their broader environmental contexts. Place-based initiatives have emerged as a policy response to promote community-level change around these broader interactions between individuals and their local communities through addressing long-standing disparities in housing, employment, education, and health. Together Growing Strong (TGS) is one such place-based initiative focused on transforming the health, wellbeing, and development of young children and their families in Sunset Park, Brooklyn. The Children, Caregivers, and Community (C3) Study is an outcomes-based study designed to assess the trajectories of children and families in Sunset Park along indicators such as family health and wellbeing and child development in relation to TGS program participation. The aims, scope, and protocol of the C3 Study are the subjects of this paper.
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Cuidadores , Desenvolvimento Infantil , Criança , Pré-Escolar , Humanos , Impulso (Psicologia) , Escolaridade , Emprego , Estudos Observacionais como AssuntoRESUMO
Our study examines the acceptability and feasibility of Moshi, an audio-based mobile application, among children 3-8 years old using a parent-child dyadic approach. Our 10-day within-subject pre-post study design consisted of five nights of a normal bedtime routine and a subsequent five nights exposed to one story on the Moshi application during the intervention. Each five-night period spanned three weeknights and two weekend nights. The Short-Form Children's Sleep Habits Questionnaire (SF-CSHQ) was used to measure children's sleep at baseline and post-intervention. The PROMIS, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index were used to assess parents' sleep. Among the 25 child-parent dyads, the mean child age was 4 (SD = 1.23) and 63% were male (n = 15). Mean parent age was 35 (SD = 5.83), 84% were female (n = 21), and 48.0% were Black (n = 12). For child-only comparisons, mean post-SF-CSHQ measures were lower compared to baseline. A trend in parent sleep is reported. This study shows the potential of an audio-based mobile sleep aid to improve sleep health in a racially diverse parent and child dyad sample.
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Transtornos do Sono-Vigília , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Masculino , Relações Pais-Filho , Sono , Inquéritos e QuestionáriosRESUMO
Patient health literacy is vital to clinical trial engagement. Knowledge and beliefs about clinical trials may contribute to patient literacy of clinical trials, influencing engagement, enrollment and retention. We developed and assessed a survey that measures clinical trial health knowledge and beliefs, known as the Clinical trial HEalth Knowledge and belief Scale (CHEKS). The 31 survey items in CHEKS represent knowledge and beliefs about clinical trial research (n = 409) in 2017. We examined item-scale correlations for the 31 items, eliminated items with item-scale correlations less than 0.30, and then estimated internal consistency reliability for the remaining 25 items. We used the comparative fit index (CFI) and the root mean squared error of approximation (RMSEA) to evaluate model fit. The average age of the sample was 34 (SD = 15.7) and 48% female. We identified 6 of the 31 items that had item-scale correlations (corrected for overlap) lower than 0.30. Coefficient alpha for the remaining 25 items was 0.93 A one-factor categorical confirmatory factor analytic model with 16 correlated errors was not statistically significant (chi-square = 10011.994, df = 300, p < 0.001) but fit the data well (CFI = 0.95 and RMSEA = 0.07). CHEKS can assess clinical trial knowledge and beliefs.
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Letramento em Saúde , Análise Fatorial , Feminino , Humanos , Conhecimento , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
STUDY OBJECTIVES: To assess parental experience of their child's obstructive sleep apnea (OSA) detection process and inform the development of interventions and health communication strategies to improve OSA detection. METHODS: Semistructured interviews were conducted with 30 parents of children (ages 3-14) who snored and were referred for an overnight polysomnogram (PSG). Parents (60.0% Black race, 93.3% mothers) described how their child was referred for PSG and their perceptions and feelings throughout the detection process. Parents also completed an OSA knowledge measure. Interview data were analyzed using a descriptive approach and thematic analysis was conducted using the NVivo 12 software system. RESULTS: Twenty-one themes were identified across 5 categories (first steps; PSG facilitators and barriers; health information; health care experiences; parent experiences). Respondents experienced multiple pathways to OSA detection, with more than half of referrals initiated by parental concerns (vs. screening efforts). Parents reported a willingness to take any necessary steps to help their child. Both barriers and facilitators to completing a PSG were described. Parents observed both nighttime and daytime symptoms related to OSA in their child but often did not connect the symptoms to each other until later in the process. Participants had varying degrees of OSA knowledge, with a mean knowledge score of 56% correct (range 10%-90% correct). CONCLUSIONS: Parental experiences highlight aspects of the health care system that are both effective and ineffective in detecting children with OSA. Implications include a need for strategies to promote timely detection and to provide parents with accurate information about pediatric OSA. CITATION: Honaker SM, Gopalkrishnan A, Brann M, Wiehe S, Clark AA, Chung A. "It made all the difference": a qualitative study of parental experiences ith pediatric obstructive sleep apnea detection. J Clin Sleep Med. 2022;18(8):1921-1931.
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Apneia Obstrutiva do Sono , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Mães , Pais , Polissonografia , Pesquisa Qualitativa , Apneia Obstrutiva do Sono/diagnósticoRESUMO
OBJECTIVE AND OBJECTIVE: Obstructive Sleep Apnea (OSA) is a highly prevalent disorder that disparately affects racial/ethnic minorities. OSA functional health literacy can contribute to health disparities. Documenting poor OSA functional health literacy is needed to inform research agendas, policy, and advocacy efforts. The objective of this study is to develop a scale for measuring OSA functional health literacy among diverse audiences and a variety of reading levels and to ascertain its reliability and validity. METHODS: Development of the 18-item Survey of OSA Functional Health Literacy (SOFHL) was guided by literature review and input from experts. A convenience sample of persons enrolled in a clinical trial completed the survey (n=194). The psychometric evaluation was conducted using factor analysis to identify the number of dimensions in the SOFHL and their relationship to other domains that are relevant to OSA functional health literacy. RESULTS: Internal consistency reliability (alpha) was estimated for the resulting scale and correlations with educational attainment and income completed. All respondents were Black and 29% reported average household income less than $10,000 USD. Confirmatory factor analysis provided support for two dimensions: OSA general knowledge (alpha=0.81) and self-efficacy for OSA self-management (alpha=0.71). CONCLUSIONS: Higher educational attainment and socioeconomic status were associated with better OSA functional health literacy. These results provide preliminary support for the SOFHL, a measure that can be used to assess OSA functional health literacy.
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INTRODUCTION: The American Stroke Association estimates that stroke is the fifth leading cause of death in the United States. According to the Center for Disease Control and Prevention someone in the United States has a stoke every 40 seconds, affecting more than 795,000 people of which 140,000 result in death [1]. Emerging evidence suggests that obstructive sleep apnea (OSA) is a strong risk factor for stroke. This study using The Metabolic Syndrome Outcome (MetSO) registry explored whether blacks at risk for obstructive sleep apnea (OSA) are at greater risk for a stroke. METHOD: The present study utilized data from the MetSO study, an NIH-funded cohort study of blacks with metabolic syndrome (MetS). Patients were diagnosed with MetS using standard criteria articulated in the joint interim statement for harmonizing the MetS. The study assessed OSA risk using the Apnea Risk Evaluation System (ARES); defining high risk as a total ARES score ≥6. Data was coded and analyzed by an experienced statistician using SPSS 20.0. RESULTS: A total of 1035 participants were screened for MetS in the MetSO registry. During the data collection period 875 participants were enrolled during the time of analysis. The average age of the sample was 62±14 years (range: 20-97); 71% were female, and all were of black race/ethnicity. Seventy-one percent reported finishing high school, and 43% reported annual income <10K. Descriptive analyses showed 93% of the participants were diagnosed with hypertension; 61%, diabetes; 72%, dyslipidemia; 90% were overweight/obese; 33% had a history of heart disease and 10% had a stroke history. Using the ARES screener, we estimated that 48% were at high risk for OSA. Logistic regression analysis, adjusting for age and gender, showed that patients at high risk for OSA had a nearly three-fold increase in the odds of having a stroke (OR = 2.79, 95% CI: 1.64-4.73). CONCLUSION: In the MetSO registry, a cohort of blacks with MetS, the prevalence of stroke is greater than in the general US population. Blacks at risk for OSA are particularly vulnerable to experiencing a stroke.
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Patient nonadherence to healthy lifestyle behaviors and medical treatments (like medication adherence) accounts for a significant portion of chronic disease burden. Despite the plethora of behavioral interventions to overcome key modifiable/nonmodifiable barriers and enable facilitators to adherence, short- and long-term adherence to healthy lifestyle behaviors and medical treatments is still poor. To optimize adherence, we aimed to provide a novel mobile health solution steeped in precision and personalized population health and a pantheoretical approach that increases the likelihood of adherence. We have described the stages of a pantheoretical approach utilizing tailoring, clustering/profiling, personalizing, and optimizing interventions/strategies to obtain adherence and highlight the minimal engineering needed to build such a solution.
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Adesão à Medicação , Telemedicina , Doença Crônica , Estilo de Vida Saudável , HumanosRESUMO
BACKGROUND: Participation in clinical trials among people of color remains low, compared with white subjects. This protocol describes the development of "Advancing People of Color in Clinical Trials Now!" (ACT Now!), a culturally tailored website designed to influence clinical trial decision making among people of color. OBJECTIVE: This cluster randomized study aims to test the efficacy of a culturally tailored website to increase literacy, self-efficacy, and willingness to enroll in clinical trials among people of color. METHODS: ACT Now! is a randomized trial including 2 groups: (1) intervention group (n=50) with access to the culturally tailored website and (2) control group (n=50) exposed to a standard clinical recruitment website. Clinical trial literacy and willingness to enroll in a clinical trial will be measured before and after exposure to the website corresponding to their assigned group (intervention or control). Surveys will be conducted at baseline and during the 1-month postintervention and 3-month follow-up. Website architecture and wireframing will be informed by the literature and experts in the field. Statistical analysis will be conducted using a two-tailed t test, with 80% power, at .05 alpha level, to increase clinical trial literacy, self-efficacy, and willingness to enroll in clinical trials 3 months post intervention. RESULTS: We will design a culturally tailored website that will provide leverage for community stakeholders to influence clinical trial literacy, self-efficacy, and willingness to enroll in clinical trials among racial and ethnic groups. ACT Now! applies a community-based participatory research approach through the use of a community steering committee (CSC). The CSC provides input during the research study conception, development, implementation, and enrollment. CSC relationships help foster trust among communities of color. ACT Now! has the potential to fill a gap in clinical trial enrollment among people of color through an accessible web-based website. This study was funded in July 2017 and obtained institutional review board approval in spring 2017. As of December 2019, we had enrolled 100 participants. Data analyses are expected to be completed by June 2020, and expected results are to be published in fall 2020. CONCLUSIONS: ACT Now! has the potential to fill an important gap in clinical trial enrollment among people of color through an accessible web-based website. TRIAL REGISTRATION: ClinicalTrials.gov NCT03243071; https://clinicaltrials.gov/ct2/show/NCT00102401. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17589.
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Protein tyrosine phosphorylation plays a central role in cell-signaling and is a focus of biomedical studies and cancer therapy. However, it is still challenging to identify or characterize the coordinated changes of many candidate proteins of one particular pathway or multiple pathways simultaneously. Antibody array is a recently developed approach applied for differential analysis of multiple protein posttranslational modification events in mammalian cells. It is based on the highly specific recognition between the immobilized antibodies on the array and their specific target proteins in a high-throughput screening format. Here we have described in detail two methods for differential analysis of protein tyrosine phosphorylation in cells by (1) using a single fluorescent protein capture format on membrane array and (2) a competitive protein capture method on glass surface array.
Assuntos
Anticorpos Imobilizados/farmacologia , Fosfoproteínas/análise , Fosfoproteínas/metabolismo , Análise Serial de Proteínas/métodos , Proteínas Tirosina Quinases/metabolismo , Animais , Anticorpos Fosfo-Específicos/farmacologia , Células Eucarióticas/química , Células Eucarióticas/metabolismo , Humanos , Mamíferos/metabolismo , Fosforilação , Análise Serial de Proteínas/instrumentação , Proteômica/métodosRESUMO
BACKGROUND: African American youth (aged 8-14 years) do not adhere to national dietary and physical activity guidelines. Nonadherence to these recommendations contributes to disproportionate rates of obesity compared with their white counterparts. Culturally tailored electronic health (eHealth) solutions are needed to communicate nutrition and physical activity messages that resonate with this target population. OBJECTIVE: This study aimed to identify the impact of exposure to a website hosting culturally tailored cartoons to inspire fruit and vegetable uptake and physical activity levels in African American mother-child dyads. METHODS: Statistical analysis included paired sample t tests to evaluate knowledge gains, self-efficacy, and readiness to change. Adapted items from Prochaska's Stages of Change toward the following 4 behaviors were assessed with pre- and posttest surveys: (1) fruit and vegetable selection on my plate, (2) meal preparation, (3) fruit and vegetable selection outside of home, and (4) physical activity. Open-ended comments on videos from mother-child dyads were used to determine user acceptance. Observations of repeated responses during content analysis informed coding and development of key themes. RESULTS: A final sample size of 93 mother-child dyads completed the study. Mothers reported significant improvement from precontemplation or contemplation stages to preparation or action stages for (1) fruit and vegetable selection on her plate (P=.03), (2) meal preparation for her family (P=.01), (3) fruit and vegetable selection outside the home (P<.001), and (4) physical activity (P<.001). Significant improvements were found in knowledge, stage of change, and self-efficacy for the 4 target behaviors of interest (P<.001). Children's open-ended commentary reported vicarious learning and positive character identification with brown-skinned cartoons exhibiting healthful food and exercise behaviors. Mothers commented on the lack of accessible produce in their neighborhoods not depicted in the cartoon videos. CONCLUSIONS: Culturally adapted cartoons that incorporate tailored preferences by African American families, such as race or demography, may help increase adherence to target health behaviors when developing eHealth behavior solutions.