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1.
Trials ; 22(1): 558, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419128

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgery. Factors such as cardiopulmonary bypass, aortic cross-clamping and surgical stress may precipitate renal hypoperfusion and ischaemia, inflammation and oxidative stress are associated with development of AKI. Albumin's pharmacological properties and widespread availability have the potential to mitigate these factors. However, the effect of albumin on cardiac surgery-associated AKI is unknown. OBJECTIVE: To evaluate the impact of postoperative 20% albumin infusion on kidney function after high-risk cardiac surgery. METHODS: We designed an open-label, multicentre, randomised controlled trial-the ALBICS study (ALBumin Infusion and acute kidney injury following Cardiac Surgery). A total of 590 patients undergoing high-risk cardiac surgery (combined procedure or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) will be enrolled into the study and randomly allocated to receive a postoperative 20% albumin infusion or standard care in a 1:1 ratio, stratified by centre and baseline renal function. The study fluid will be administered upon arrival in intensive care for 15 h. Patients will be followed up until 28 days after surgery or until discharge from the hospital. The primary outcome is the proportion of patients who develop AKI in both groups. Secondary outcomes to be measured are proportions of AKI stage II and III, 28-day mortality, mechanical ventilation time and length of stay in intensive care and hospital. CONCLUSION: This trial aims to determine if a postoperative infusion of concentrated albumin reduces the risk of AKI following high-risk cardiac surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619001355167. Registered on 03 October 2019-retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378383 .


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Albuminas/efeitos adversos , Austrália , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Complicações Pós-Operatórias/etiologia , Fatores de Risco
2.
Sci Rep ; 11(1): 10875, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035322

RESUMO

The SARS-CoV-2 virus is responsible for the novel coronavirus disease 2019 (COVID-19), which has spread to populations throughout the continental United States. Most state and local governments have adopted some level of "social distancing" policy, but infections have continued to spread despite these efforts. Absent a vaccine, authorities have few other tools by which to mitigate further spread of the virus. This begs the question of how effective social policy really is at reducing new infections that, left alone, could potentially overwhelm the existing hospitalization capacity of many states. We developed a mathematical model that captures correlations between some state-level "social distancing" policies and infection kinetics for all U.S. states, and use it to illustrate the link between social policy decisions, disease dynamics, and an effective reproduction number that changes over time, for case studies of Massachusetts, New Jersey, and Washington states. In general, our findings indicate that the potential for second waves of infection, which result after reopening states without an increase to immunity, can be mitigated by a return of social distancing policies as soon as possible after the waves are detected.


Assuntos
COVID-19/epidemiologia , Política de Saúde , COVID-19/patologia , COVID-19/virologia , Bases de Dados Factuais , Humanos , Massachusetts/epidemiologia , New Jersey/epidemiologia , Distanciamento Físico , Política Pública , SARS-CoV-2/isolamento & purificação , Washington/epidemiologia
3.
PLoS One ; 16(1): e0245094, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33439904

RESUMO

The transcriptional network determines a cell's internal state by regulating protein expression in response to changes in the local environment. Due to the interconnected nature of this network, information encoded in the abundance of various proteins will often propagate across chains of noisy intermediate signaling events. The data-processing inequality (DPI) leads us to expect that this intracellular game of "telephone" should degrade this type of signal, with longer chains losing successively more information to noise. However, a previous modeling effort predicted that because the steps of these signaling cascades do not truly represent independent stages of data processing, the limits of the DPI could seemingly be surpassed, and the amount of transmitted information could actually increase with chain length. What that work did not examine was whether this regime of growing information transmission was attainable by a signaling system constrained by the mechanistic details of more complex protein-binding kinetics. Here we address this knowledge gap through the lens of information theory by examining a model that explicitly accounts for the binding of each transcription factor to DNA. We analyze this model by comparing stochastic simulations of the fully nonlinear kinetics to simulations constrained by the linear response approximations that displayed a regime of growing information. Our simulations show that even when molecular binding is considered, there remains a regime wherein the transmitted information can grow with cascade length, but ends after a critical number of links determined by the kinetic parameter values. This inflection point marks where correlations decay in response to an oversaturation of binding sites, screening informative transcription factor fluctuations from further propagation down the chain where they eventually become indistinguishable from the surrounding levels of noise.


Assuntos
Regulação da Expressão Gênica , Redes Reguladoras de Genes , Modelos Biológicos , Transdução de Sinais , Animais , Humanos , Cinética
4.
Pediatr Qual Saf ; 6(1): e379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33409431

RESUMO

Sickle cell disease is a complex chronic disorder associated with increased morbidity and early mortality. The Pediatric Quality Measures Program has developed new sickle cell-specific quality measures focused on hydroxyurea (HU) counseling and annual transcranial Doppler (TCD) screening; however, these measures have not been used in a clinical setting to inform quality improvement (QI) efforts. METHODS: From 2017 to 2018, 9 sickle cell subspecialty clinics from the Pacific Sickle Cell Regional Collaborative conducted a year-long QI collaborative focused on improving the percentage of patients with HU counseling and TCD screening based on the new quality measures. After an initial kick-off meeting, the 9 sites participated in monthly conference calls. We used run charts annotated with plan-do-study-act cycle activities to track each site's monthly progress and the overall mean percentage for the entire collaborative. RESULTS: There was an overall improvement in the aggregate HU counseling from 85% to 98% (P < 0.01). For TCD screening, referral frequency changed from 85% to 90% (P = 0.76). For both measures, the variation in frequencies decreased over the year. CONCLUSION: Over 1 year, we found that a regional QI collaborative increased HU counseling. Although referral for TCD screening increased, there was no overall change in TCD completion. Overall, this QI report's findings can help clinicians adopt and implement these quality measures to improve outcomes in children.

5.
BMC Emerg Med ; 20(1): 84, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126858

RESUMO

BACKGROUND: Applied Research Associates (ARA) and the United States Army Institute of Surgical Research (USAISR) have been developing a tablet-based simulation environment for burn wound assessment and burn shock resuscitation. This application aims to supplement the current gold standard in burn care education, the Advanced Burn Life Support (ABLS) curriculum. RESULTS: Subject matter experts validate total body surface area (TBSA) identification and analysis and show that the visual fidelity of the tablet virtual patients is consistent with real life thermal injuries. We show this by noting that the error between their burn mapping and the actual patient burns was sufficiently less than that of a random sample population. Statistical analysis is used to confirm this hypothesis. In addition a full body physiology model developed for this project is detailed. Physiological results, and responses to standard care treatment, are detailed and validated. Future updates will include training modules that leverage this model. CONCLUSION: We have created an accurate, whole-body model of burn TBSA training experience in Unreal 4 on a mobile platform, provided for free to the medical community. We hope to provide learners with more a realistic experience and with rapid feedback as they practice patient assessment, intervention, and reassessment.


Assuntos
Queimaduras/terapia , Computadores de Mão , Medicina de Emergência/educação , Medicina Militar/educação , Ressuscitação/educação , Treinamento por Simulação , Superfície Corporal , Humanos , Estados Unidos
6.
Nurse Educ Today ; 85: 104229, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31738975

RESUMO

BACKGROUND: There is always a call for educational reform and further research to improve educational programs. The continuous development of new educational approaches is a work in progress. Educational strategies like team-based learning, flipped classroom, and lottery-based token economy, were used to develop a novel teaching approach. AIM: This study had two major goals. The first goal was to introduce a novel teaching approach in professional healthcare academies. The second goal was to get an in-depth understanding, from the students' perspective, about the benefits and limitations of this new teaching approach. METHOD: The study was conducted using a qualitative, phenomenological research design. Third and fourth-year nursing students completed reflective journals to describe their personal experience with the new teaching approach at the end of the semester. The students' responses were analyzed and coded using Kember's four-category coding schema for reflective writing, to extract themes using thematic analysis. FINDINGS: Seventy-five students completed and returned their reflective journals. The analysis showed various challenges and facilitators/benefits of the students' experiences. The themes that emerged from the analysis were: lack of exposure vs. a sense of achievement; lack of teamwork skills vs. role fulfillment; working with new people vs. conflict resolution; variation vs. collaboration/creativity; time management vs. constructive competition; wasting resources vs. flexibility, and proactivity/active engagement. These themes summarized why the new teaching approach worked and what barriers students faced with the new assembly. CONCLUSION: Results from the current study demonstrated the great potential of the new teaching approach. Recommendations for future research were also discussed.


Assuntos
Publicações Periódicas como Assunto , Estudantes de Enfermagem/psicologia , Ensino/normas , Currículo/normas , Currículo/tendências , Bacharelado em Enfermagem/métodos , Bacharelado em Enfermagem/normas , Avaliação Educacional/métodos , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Estudantes de Enfermagem/estatística & dados numéricos , Ensino/psicologia , Ensino/estatística & dados numéricos , Adulto Jovem
7.
PLoS One ; 14(12): e0226687, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877201

RESUMO

Large scale biological responses are inherently uncertain, in part as a consequence of noisy systems that do not respond deterministically to perturbations and measurement errors inherent to technological limitations. As a result, they are computationally difficult to model and current approaches are notoriously slow and computationally intensive (multiscale stochastic models), fail to capture the effects of noise across a system (chemical kinetic models), or fail to provide sufficient biological fidelity because of broad simplifying assumptions (stochastic differential equations). We use a new approach to modeling multiscale stationary biological processes that embraces the noise found in experimental data to provide estimates of the parameter uncertainties and the potential mis-specification of models. Our approach models the mean stationary response at each biological level given a particular expected response relationship, capturing variation around this mean using conditional Monte Carlo sampling that is statistically consistent with training data. A conditional probability distribution associated with a biological response can be reconstructed using this method for a subset of input values, which overcomes the parameter identification problem. Our approach could be applied in addition to dynamical modeling methods (see above) to predict uncertain biological responses over experimental time scales. To illustrate this point, we apply the approach to a test case in which we model the variation associated with measurements at multiple scales of organization across a reproduction-related Adverse Outcome Pathway described for teleosts.


Assuntos
Simulação por Computador , Cyprinidae/fisiologia , Modelos Biológicos , Algoritmos , Animais , Feminino , Método de Monte Carlo , Reprodução , Processos Estocásticos
8.
Glob Pediatr Health ; 6: 2333794X19847026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106244

RESUMO

National guidelines recommend that providers counsel all patients with sickle cell anemia about hydroxyurea (HU) therapy and screen children with sickle cell anemia annually for the risk of stroke with transcranial Doppler (TCD). We surveyed a national convenience sample of sickle cell disease clinicians to assess factors associated with low adherence. Adherence was 46% for TCD screening. Low adherence was associated with a lack of outcome expectancy (eg, a belief that there would be poor patient follow-up to TCD testing; P < .05). Adherence was 72% for HU counseling. Practice barriers (eg, lack of support staff or time) and a lack of agreement with HU recommendations were associated with low adherence (P < .05). This study demonstrates that different types of strategies are needed to improve TCD screening (to address follow-up and access to testing) versus HU counseling (to address physician agreement and practice barriers).

9.
BMC Syst Biol ; 12(1): 81, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30086736

RESUMO

BACKGROUND: A challenge of in vitro to in vivo extrapolation (IVIVE) is to predict the physical state of organisms exposed to chemicals in the environment from in vitro exposure assay data. Although toxicokinetic modeling approaches promise to bridge in vitro screening data with in vivo effects, they are often encumbered by a need for redesign or re-parameterization when applied to different tissues or chemicals. RESULTS: We demonstrate a parameterization of reverse toxicokinetic (rTK) models developed for the adult zebrafish (Danio rerio) based upon particle swarm optimizations (PSO) of the chemical uptake and degradation rates that predict bioconcentration factors (BCF) for a broad range of chemicals. PSO reveals a relationship between chemical uptake and decomposition parameter values that predicts chemical-specific BCF values with moderate statistical agreement to a limited yet diverse chemical dataset, and all without a need to retrain the model to new data. CONCLUSIONS: The presented model requires only the octanol-water partitioning ratio to predict BCFs to a fidelity consistent with existing QSAR models. This success begs re-evaluation of the modeling assumptions; specifically, it suggests that chemical uptake into arterial blood may be limited by transport across gill membranes (diffusion) rather than by counter-current flow between gill lamellae (convection). Therefore, more detailed molecular modeling of aquatic respiration may further improve predictive accuracy of the rTK approach.


Assuntos
Modelos Biológicos , Peixe-Zebra/metabolismo , Animais , Transporte Biológico , Toxicocinética
10.
Nat Commun ; 8: 16009, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28691706

RESUMO

Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.


Assuntos
Evolução Molecular , Modelos Genéticos , Receptor Cross-Talk , Transdução de Sinais/genética , Humanos
11.
Biophys J ; 112(8): 1539-1550, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28445746

RESUMO

Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations-an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise.


Assuntos
Redes Reguladoras de Genes , Modelos Moleculares , Algoritmos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ontologia Genética , Cadeias de Markov , Método de Monte Carlo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
BMC Syst Biol ; 11(1): 35, 2017 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-28284215

RESUMO

BACKGROUND: Physiologically-based toxicokinetic (PBTK) models are often developed to facilitate in vitro to in vivo extrapolation (IVIVE) using a top-down, compartmental approach, favoring architectural simplicity over physiological fidelity despite the lack of general guidelines relating model design to dynamical predictions. Here we explore the impact of design choice (high vs. low fidelity) on chemical distribution throughout an animal's organ system. RESULTS: We contrast transient dynamics and steady states of three previously proposed PBTK models of varying complexity in response to chemical exposure. The steady states for each model were determined analytically to predict exposure conditions from tissue measurements. Steady state whole-body concentrations differ between models, despite identical environmental conditions, which originates from varying levels of physiological fidelity captured by the models. These differences affect the relative predictive accuracy of the inverted models used in exposure reconstruction to link effects-based exposure data with whole-organism response thresholds obtained from in vitro assay measurements. CONCLUSIONS: Our results demonstrate how disregarding physiological fideltiy in favor of simpler models affects the internal dynamics and steady state estimates for chemical accumulation within tissues, which, in turn, poses significant challenges for the exposure reconstruction efforts that underlie many IVIVE methods. Developing standardized systems-level models for ecological organisms would not only ensure predictive consistency among future modeling studies, but also ensure pragmatic extrapolation of in vivo effects from in vitro data or modeling exposure-response relationships.


Assuntos
Modelos Biológicos , Toxicocinética , Animais , Cyprinidae/metabolismo , Estrogênios/farmacocinética , Estrogênios/toxicidade , Peixe-Zebra/metabolismo
13.
South Med J ; 109(2): 101-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26840965

RESUMO

OBJECTIVES: Residency interviews play an integral part in medical residency placement. We aimed to develop and evaluate a mock interview program for fourth-year medical students interested in a pediatric specialty. METHODS: A mock interview program for fourth-year medical students interested in pediatrics was developed and implemented. Preinterview quantitative data and postinterview qualitative data were collected. Fifty-nine students completed the program across three consecutive academic years. Preinterview surveys were completed regarding comfort and confidence levels specific to aspects of the interview process. Descriptive analyses were used. In addition, a focus group was held with nine of the participating students to obtain qualitative data via a paper blog process. Themes in student responses were identified through constant comparative analysis. RESULTS: Before the mock interview, students were most uncomfortable with introductory and closing remarks and their confidence levels varied by topic. A thematic analysis of focus group data identified five themes (preparation, stress reduction, interview process familiarity, confidence of skills, and receiving feedback) for which the mock interviews were most helpful. CONCLUSIONS: Implementation of a mock interview program was feasible and acceptable for senior medical students and may improve comfort and confidence levels in the residency interview process. Further longitudinal research is needed.


Assuntos
Internato e Residência/organização & administração , Entrevistas como Assunto , Pediatria/educação , Estudantes de Medicina , Grupos Focais , Humanos , Seleção de Pessoal , Adulto Jovem
14.
J Pediatr Health Care ; 29(6): 501-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25842277

RESUMO

INTRODUCTION: The aim of this study is to understand low-income parents' preferences for and barriers to receiving child health promotion information. METHODS: A mixed-methods approach was used. Data were collected in an urban pediatric primary care setting serving predominantly low-income African American families. Parents (n = 190) of 3- to 8-year-old children completed a survey; a randomly selected subset participated in focus groups. RESULTS: The quantitative and qualitative samples differed with regard to whether they would like to get parenting information from their doctors. The most commonly cited obstacles to attending parenting classes were time (50.6%), work schedule (40.6%), transportation (37.7%), and own health (22.4%). DISCUSSION: New and creative methods are needed to promote child health and development that do not increase the burden associated with raising children in the context of limited resources.


Assuntos
Negro ou Afro-Americano , Educação em Saúde/métodos , Promoção da Saúde/métodos , Pais/educação , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pediatria , Pobreza , Atenção Primária à Saúde , Criança , Pré-Escolar , Feminino , Grupos Focais , Disparidades nos Níveis de Saúde , Humanos , Masculino , Poder Familiar , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Preferência do Paciente , Relações Médico-Paciente
15.
Nat Commun ; 6: 6384, 2015 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-25812915

RESUMO

Proteasome assembly is a complex process, requiring 66 subunits distributed over several subcomplexes to associate in a coordinated fashion. Ten proteasome-specific chaperones have been identified that assist in this process. For two of these, the Pba1-Pba2 dimer, it is well established that they only bind immature core particles (CPs) in vivo. In contrast, the regulatory particle (RP) utilizes the same binding surface but only interacts with the mature CP in vivo. It is unclear how these binding events are regulated. Here, we show that Pba1-Pba2 binds tightly to the immature CP, preventing RP binding. Changes in the CP that occur on maturation significantly reduce its affinity for Pba1-Pba2, enabling the RP to displace the chaperone. Mathematical modelling indicates that this 'affinity switch' mechanism has likely evolved to improve assembly efficiency by preventing the accumulation of stable, non-productive intermediates. Our work thus provides mechanistic insights into a crucial step in proteasome biogenesis.


Assuntos
Chaperonas Moleculares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Estrutura Quaternária de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo , Eletroforese em Gel Bidimensional , Modelos Moleculares , Modelos Teóricos , Ligação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
Biophys J ; 108(4): 986-996, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25692603

RESUMO

Phosphatases play an important role in cellular signaling networks by regulating the phosphorylation state of proteins. Phosphatases are classically considered to be promiscuous, acting on tens to hundreds of different substrates. We recently demonstrated that a shared phosphatase can couple the responses of two proteins to incoming signals, even if those two substrates are from otherwise isolated areas of the network. This finding raises a potential paradox: if phosphatases are indeed highly promiscuous, how do cells insulate themselves against unwanted crosstalk? Here, we use mathematical models to explore three possible insulation mechanisms. One approach involves evolving phosphatase KM values that are large enough to prevent saturation by the phosphatase's substrates. Although this is an effective method for generating isolation, the phosphatase becomes a highly inefficient enzyme, which prevents the system from achieving switch-like responses and can result in slow response kinetics. We also explore the idea that substrate degradation can serve as an effective phosphatase. Assuming that degradation is unsaturatable, this mechanism could insulate substrates from crosstalk, but it would also preclude ultrasensitive responses and would require very high substrate turnover to achieve rapid dephosphorylation kinetics. Finally, we show that adaptor subunits, such as those found on phosphatases like PP2A, can provide effective insulation against phosphatase crosstalk, but only if their binding to substrates is uncoupled from their binding to the catalytic core. Analysis of the interaction network of PP2A's adaptor domains reveals that although its adaptors may isolate subsets of targets from one another, there is still a strong potential for phosphatase crosstalk within those subsets. Understanding how phosphatase crosstalk and the insulation mechanisms described here impact the function and evolution of signaling networks represents a major challenge for experimental and computational systems biology.


Assuntos
Modelos Biológicos , Proteína Fosfatase 2/metabolismo , Transdução de Sinais , Animais , Domínio Catalítico , Linhagem Celular , Estabilidade Enzimática , Camundongos , Proteína Fosfatase 2/química , Especificidade por Substrato
17.
Front Pediatr ; 2: 137, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25538931

RESUMO

BACKGROUND: Childhood obesity is a growing problem for children in the United States, especially for children from low-income, African American families. OBJECTIVE: The purpose of this qualitative study was to understand facilitators and barriers to engaging in healthy lifestyles faced by low-income African American children and their families. METHODS: This qualitative study used semi-structured focus group interviews with eight African American children clinically identified as overweight or obese (BMI ≥ 85) and their parents. An expert panel provided insights in developing culturally appropriate intervention strategies. RESULTS: Child and parent focus group analysis revealed 11 barriers and no definitive facilitators for healthy eating and lifestyles. Parents reported confusion regarding what constitutes nutritional eating, varying needs of family members in terms of issues with weight, and difficulty in engaging the family in appropriate and safe physical activities; to name a few themes. Community experts independently suggested that nutritional information is confusing and, often, contradictory. Additionally, they recommended simple messaging and practical interventions such as helping with shopping lists, meal planning, and identifying simple and inexpensive physical activities. CONCLUSION: Childhood obesity in the context of low-resource families is a complex problem with no simple solutions. Culturally sensitive and family informed interventions are needed to support low-income African American families in dealing with childhood obesity.

18.
Surgery ; 156(4): 861-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25239335

RESUMO

BACKGROUND: Hemorrhagic shock leads to a complex cascade of metabolic and hormonal processes that may result in hypoperfusion, end organ damage, and death even when blood pressure is restored. Studies have shown that morbidity and mortality could be attributable to a diminished availability of endothelial-derived nitric oxide (eNO). It is unclear whether adequate levels of citrulline (CIT) and arginine (ARG)--the precursors of eNO synthesis--are available to sustain the eNO needed to maintain adequate perfusion in severe shock. An indirect measure of eNO is the ratio between the levels of ARG and its inhibitor asymmetric dimethylarginine (ARG/ADMA). The purpose of the study was to identify the temporal impact of the ARG/ADMA ratio, ARG, CIT, and ADMA in response to hemorrhage and crystalloid fluid resuscitation by the use of a porcine model of severe hemorrhagic shock. METHODS: Hemorrhagic shock was induced in Yorkshire cross pigs by mimicking a bleeding pattern of rapid uncontrolled hemorrhage to achieve a shed volume of 30 mL/kg, a 50% decrease in mean arterial pressure, and an oxygen debt of >60 mL/kg. Normal saline, up to 2 times the shed blood volume, was started 1 hour after the start of hemorrhage with the goal of restoring mean arterial pressure to >50 mm Hg. Hemodynamics, blood gas measurements, and plasma samples were obtained at baseline, 1 hour after the start of hemorrhage, and 1 hour after resuscitation. Amino acids were measured by liquid chromatography coupled to mass spectrometry. RESULTS: During hemorrhage, a distinct subset of pigs was better able to tolerate ischemia than the rest. These pigs required less resuscitation, had evidence of better organ perfusion, and exhibited less of an increase in interleukin-6 (IL-6) after resuscitation. Compared with their less-tolerant counterparts, this group had a greater increase in CIT above baseline (analysis of variance, P < .05) with hemorrhage. ARG levels were similar and remained stable with hemorrhage, which indicated the similar availability of substrate for eNO synthesis but differences in the quantity produced in response to the blood volume loss. With crystalloid fluid resuscitation, ARG levels and ARG/ADMA decreased (analysis of variance, P < .05), whereas CIT remained increased in the group less able to tolerate hemorrhage. ARG/ADMA decreased proportional to greater oxygen debt during hemorrhage and greater IL-6 levels with fluid resuscitation. CONCLUSION: Our results suggest that a sufficient decrease in MAP during hemorrhagic shock is associated with a subsequent increase in IL-6, persisting impairment of end organ perfusion, and evidence of ongoing eNO deficit and an increase in ADMA despite resuscitation. The ARG/ADMA ratio reflects both of these parameters and corresponds to the increase in IL-6 and persistent ischemia after resuscitation. We propose that the mechanism of IL-6 increase in trauma derives from eNO deficiency, and the ARG/ADMA ratio more accurately depicts the pathologic mechanism responsible for increased morbidity and mortality in trauma.


Assuntos
Arginina/análogos & derivados , Arginina/sangue , Hidratação , Ressuscitação/métodos , Choque Hemorrágico/terapia , Animais , Biomarcadores/sangue , Cromatografia Líquida , Citrulina/sangue , Feminino , Interleucina-6/sangue , Masculino , Espectrometria de Massas , Choque Hemorrágico/sangue , Sus scrofa
19.
Proc Natl Acad Sci U S A ; 111(15): 5550-5, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24706803

RESUMO

Two-component signaling (TCS) serves as the dominant signaling modality in bacteria. A typical pathway includes a sensor histidine kinase (HK) that phosphorylates a response regulator (RR), modulating its activity in response to an incoming signal. Most HKs are bifunctional, acting as both kinase and phosphatase for their substrates. Unlike eukaryotic signaling networks, there is very little crosstalk between bacterial TCS pathways; indeed, adding crosstalk to a pathway can have disastrous consequences for cell fitness. It is currently unclear exactly what feature of TCS necessitates this degree of pathway isolation. In this work we used mathematical models to show that, in the case of bifunctional HKs, adding a competing substrate to a TCS pathway will always reduce response of that pathway to incoming signals. We found that the pressure to maintain cognate signaling is sufficient to explain the experimentally observed "kinetic preference" of HKs for their cognate RRs. These findings imply a barrier to the evolution of new HK-RR pairs, because crosstalk is unavoidable immediately after the duplication of an existing pathway. We characterized a set of "near-neutral" evolutionary trajectories that minimize the impact of crosstalk on the function of the parental pathway. These trajectories predicted that crosstalk interactions should be removed before new input/output functionalities evolve. Analysis of HK sequences in bacterial genomes provided evidence that the selective pressures on the HK-RR interface are different from those experienced by the input domain immediately after duplication. This work thus provides a unifying explanation for the evolution of specificity in TCS networks.


Assuntos
Bactérias/genética , Evolução Biológica , Modelos Biológicos , Receptor Cross-Talk/fisiologia , Transdução de Sinais/fisiologia , Sequência de Aminoácidos , Bactérias/metabolismo , Análise por Conglomerados , Transferência Genética Horizontal , Histidina Quinase , Dados de Sequência Molecular , Fosforilação , Filogenia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Análise de Regressão , Alinhamento de Sequência , Especificidade da Espécie
20.
J Relig Health ; 53(4): 1091-101, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23563927

RESUMO

The Black Church is the only institution that has consistently served the interest of African Americans, and there is no other institution in the African American community that rivals its influence (Camara, 2004). The spiritual well-fare, social support, health, and well-being of its people have been one of its main goals. With health disparities of African Americans still at an alarming rate, the Black Church has used informal education as a means to impart knowledge on health, as well as other non-religious and religious topics. One of the avenues least researched within the Black Church is the pastor's perception of its educational role in health and wellness and its efforts to reduce health discrimination and health disparities between African American and European Americans in the U.S. Since social justice appears as a theme and concern in the traditions of many churches, it is only appropriate that, among other things, the Black Church should address the issue of health education and interventions. The purpose of this study was to explore African American pastors' perceptions of the role of the Black Church in providing health care, health education, and wellness opportunities to African Americans. Many pastors reported their church provided some form of health education and/or health screenings. Their perceptions about the important issues facing their congregants versus African Americans in general were quite similar.


Assuntos
Negro ou Afro-Americano/psicologia , Clero/psicologia , Educação em Saúde , Promoção da Saúde , Religião e Psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estados Unidos
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