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1.
Appetite ; 203: 107651, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39216823

RESUMO

Out-of-home eating (takeaway, take-out and fast-foods) is associated with intakes of higher energy and fat, and lower intakes of micronutrients, and is associated with excess weight gain. In 2017, a unique opportunity arose to measure the association between the opening of a new multi-national fast-food restaurant (McDonald's) and consumption of fast-food on young people aged 11-16. This study uses a repeated cross-sectional design to explore group level change over time with respect to out-of-home eating behaviours of young people. Two secondary schools in Redcar and Cleveland agreed to participate and facilitated the completion of a questionnaire on their pupils eating behaviours at three timepoints a) prior to the new restaurant opening, b) three months post-opening and c) nine months post opening. Reported frequency of visits to McDonald's showed a statistically significant increase in visits between 3 and 9 months of the restaurant opening. This research asks and explores the question of whether the introduction of a new multi-national fast-food restaurant influences eating habits of young people attending schools near the new outlet.

2.
Data Brief ; 52: 109984, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38152493

RESUMO

Supporting the national target of net-zero greenhouse gas emissions in the United States by 2050, the Bipartisan Infrastructure Law (BIL) authorized investments into carbon capture and storage (CCS), highlighting the need for the safe and sustainable transport of carbon dioxide (CO2). Curated to support CO2 pipeline route planning optimization and assess existing energy transport corridors, the CCS Pipeline Route Planning Database is a compilation of 47 publicly available, authoritative geospatial data resources, spanning the contiguous U.S., and some including Alaska and Hawaii. Key considerations were identified following comprehensive literature review, which included state legislation, known pipeline stressors, and energy, environmental, and social justice (EJSJ) considerations. Data layers were sorted into relevant categories (i.e., natural hazards, boundaries) and assigned preliminary weights representing potential social, environmental, and economic costs associated with routing pipelines. Version one of the CCS Pipeline Route Planning Database, made available on the Energy Data eXchange® (EDX), contains categorized vector features representing protected areas, public and energy infrastructure, EJSJ factors, potential risks, federal and state regulations and legislation, and natural features, along with associated metadata. This paper provides details on individual layers, methods used to identify data needs, acquire, and process the disparate data, as well as planned enhancements to future versions of this database.

3.
Hosp Pharm ; 58(2): 212-218, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36890959

RESUMO

Purpose: Assess the impact of electronic health record interventions on patient access to post-hospital discharge prescriptions. Methods: Five interventions were implemented in the electronic health record to improve patient access to prescriptions after discharge from hospital: electronic prior authorization, alternative medication suggestions, order sets, mail order pharmacy alerts, and medication interchange instructions. This was a retrospective cohort study of patient responses from discharges during 6 months before the first intervention implementation and 6 months after the last intervention implementation documented in the electronic health record and a transition-in-care platform. Primary endpoint was the proportion of discharges with patient-reported issues that would have been prevented by the studied interventions out of number of discharges with at least one prescription, analyzed using Chi-squared test (level of significance .05). Results: Discharges with patient-reported issues that would have been prevented by the studied interventions decreased from 1.68 to 1.07 out of 1000 discharges with prescriptions (P < .001). Conclusion: Interventions in the electronic health record reduced barriers faced by patients to picking up prescriptions post-discharge from hospital, potentially leading to improved patient satisfaction and improved health outcomes. Important factors to consider for electronic health record intervention implementation are workflow development and intrusiveness of clinical decision support. Multiple targeted electronic health record interventions can improve patients' access to prescriptions after discharge from hospital.

4.
Front Big Data ; 6: 1227189, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38169611

RESUMO

Subsurface interpretations and models rely on knowledge from subject matter experts who utilize unstructured information from images, maps, cross sections, and other products to provide context to measured data (e. g., cores, well logs, seismic surveys). To enhance such knowledge discovery, we advanced the National Energy Technology Laboratory's (NETL) Subsurface Trend Analysis (STA) workflow with an artificial intelligence (AI) deep learning approach for image embedding. NETL's STA method offers a validated science-based approach of combining geologic systems knowledge, statistical modeling, and datasets to improve predictions of subsurface properties. The STA image embedding tool quickly extracts images from unstructured knowledge products like publications, maps, websites, and presentations; categorically labels the images; and creates a repository for geologic domain postulation. Via a case study on geographic and subsurface literature of the Gulf of Mexico (GOM), results show the STA image embedding tool extracts images and correctly labels them with ~90 to ~95% accuracy.

5.
Food Sci Nutr ; 10(11): 3689-3723, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36348796

RESUMO

Obesity remains a serious public health concern in rich countries and the current obesogenic food environments and food insecurity are predictors of this disease. The impact of these variables on rising obesity trends is, however, mixed and inconsistent, due to measurement issues and cross-sectional study designs. To further the work in this area, this review aimed to summarize quantitative and qualitative data on the relationship between these variables, among adults and children across high-income countries. A mixed-method systematic review was conducted using 13 electronic databases, up to August 2021. Two authors independently extracted data and evaluated quality of publications. Random-effects meta-analysis was used to estimate the odds ratio (OR) for the association between food insecurity and obesity. Where statistical pooling for extracted statistics related to food environments was not possible due to heterogeneity, a narrative synthesis was performed. Meta-analysis of 36,113 adults and children showed statistically significant associations between food insecurity and obesity (OR: 1.503, 95% confidence interval: 1.432-1.577, p < .05). Narrative synthesis showed association between different types of food environments and obesity. Findings from qualitative studies regarding a reliance on energy-dense, nutrient-poor foods owing to their affordability and accessibility aligned with findings from quantitative studies. Results from both qualitative and quantitative studies regarding the potential links between increased body weight and participation in food assistance programs such as food banks were supportive of weight gain. To address obesity among individuals experiencing food insecurity, wide-reaching approaches are required, especially among those surrounded by unhealthy food environments which could potentially influence food choice.

6.
Nutr Bull ; 47(2): 199-207, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36045094

RESUMO

Healthy plant-based diets (hPBD) are being promoted to reduce the risks of cardiovascular and associated diseases. This study investigates short-term adherence to a hPBD to examine whether these dietary changes impact weight and cardiovascular risk factors. A simple, uncontrolled, before and after design was used. Twenty women (mean BMI 31 ± 4 kg/m2 ) participated in a 6-week hPBD intervention. Participants completed a 3-week reset, eliminating all refined sugar, heavily processed foods, artificial sweeteners, alcohol, meat, fish, dairy and oil from their diets, which could then be reintroduced into their diet if the participant chose to do so. Participants had 1-h, weekly group support sessions. A weight loss of 4.4 kg, SD = 1.8 kg (n = 17, t = 10.2, p < 0.001) was observed after 6 weeks following the hPBD. BMI reduced from 31 to 29 kg/m2 (mean reduction = 1.38, SD = 0.76, n = 17, t = 7.49, p < 0.001). Reductions for waist circumference (mean reduction = 4.4 cm, SD = 5.22 cm, n = 8, t = 2.55, p = 0.034), LDL cholesterol (mean reduction = 0.600 mmol/L, SD = 0.828, n = 17, t = 2.81, p = 0.014) and total cholesterol (mean = 0.525 mmol/L, SD = 0.969, n = 17, t = 2.24, p = 0.040) were also observed. Body fat % was not significantly reduced (mean reduction = 2.3, SD = 6.6, n = 17, t = 1.49, p = 0.154). Dietary data were obtained from 17 participants at week 3 and from six participants at week 6. Energy intake at week 3 decreased compared with baseline (mean reduction = 1068 kcal/day, SD = 585 kcal, n = 17, t = 7.07, p < 0.001) and at week 6 (mean reduction = 715 kcal, SD = 645 kcal, n = 6, t = 2.72, p = 0.042). Protein, saturated fat and cholesterol intakes were also lower at weeks 3 and 6 compared with baseline. Fibre intake increased significantly from baseline to week 6 (mean increase = 11.3 g/day, SD = 8.9, n = 6, t = 3.11, p = 0.027) whilst sugar intake decreased from baseline to week 3 (mean reduction = 26.0 g/day, SD = 22.3, n = 17, t = 4.52, p < 0.001), but the reduction at week 6 was not significant. These results suggest that motivated participants can learn to adopt new dietary patterns for a few weeks at least with some support. This study demonstrated positive effects of a hPBD on weight reduction, cholesterol and BMI over a short time period, although the short- and long-term adherence to this diet requires further research.


Assuntos
Gorduras na Dieta , Ingestão de Energia , Colesterol , Dieta Vegetariana , Ingestão de Alimentos , Feminino , Humanos , Açúcares , Redução de Peso
7.
Data Brief ; 40: 107761, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35005150

RESUMO

The Carbon Ore Resources Database (CORD) is a working collection of 399 data files associated with carbon ore resources in the United States. The collection includes spatial/non-spatial, filtered, processed, and secondary data files with original data acquisition efforts focused on domestic coal resources. All data were acquired via open-source, online sources from a combination of 18 national, state, and university entities. Datasets are categorized to represent aspects of carbon ore resources, to include: Geochemistry, Geology, Infrastructure, and Samples. Geospatial datasets are summarized and analyzed by record and dataset density or the number of records or datasets per 400 square kilometer grid cells. Additionally, the "CORD Platform," an ArcGIS Online geospatial dashboard web application, enables users to interact and query with CORD datasets. The CORD provides a single database and location for data-driven analytical needs associated with the utilization of carbon ore resources.

8.
Nutr Bull ; 46(2): 160-171, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34149313

RESUMO

The nutritional requirements of adolescence and the reported poor UK eating behaviours of young people are a significant public health concern. Schools are recognised as an effective 'place' setting to enable improvement to nutrition outcomes. The COVID-19 pandemic resulted in UK school closures from March 2020. In re-opening in September 2020, schools were required to meet guidelines to ensure the minimised impact of COVID-19 on the population (DfE 2020). We aimed to evaluate the impact of COVID-19 school guidelines on secondary and post-16 (16-18 years) food provision. An online survey was posted on 8th October to 1st December 2020, targeted at young people, parents and staff of secondary/post-16 education establishments in the UK. Two hundred and fifty-two responses were received, of which 91% reported a change in their school food provision, 77% reported time for lunch was shortened and 44% indicated the provision was perceived as less healthy during September 2020 (post-lockdown school return) compared with March 2020 (pre-lockdown). Analyses demonstrated that time, limited choice and healthiness impacted negatively upon young people's school food experience. The COVID-19 pandemic has presented a huge challenge to the delivery of healthy school food to young people. Therefore, schools require more support in following national food standards and incorporating nutrition education and behaviour change strategies within current guidelines.

9.
Obes Rev ; 22(5): e13186, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33442954

RESUMO

Understanding the social and environmental influencers of eating behaviours has the potential to improve health outcomes for young people. This review aims to explore the effectiveness of school nutrition interventions and the perceptions of young people experiencing a nutrition focused intervention or change in school food policy. A comprehensive systematic search identified studies published between 1 December 2007 to 20 February 2020. Twenty-seven studies were included: 22 quantitative studies of nutrition related outcomes and five qualitative studies reporting views and perceptions of young people (combined sample of 22,138 participants, mean ages 12-18 years). The primary outcome was nutrition knowledge/dietary behaviours, with secondary outcomes exploring body mass index (BMI) and wellbeing. Due to the heterogeneity of studies, a narrative results description is presented. The findings demonstrate that school nutrition programmes can be effective in reducing sugar, sugar sweetened beverages (SSB) and saturated fat and increasing fruit and vegetable (FV) intake. The lived experiences of young people in a school context provide valuable insights that should be considered in the development of effective school food policy and interventions. This review affirms the significant role that schools can play in supporting good nutrition in all young people and provides opportunities to inform the school food agenda.


Assuntos
Comportamento Alimentar , Instituições Acadêmicas , Adolescente , Criança , Dieta , Humanos , Política Nutricional , Verduras
10.
Toxicol Sci ; 170(2): 499-508, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31093666

RESUMO

Most idiosyncratic drug-induced liver injury appears to result from an adaptive immune attack on the liver. Recent evidence suggests that the T-cell response may be facilitated by the loss of immune tolerance. In this study, we explored the hypothesis that constitutively released hepatocyte-derived exosomes (HDE) are important for maintaining normal liver immune tolerance. Exosomes were isolated from the conditioned medium of primary human hepatocytes via polymer precipitation. Mock controls were prepared by processing fresh medium that was not hepatocyte exposed with precipitation reagent. THP-1 monocytes were then treated with HDE or an equivalent volume of mock control for 24 h, followed by a 6-h stimulation with LPS. HDE exposure resulted in a significant decrease in the LPS-induced media levels of interleukin-1ß and interleukin-8. Gene expression profiling performed in THP-1 cells just prior to LPS-induced stimulation identified a significant decrease among genes associated with innate immune response. MicroRNA (miRNA) profiling was performed on the HDE to identify exosome contents that may drive immune suppression. Many of the predicted mRNA target genes for the most abundant microRNAs in HDE were among the differentially expressed genes in THP-1 cells. Taken together, our data suggest that HDE play a role in maintaining normal liver immune tolerance. Future experiments will explore the possibility that drugs causing idiosyncratic liver injury promote the loss of homeostatic HDE signaling.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Exossomos/fisiologia , Hepatócitos/citologia , Tolerância Imunológica , Fígado/imunologia , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Humanos , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Transcriptoma
11.
J Pharm Sci ; 105(2): 950-964, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26869439

RESUMO

Immune-mediated drug-induced hepatotoxicity is often unrecognized as a potential mode of action due to the lack of appropriate in vitro models. We have established an in vitro rat donor-matched hepatocyte and Kupffer cell co-culture (HKCC) model to study immune-related responses to drug exposure. Optimal cell culture conditions were identified for the maintenance of co-cultures based on cell longevity, monolayer integrity, and cytokine response after lipopolysaccharide (LPS) exposure. Hepatocyte monocultures and HKCCs were then used to test a subset of compounds associated with hepatotoxic effects with or without LPS. Cytokine levels and metabolic activity (cytochrome P450 3A [Cyp3A]) were measured after a 48-h exposure to monitor endotoxin-induced changes in acute phase and functional end points. LPS-activated HKCCs, but not hepatocyte monocultures, treated with trovafloxacin or acetaminophen, compounds associated with immune-mediated hepatotoxicity, showed LPS-dependent decreases in interleukin-6 production with concomitant increases in Cyp3A activity. Differential endotoxin- and model-dependent alterations were observed in cytokine profiles and Cyp3A activity levels that corresponded to specific compounds. These results indicate the utility of the HKCC model system to discern compound-specific effects that may lead to enhanced or mitigate hepatocellular injury due to innate or adaptive immune responses.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatócitos/metabolismo , Mediadores da Inflamação/metabolismo , Células de Kupffer/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Glucocorticoides/toxicidade , Hepatócitos/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Células de Kupffer/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
12.
Toxicol Appl Pharmacol ; 277(2): 131-7, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24699182

RESUMO

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.


Assuntos
Alanina Transaminase/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ensaios Enzimáticos Clínicos , Antagonistas de Receptores de GABA-A/toxicidade , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sulfonas/toxicidade , Testes de Toxicidade/métodos , meta-Aminobenzoatos/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Biomarcadores/sangue , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/genética , Cães , Feminino , Marcadores Genéticos , Glutamato Desidrogenase/sangue , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , L-Iditol 2-Desidrogenase/sangue , Fígado/enzimologia , Fígado/patologia , Masculino , MicroRNAs/sangue , Necrose , Valor Preditivo dos Testes , Ratos , Ratos Sprague-Dawley , Medição de Risco , Especificidade da Espécie , Fatores de Tempo
13.
J Biochem Mol Toxicol ; 27(10): 471-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23918466

RESUMO

We have recently shown that primary rat hepatocytes organized in micropatterned cocultures with murine embryonic fibroblasts (HepatoPac™) maintain high levels of liver functions for at least 4 weeks. In this study, rat HepatoPac was assessed for its utility to study chemical bioactivation and associated hepatocellular toxicity. Treatment of HepatoPac cultures with acetaminophen (APAP) over a range of concentrations (0-15 mM) was initiated at 1, 2, 3, or 4 weeks followed by the assessment of morphological and functional endpoints. Consistent and reproducible concentration-dependent effects on hepatocyte structure, viability, and basic functions were observed over the 4-week period, and were exacerbated by depleting glutathione using buthionine sulfoximine or inducing CYP3A using dexamethasone, presumably due to increased reactive metabolite-induced stress and adduct formation. In conclusion, the results from this study demonstrate that rat HepatoPac represents a structurally and functionally stable hepatic model system to assess the long-term effects of bioactivated compounds.


Assuntos
Acetaminofen/toxicidade , Trifosfato de Adenosina/antagonistas & inibidores , Analgésicos não Narcóticos/toxicidade , Glutationa/antagonistas & inibidores , Hepatócitos/efeitos dos fármacos , Trifosfato de Adenosina/biossíntese , Albuminas/metabolismo , Animais , Butionina Sulfoximina/farmacologia , Técnicas de Cocultura , Citocromo P-450 CYP3A/metabolismo , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Glutationa/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Masculino , Modelos Biológicos , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos , Ureia/metabolismo
14.
Rev. para. med ; 27(1)jan.-mar. 2013. ilus
Artigo em Português | LILACS-Express | LILACS | ID: lil-676562

RESUMO

Objetivo: relatar um caso de síndrome de transfusão feto-fetal (STFF), demonstrando a importância do correto eprecoce diagnóstico ultrassonográfico e quando necessário a indicação da fotocoagulação a laser fetoscópica(FCLF) como melhor conduta terapêutica. Relato do caso: mulher 18 anos, secundigesta, gestação gemelarmonocoriônica diamniótica com diagnóstico ultrassonográfico tardio de STFF, devido não realização de prénatal.Realizados dois procedimentos de amniodrenagem como medida paliativa, evoluindo para partoprematuro no oitavo dia de internação. Um dos gêmeos evoluiu a óbito na UTI neonatal. Considerações finais:percebe-se a necessidade de uma melhor assistência pré-natal, treinamento dos profissionais médicos para arealização do diagnóstico ultrassonográfico correto e de investimentos em centros de Medicina fetal no Parápara tratamento adequado


Objective: to report a case of twin-twin transfusion syndrome (TTTS), demonstrating the importance of correctand early ultrasound diagnosis and when necessary the indication of laser photocoagulation fetoscópica (FCLF)as the best therapeutic approach. Case report: 18 years woman, in her second, diamniótica monochorionic twinpregnancy with late diagnosis of TTTS, because failure to carry out prenatal care. Evolved into premature laborafter cesarean with indication of two procedures amniodrenagem. After a cesarean section withoutcomplications was death of the twins in the NICU. Final considerations: we perceive the need to support theadequacy of prenatal care, training of medical professionals to perform the correct ultrasound diagnosis andinvestments in fetal medicine centers in Pará.

15.
J Biochem Mol Toxicol ; 27(3): 204-12, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23315828

RESUMO

Primary hepatocytes display functional and structural instability in standard monoculture systems. We have previously developed a model in which primary hepatocytes are organized in domains of empirically optimized dimensions and surrounded by murine embryonic fibroblasts (HepatoPac™). Here, we assess the long-term phenotype of freshly isolated and cryopreserved rat hepatocytes in a 96-well HepatoPac format. The viability, cell polarity (actin microfilaments, bile canaliculi), and functions (albumin, urea, Phase I/II enzymes, transporters) of fresh and cryopreserved rat hepatocytes were retained in HepatoPac at similar levels for at least 4 weeks as opposed to rapidly declining over 5 days in collagen/Matrigel™ sandwich cultures. Pulse or continuous exposure of rat HepatoPac to GW-7647, a selective agonist of PPARα, caused reproducible induction of CYP4A1 and 3-hydroxy-3-methylglutaryl-CoA synthase over 4 weeks. In conclusion, rat HepatoPac in a 96-well format can be used for chronic dosing of highly functional hepatocytes and assessment of perturbed hepatocellular pathways.


Assuntos
Técnicas de Cocultura/métodos , Fibroblastos/citologia , Hepatócitos/citologia , Fígado/citologia , Citoesqueleto de Actina/metabolismo , Animais , Polaridade Celular/genética , Criopreservação , Hepatócitos/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas , Camundongos , Ratos
16.
Am J Forensic Med Pathol ; 31(1): 1-3, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19949318

RESUMO

The majority of cardiac related deaths are due to ischemic heart disease, with the most common clinical scenario being severe coronary artery atherosclerosis resulting in left ventricular myocardial infarction. However, infarction of other cardiac chambers does occur, and often has specific clinical associations. We report a case of a 70-year-old man who suffered from left atrial infarction that resulted in a transmural rupture of his left atrium. The patient had a history of rheumatic heart disease, mitral valve stenosis, and severe atherosclerotic coronary artery disease. Four days before death, he underwent mitral valve replacement and left circumflex coronary artery bypass. Two days later, he developed atrial fibrillation. On the day of death, he had decreased mental status, questionable seizure activity, hematemesis, ventricular tachycardia, and eventually asystole. At autopsy, he had significant hemopericardium with a fibrinous pericarditis and bilateral hemothoraces (total blood volume: 1250 mL). A 0.1 to 0.2 cm left atrial transmural defect was identified. The prosthetic mitral valve was free of vegetations, and completely intact. Similarly, the left circumflex artery bypass graft was completely patent and unremarkable. Severe calcific atherosclerosis was of his native left circumflex and left main coronary arteries. Microscopic examination revealed acute myocardial infarction of the left atrium at the rupture site. The anatomy of atrial circulation as well as the pathology and consequences of atrial infarction are discussed.


Assuntos
Átrios do Coração/patologia , Ruptura Cardíaca Pós-Infarto/patologia , Complicações Pós-Operatórias , Idoso , Ponte de Artéria Coronária , Doença da Artéria Coronariana/patologia , Patologia Legal , Implante de Prótese de Valva Cardíaca , Hematemese/etiologia , Hemotórax/patologia , Humanos , Masculino , Valva Mitral/cirurgia , Derrame Pericárdico/patologia , Pericardite/patologia , Convulsões/etiologia
17.
Drug Metab Lett ; 3(1): 28-34, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19356114

RESUMO

GyrATPase is a cellular enzyme that has been used as an antibacterial target for treatment of nosocomial and community acquired bacterial infections. The leading chemical series targeted at inhibiting this enzyme, indazoles, were rapidly cleared in rats (CL > 70 mL/min/kg). The predominant metabolite identified in both urine and bile samples from a bile duct-cannulated study corresponded to direct glucuronidation of the parent compound and was excreted rapidly. Subsequently, a carefully designed analog was used to pinpoint the site of glucuronidation (N-glucuronidation) by incubation with rat hepatocytes and followed by mass spectrometry analysis. Reaction mapping with an array of recombinant UGT isozymes revealed that N-glucuronidation was predominantly catalyzed by the UGT1A family of enzymes. Based on the results, the following approaches were considered to reduce or eliminate glucuronidation: 1) adding sterically hindered substitutions on the phenyl ring of the indazole core; 2) changing the electron distribution by substituting with electron-donating or -withdrawing groups; 3) replacing the site of glucuronidation. The resulted compounds were evaluated in vitro in rat hepatocytes to assess their metabolic stabilities followed by in vivo efficacy studies in the murine peritonitis sepsis model (at 50 mg/kg) for selected compounds.


Assuntos
Azetidinas/química , Azetidinas/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/metabolismo , Indazóis/química , Indazóis/farmacologia , Animais , Bactérias/metabolismo , Ductos Biliares/fisiologia , Glucuronídeos/metabolismo , Hepatócitos/metabolismo , Indazóis/metabolismo , Masculino , Peritonite/microbiologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sepse/metabolismo , Sepse/microbiologia , Relação Estrutura-Atividade
18.
Anal Biochem ; 385(2): 321-5, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19032927

RESUMO

Bacterial resistance to antibiotic therapy remains a worldwide problem. In Pseudomonasaeruginosa, rates of efflux confer inherent resistance to many antimicrobial agents, including fluoroquinolones, due to a high level of expression and a relatively high turnover number of the efflux pumps in gram-negative bacteria. To understand the roles of efflux pumps in both the influx and efflux of compounds in P. aeruginosa and to aid the chemistry compound design by bridging in vitro enzymatic binding data (IC(50) values) with whole cell results (MIC numbers), a collaborative effort was put forward to validate a series of bacterial penetration/accumulation assays for assessment of intracellular drug concentration. Initially, using 2-(4-dimethylaminostyryl)-1-ethylpyridinium cation (DMP) as the tracer, a 96-well fluorescence assay was established to measure the time-dependent accumulation of DMP in wild-type (PAO1), MexABOprM deletion (PAO200), and MexABOprM-MexCDOprJ-MexJKL:FRT deletion mutants (PAO314). At steady state, the order of DMP accumulation was PAO314>PAO200>PAO1. Subsequently, the established assay conditions were applied to a radiolabeled assay format using (3)H-labeled ciprofloxacin. At the concentration tested, the accumulation of [(3)H]ciprofloxacin approached a plateau after 15 min and the amount of accumulation in PAO314 was higher (~2- to 10-fold) than that in PAO1. Finally, with an additional step of cell lysis, a liquid chromatography/mass spectrometry-based assay was established with ciprofloxacin with (i) superior sensitivity (the detection limit can be as low as 0.24 ng/ml for ciprofloxacin) and (ii) the ability to monitor cold or nonfluorescent compounds in a drug discovery setting.


Assuntos
Ciprofloxacina/metabolismo , Pseudomonas aeruginosa/metabolismo , Espectrometria de Massas em Tandem/métodos , Transporte Biológico , Cromatografia Líquida , Ciprofloxacina/análise , Fluorescência , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/metabolismo , Compostos de Piridínio
19.
Phys Rev Lett ; 101(21): 218702, 2008 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-19113460

RESUMO

Random Boolean networks are models of disordered causal systems that can occur in cells and the biosphere. These are open thermodynamic systems exhibiting a flow of energy that is dissipated at a finite rate. Life does work to acquire more energy, then uses the available energy it has gained to perform more work. It is plausible that natural selection has optimized many biological systems for power efficiency: useful power generated per unit fuel. In this Letter, we begin to investigate these questions for random Boolean networks using Landauer's erasure principle, which defines a minimum entropy cost for bit erasure. We show that critical Boolean networks maximize available power efficiency, which requires that the system have a finite displacement from equilibrium. Our initial results may extend to more realistic models for cells and ecosystems.


Assuntos
Modelos Estatísticos , Modelos Teóricos , Software , Processos Estocásticos
20.
J Contin Educ Health Prof ; 27(2): 111-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17576630

RESUMO

INTRODUCTION: Few studies have rigorously evaluated the effectiveness of health-related continuing education using satellite distribution. This study assessed participants' professional characteristics and their changes in knowledge, attitudes, and actions taken after viewing a public health preparedness training course on mass vaccination broadcast nationally by satellite. METHODS: A three-part survey design was used to evaluate training effectiveness. Paper-based questionnaires were distributed at a stratified sample of downlink facilities to collect knowledge and attitude responses before and after the broadcast. Six weeks later, willing participants were invited by e-mail to complete a Web-based follow-up questionnaire to assess actions taken as a result of viewing the broadcast. Paired t-tests and McNemar's chi-square were used to compare changes in attitude from before to after the broadcast, after the broadcast to follow-up, and before the broadcast to follow-up. RESULTS: A total of 544 paper-based questionnaires were received from 59 of 70 sampled sites. The pre- and post assessments administered the day of the broadcast demonstrated statistically significant knowledge gain (p < .001) and an increased belief immediately following the broadcast that mass vaccination clinics are important to their organizations' public health activities (p < .001). Of the 291 respondents who completed the follow-up online questionnaire, 44% (n = 128) reported they implemented or planned some form of action after the broadcast. Reported actions were higher among public health workers most likely to be directly involved in preparedness and immunization activities. DISCUSSION: This evaluation assessed (1) participants' professional characteristics, (2) knowledge gain, (3) self-reported actions taken following the broadcast, (4) program satisfaction, and (5) suggested improvements for future satellite broadcast programs. The study's methodology of using a Web-based survey for follow-up is a relatively economical tool for assessing longer-term continuing education program objectives.


Assuntos
Educação Continuada/métodos , Internet , Enfermagem em Saúde Pública , Astronave , Telecomunicações , Coleta de Dados , Planejamento em Desastres , Educação a Distância , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estados Unidos
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