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1.
Mol Phylogenet Evol ; 179: 107664, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36403710

RESUMO

The monocot family Costaceae Nakai consists of seven genera but their mutual relationships have not been satisfactorily resolved in previous studies employing classical molecular markers. Phylogenomic analyses of 365 nuclear genes and nearly-complete plastome data provide almost fully resolved insights into their diversification. Paracostus is identified as sister to all other taxa, followed by several very short branches leading to discrete lineages, suggesting an ancient rapid radiation of these early lineages and leaving the exact relationships among them unresolved. Relationships among Chamaecostus, Dimerocostus and Monocostus confirmed earlier findings that these genera form a monophyletic group. The Afro-American Costus is also monophyletic. By contrast, Tapeinochilos appeared as a well-supported crown lineage of Cheilocostus rendering it paraphyletic. As these two genera differ morphologically from one another owing to a shift from insect- to bird-pollination, we propose to keep both names. The divergence time within Costaceae was estimated using penalized likelihood utilizing two fossils within Zingiberales, †Spirematospermum chandlerae and †Ensete oregonense, indicated a relatively recent diversification of Costaceae, between 18 and 9 Mya. Based on these data, the current pantropical distribution of the family is hypothesized to be the result of several long-distance intercontinental dispersal events, which do not correlate with global geoclimatic changes.


Assuntos
Zingiberales , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala
2.
Anesthesiology ; 130(6): 958-970, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870159

RESUMO

BACKGROUND: Cognitive decline after cardiac surgery occurs frequently and persists in a significant proportion of patients. Preclinical studies and human trials suggest that intravenous lidocaine may confer protection in the setting of neurologic injury. It was hypothesized that lidocaine administration would reduce cognitive decline after cardiac surgery compared to placebo. METHODS: After institutional review board approval, 478 patients undergoing cardiac surgery were enrolled into this multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group trial. Subjects were randomized to lidocaine 1 mg/kg bolus after the induction of anesthesia followed by a continuous infusion (48 µg · kg · min for the first hour, 24 µg · kg · min for the second hour, and 10 µg · kg · min for the next 46 h) or saline with identical volume and rate changes to preserve blinding. Cognitive function was assessed preoperatively and at 6 weeks and 1 yr postoperatively using a standard neurocognitive test battery. The primary outcome was change in cognitive function between baseline and 6 weeks postoperatively, adjusting for age, years of education, baseline cognition, race, and procedure type. RESULTS: Among the 420 allocated subjects who returned for 6-week follow-up (lidocaine: N = 211; placebo: N = 209), there was no difference in the continuous cognitive score change (adjusted mean difference [95% CI], 0.02 (-0.05, 0.08); P = 0.626). Cognitive deficit (greater than 1 SD decline in at least one cognitive domain) at 6 weeks occurred in 41% (87 of 211) in the lidocaine group versus 40% (83 of 209) in the placebo group (adjusted odds ratio [95% CI], 0.94 [0.63, 1.41]; P = 0.766). There were no differences in any quality of life outcomes between treatment groups. At the 1-yr follow-up, there continued to be no difference in cognitive score change, cognitive deficit, or quality of life. CONCLUSIONS: Intravenous lidocaine administered during and after cardiac surgery did not reduce postoperative cognitive decline at 6 weeks.


Assuntos
Anestésicos Locais/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/tendências , Lidocaína/administração & dosagem , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/etiologia , Administração Intravenosa , Idoso , Anestésicos Locais/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Lidocaína/efeitos adversos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Transtornos Neurocognitivos/induzido quimicamente , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/etiologia , Complicações Cognitivas Pós-Operatórias/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento
3.
J Plant Res ; 132(5): 589-600, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385106

RESUMO

Eriocaulon is a genus of c. 470 aquatic and wetland species of the monocot plant family Eriocaulaceae. It is widely distributed in Africa, Asia and America, with centres of species richness in the tropics. Most species of Eriocaulon grow in wetlands although some inhabit shallow rivers and streams with an apparent adaptive morphology of elongated submerged stems. In a previous molecular phylogenetic hypothesis, Eriocaulon was recovered as sister of the African endemic genus Mesanthemum. Several regional infrageneric classifications have been proposed for Eriocaulon. This study aims to critically assess the existing infrageneric classifications through phylogenetic reconstruction of infrageneric relationships, based on DNA sequence data of four chloroplast markers and one nuclear marker. There is little congruence between our molecular results and previous morphology-based infrageneric classifications. However, some similarities can be found, including Fyson's sect. Leucantherae and Zhang's sect. Apoda. Further phylogenetic studies, particularly focusing on less well sampled regions such as the Neotropics, will help provide a more global overview of the relationships in Eriocaulon and may enable suggesting the first global infrageneric classification.


Assuntos
Eriocaulaceae/classificação , Evolução Molecular , Núcleo Celular/genética , DNA de Cloroplastos/análise , Eriocaulaceae/genética , Filogenia , Análise de Sequência de DNA
4.
Hum Brain Mapp ; 39(2): 985-1003, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29164774

RESUMO

OBJECTIVES: Older adults often display postoperative cognitive decline (POCD) after surgery, yet it is unclear to what extent functional connectivity (FC) alterations may underlie these deficits. We examined for postoperative voxel-wise FC changes in response to increased working memory load demands in cardiac surgery patients and nonsurgical controls. EXPERIMENTAL DESIGN: Older cardiac surgery patients (n = 25) completed a verbal N-back working memory task during MRI scanning and cognitive testing before and 6 weeks after surgery; nonsurgical controls with cardiac disease (n = 26) underwent these assessments at identical time intervals. We measured postoperative changes in degree centrality, the number of edges attached to a brain node, and local coherence, the temporal homogeneity of regional functional correlations, using voxel-wise graph theory-based FC metrics. Group × time differences were evaluated in these FC metrics associated with increased N-back working memory load (2-back > 1-back), using a two-stage partitioned variance, mixed ANCOVA. PRINCIPAL OBSERVATIONS: Cardiac surgery patients demonstrated postoperative working memory load-related degree centrality increases in the left dorsal posterior cingulate cortex (dPCC; p < .001, cluster p-FWE < .05). The dPCC also showed a postoperative increase in working memory load-associated local coherence (p < .001, cluster p-FWE < .05). dPCC degree centrality and local coherence increases were inversely associated with global cognitive change in surgery patients (p < .01), but not in controls. CONCLUSIONS: Cardiac surgery patients showed postoperative increases in working memory load-associated degree centrality and local coherence of the dPCC that were inversely associated with postoperative global cognitive outcomes and independent of perioperative cerebrovascular damage.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Giro do Cíngulo/fisiopatologia , Memória de Curto Prazo/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem
5.
Am Heart J ; 199: 150-155, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29754654

RESUMO

OBJECTIVES: Perioperative myocardial infarction (MI) after coronary artery bypass graft surgery (CABG) has been associated with adverse outcome. Whether perioperative MI should be treated with dual antiplatelet therapy (DAPT) is unknown. We compared the effect of DAPT versus aspirin alone on short-term outcomes among patients with perioperative MI following CABG. METHODS: We used data from 3 clinical trials that enrolled patients undergoing isolated CABG: PREVENT IV (2002-2003), MEND-CABG II (2004-2005), and RED-CABG (2009-2010) (n = 9117). Perioperative MI was defined as CK-MB >5 times the upper limit of normal within 24 h of surgery (n = 2052). DAPT was defined as DAPT given after surgery and prior to discharge. A Cox regression model was used to assess the association between DAPT and 30-day nonfatal MI, stroke, or mortality after adjustment for baseline covariates. RESULTS: DAPT (n = 527) and aspirin alone (n = 1525) cohorts were similar in baseline comorbidities. Off pump bypass was used in 5.2% (n = 106) of patients. There was no difference in the 30-day composite of death, MI or stroke between patients receiving DAPT versus aspirin alone, nor in any of the individual components. There were fewer all-cause re-hospitalizations at 30 days following surgery among patients in the DAPT group (adjusted HR 0.71, CI 0.52-0.97, P = .033). CONCLUSION: One-quarter of CABG patients who had perioperative MI were treated with DAPT. DAPT was not associated with a difference in MI, stroke, or mortality at 30 days, but was associated with fewer re-hospitalizations. Further studies are needed to determine the optimal antiplatelet regimen following perioperative MI. What is already known about this subject? Perioperative myocardial infarction portends poor outcome but optimal management is currently unclear. While dual antiplatelet therapy is standard of care for acute coronary syndrome, its role in perioperative myocardial infarction is unknown. What does this study add? Dual antiplatelet therapy use during perioperative myocardial infarction was not associated with a difference in myocardial infarction, stroke or mortality at 30 days. It was, however, associated with fewer re-hospitalizations at 30 days. How might this impact on clinical practice? Dual antiplatelet therapy may be a potential treatment option for perioperative myocardial infarction after CABG surgery. Further studies are needed to better understand treatment for this disease process.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Assistência Perioperatória/métodos , Complicações Pós-Operatórias , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
6.
Anesthesiology ; 129(4): 829-851, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29621031

RESUMO

For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from "postoperative delirium" to "postoperative cognitive dysfunction or decline." Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes de Estado Mental e Demência , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/psicologia , Procedimentos Cirúrgicos Cardíacos/tendências , Disfunção Cognitiva/epidemiologia , Humanos , Testes Neuropsicológicos , Fenótipo , Complicações Pós-Operatórias/epidemiologia
7.
Anesthesiology ; 128(4): 728-744, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29389750

RESUMO

BACKGROUND: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS: Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS: The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS: In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.


Assuntos
Peptídeos beta-Amiloides , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/tendências , Disfunção Cognitiva/diagnóstico por imagem , Etilenoglicóis , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons/métodos , Idoso , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos
8.
Can J Anaesth ; 65(7): 786-796, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29644515

RESUMO

PURPOSE: The Multicenter Study of Perioperative Ischemia (McSPI) AFRisk index predicts postoperative atrial fibrillation (POAF) after cardiac surgery, but requires pre-, intra-, and postoperative data. Other more abbreviated risk indices exist, but there is no consensus on which risk index is optimal. We compared the discriminatory capacity of the McSPI AFRisk index with three indices containing only preoperative data (the CHA2DS2Vasc score, POAF score, and Kolek clinical risk prediction model), hypothesizing that the McSPI AFRisk index would have superior predictive capacity. METHODS: We retrospectively evaluated 783 patients undergoing cardiac surgery using cardiopulmonary bypass. The predictive capacity of each index was assessed by comparing receiver-operating characteristic (ROC) curves, scaled Brier scores, net reclassification indices, and the integrated discrimination indices. RESULTS: The incidence of POAF was 32.6%. The area under the curve (AUC) of the ROC curve were 0.77, 0.58, 0.66, and 0.66 for the McSPI AFRisk index, CHA2DS2Vasc score, POAF score, and Kolek clinical risk prediction model, respectively. The McSPI AFRIsk index had the highest AUC (P < 0.0001). The scaled Brier scores for the McSPI AFRisk index, CHA2DS2Vasc score, POAF score, and Kolek clinical risk prediction model were 0.23, 0.02, 0.08, and 0.07, respectively. Both net reclassification indices and integrated discrimination indices showed that the McSPI AFRisk index more appropriately identified patients at high risk of POAF. CONCLUSIONS: The McSPI AFRisk index showed superior ability to predict POAF after cardiac surgery compared with three other indices. When clinicians and investigators wish to measure the risk of POAF after cardiac surgery, they should consider using the McSPI AFRisk index.


Assuntos
Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco
10.
J Mol Cell Cardiol ; 92: 109-15, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26860460

RESUMO

Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to ß-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47×10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54×10(-5)), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Fibrilação Atrial/cirurgia , Quinase 5 de Receptor Acoplado a Proteína G/genética , Átrios do Coração/metabolismo , Fatores de Transcrição/biossíntese , Idoso , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Fibrilação Atrial/patologia , Ponte de Artéria Coronária , Feminino , Quinase 5 de Receptor Acoplado a Proteína G/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Período Pós-Operatório , Fatores de Transcrição/genética
11.
Anesth Analg ; 122(2): 539-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26797557

RESUMO

Merel Harmel, MD, was the first anesthesiologist to give anesthesia for a palliative congenital heart operation performed by Alfred Blalock, MD. He was the first resident in anesthesiology at Johns Hopkins and was the first academic department chairman at 3 different universities during his long career. He was successful because of his steadfast belief that academic anesthesia could and must flourish and his incessant optimism no matter how daunting the many obstacles in his professional life.


Assuntos
Anestesiologia/história , Anestesiologia/educação , História do Século XX , Estados Unidos
12.
Can J Anaesth ; 63(11): 1223-32, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27470233

RESUMO

PURPOSE: Postoperative cognitive dysfunction (POCD) occurs frequently after cardiac surgery. The pathophysiology of POCD remains elusive, but previous work showed that intravenous lidocaine may be protective against POCD, possibly by modulating cerebral inflammation. We hypothesized that intravenous lidocaine would attenuate the cerebral inflammatory response to cardiopulmonary bypass (CPB) by reducing the transcerebral activation gradients of platelets, leukocytes, and/or platelet-leukocyte conjugates. METHODS: We studied 202 patients undergoing cardiac surgery with CPB in this prospective randomized double-blinded placebo-controlled trial. Subjects were randomized to receive either intravenous lidocaine (bolus + 48-hr infusion) or placebo (identical infusion volume and duration). Paired jugular venous and radial arterial blood samples were drawn at several time points and analyzed by fluorescence-activated cell sorting to identify activated platelets and platelet-leukocyte conjugates. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups using repeated measures regression models with covariate adjustment for age, sex, surgery type, and CPB duration. RESULTS: Beginning after aortic cross-clamp release and peaking ten minutes after the termination of CPB, the mean (SD) transcerebral activation gradient of platelet-monocyte conjugates decreased in lidocaine-treated vs placebo-treated patients [-1.84 (11.47) mean linear fluorescence intensity (MLFI) vs 1.46 (13.88) MLFI, respectively; mean difference, -4.08 MLFI; 95% confidence interval, -7.86 to -0.29; P = 0.03). No difference was seen at any time point for activated platelets or for platelet-neutrophil conjugates. CONCLUSION: While lidocaine did not affect the systemic or transcerebral activation of platelets or leukocytes, we did observe a reduction in the transcerebral activation of platelet-monocyte conjugates after aortic cross-clamp release. This may be a manifestation of reduced cerebral inflammation during cardiopulmonary bypass in response to treatment with lidocaine. This trial was registered at ClinicalTrials.gov (NCT00938964).


Assuntos
Anestésicos Locais/uso terapêutico , Encefalopatias/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/métodos , Inflamação/tratamento farmacológico , Lidocaína/uso terapêutico , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Ponte Cardiopulmonar/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Leucócitos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Monócitos , Ativação Plaquetária , Estudos Prospectivos
13.
Kidney Int ; 88(4): 823-32, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26083657

RESUMO

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.


Assuntos
Injúria Renal Aguda/genética , Ponte de Artéria Coronária/efeitos adversos , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Biomarcadores/sangue , Creatinina/sangue , Bases de Dados Genéticas , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Fatores de Tempo
14.
Am Heart J ; 170(3): 580-90.e28, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26385043

RESUMO

BACKGROUND: Postoperative atrial fibrillation (AF) is a potentially life-threatening complication after coronary artery bypass graft (CABG) surgery. Genetic predisposition may predict risk for developing postoperative AF. METHODS: Study subjects underwent CABG surgery with cardiopulmonary bypass at Duke University Medical Center. In a discovery cohort of 877 individuals from the Perioperative Genetics and Safety Outcomes Study, we performed a genome-wide association study using a logistic regression model with a covariate adjustment for AF risk index. Single-nucleotide polymorphisms (SNPs) that met a P < 5 × 10(-5) were further tested using a replication dataset of 304 individuals from the CATHeterization GENetics biorepository, followed by meta-analysis. Potential pathways related to postoperative AF were identified through gene enrichment analysis using the top genome-wide association study SNPs (P < 10(-4)). RESULTS: Nineteen SNPs met the a priori defined discovery threshold for replication, but only 3 met nominal significance (P < .05) in the CATHeterization GENetics group, with only one-rs10504554, in the intronic region in lymphocyte antigen 96 (LY96)-showing the same direction of the effect for postoperative AF (odds ratio [OR] 0.48, 95% CI 0.34-0.68, P = 2.9 × 10(-5) vs OR 0.55, 95% CI 0.31-0.99, P = .046) and strong overall association by meta-analysis (meta-P = 4.0 × 10(-6)). Gene enrichment analysis highlighted the role of LY96 in pathways of biologic relevance to activation and modulation of innate immune responses. Our analysis also showed potential association between LY96 and nuclear factor κ-B interaction and postoperative AF through their relevance to inflammatory signaling pathways. CONCLUSIONS: In patients undergoing CABG surgery, we found genetic polymorphisms in LY96 associated with decreased risk of postoperative AF.


Assuntos
Fibrilação Atrial/genética , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Predisposição Genética para Doença , Antígeno 96 de Linfócito/genética , Polimorfismo de Nucleotídeo Único , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Doença da Artéria Coronariana/complicações , DNA/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Incidência , Antígeno 96 de Linfócito/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances
15.
Plant Cell Environ ; 38(5): 980-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25443986

RESUMO

The original report that plants emit methane (CH4 ) under aerobic conditions caused much debate and controversy. Critics questioned experimental techniques, possible mechanisms for CH4 production and the nature of estimating global emissions. Several studies have now confirmed that aerobic CH4 emissions can be detected from plant foliage but the extent of the phenomenon in plants and the precise mechanisms and precursors involved remain uncertain. In this study, we investigated the role of environmentally realistic levels of ultraviolet (UV) radiation in causing the emission of CH4 and other gases from foliage obtained from a wide variety of plant types. We related our measured emissions to the foliar content of methyl esters and lignin and to the epidermal UV absorbance of the species investigated. Our data demonstrate that the terrestrial vegetation foliage sampled did emit CH4 , with a range in emissions of 0.6-31.8 ng CH4 g(-1) leaf DW h(-1) , which compares favourably with the original reports of experimental work. In addition to CH4 emissions, our data show that carbon monoxide, ethene and propane are also emitted under UV stress but we detected no significant emissions of carbon dioxide or ethane.


Assuntos
Dióxido de Carbono/metabolismo , Monóxido de Carbono/metabolismo , Hidrocarbonetos/metabolismo , Metano/metabolismo , Folhas de Planta/efeitos da radiação , Lignina/metabolismo , Folhas de Planta/metabolismo , Raios Ultravioleta
16.
Anesth Analg ; 121(4): 861-867, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26237622

RESUMO

BACKGROUND: Hypomagnesemia has been associated with an increased risk of postoperative atrial fibrillation (POAF). Although previous studies have suggested a beneficial effect of magnesium (Mg) therapy, almost all of these are limited by small sample size and relatively low Mg dose. We hypothesized that high-dose Mg decreases the occurrence of new-onset POAF, and we tested this hypothesis by using data from a prospective trial that assessed the effect of Mg on cognitive outcomes in patients undergoing cardiac surgery. METHODS: A total of 389 patients undergoing cardiac surgery were enrolled in this double-blind, placebo-controlled trial. Subjects were randomized to receive Mg as a 50-mg/kg bolus immediately after induction of anesthesia followed by another 50 mg/kg as an infusion given over 3 hours (total dose, 100 mg/kg) or placebo. We tested the effect of Mg therapy on POAF with logistic regression, adjusting for the risk of atrial fibrillation (AF) by using the Multicenter Study of Perioperative Ischemia risk index for Atrial Fibrillation after Cardiac Surgery. RESULTS: Among the 363 patients analyzed, after we excluded patients with chronic or acute preoperative AF (placebo: n = 177; Mg: n = 186), the incidence of new-onset POAF was 42.5% (95% confidence interval [CI], 35%-50%) in the Mg group compared with 37.9% (95% CI, 31%-45%) in the placebo group (P = 0.40). The 95% CI for this absolute risk difference of 4.6% is -5.5% to 14.7%. The time to onset of POAF also was identical between the groups, and no significant effect of Mg was found in logistic regression analysis after we adjusted for AF risk (odds ratio, 1.09; 95% CI, 0.69-1.72; P = 0.73). CONCLUSIONS: High-dose intraoperative Mg therapy did not decrease the incidence of new-onset POAF after cardiac surgery.


Assuntos
Fibrilação Atrial/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cuidados Intraoperatórios/métodos , Magnésio/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos/tendências , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
17.
Can J Anaesth ; 62(6): 618-26, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25744138

RESUMO

PURPOSE: Cognitive performance after cardiac surgery can be impaired, and genetic risk factors have previously been suggested. When compared with other isoforms of the gene, the apolipoprotein epsilon 4 (APOE4) allele is associated with worse outcomes in many neurologic disorders. We hypothesized that the APOE4 allele is associated with less favourable cognitive function five years after surgery. METHODS: Caucasian patients enrolled in previously reported prospective cognitive trials in both cardiac and non-cardiac surgery participated in this retrospective cohort study. Neuropsychological function was assessed at baseline and five years postoperatively. The relationship between change in cognitive index score and APOE was evaluated using multivariable linear regression. An additive genetic model toward the epsilon 4 allele was applied with adjustment for baseline cognition, years of education, age, presence of diabetes in both cohorts, and presence of coronary artery disease in the non-cardiac surgery cohort. RESULTS: A total of 357 patients were included in this study. In the cardiac surgery group (n = 233), baseline cognitive index (P < 0.001), years of education (P = 0.04), age at time of surgery (P < 0.001), and the APOE4 allele (P = 0.009), were associated with a five-year change in cognitive index. Patients carrying the APOE4 allele showed less improvement in cognitive index scores five years after cardiac surgery compared with patients without the APOE4 allele. In the non-cardiac surgery (n = 124) group, no association was found between APOE4 allele status and change in cognitive index. CONCLUSION: We report an association between APOE4 and neurocognitive function five years following cardiac surgery. Preoperative identification of patients with the APOE4 genotype may improve stratification of cardiac surgery patients at risk for a less favourable cognitive trajectory.


Assuntos
Apolipoproteína E4/genética , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transtornos Cognitivos/etiologia , Cognição , Idoso , Alelos , Transtornos Cognitivos/genética , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
J Thromb Thrombolysis ; 38(3): 402-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24935230

RESUMO

ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels. Therefore, we tested the hypothesis that ABO blood group is associated with perioperative transfusion and subsequent survival after coronary revascularization. This retrospective study combined demographic, operative, and transfusion data, including follow-up for a median of 2,096 days, for consecutive aortocoronary bypass (CABG) and CABG/valve procedures from 1996-2009 at a tertiary referral University Heart Center. Between group differences were compared by a Kruskall Wallis test, and hazard ratios [95% confidence intervals] are reported for mortality risk-adjusted Cox proportional hazards regression analysis. From 15,454 patients, follow-up records were available for 13,627 patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed red blood cells were the most commonly transfused blood product (3 [0-5] units), while group AB received 2 [0-5] units (Kruskall Wallis Chi squared value for between group differences = 8.2; p = 0.04). Group AB favored improved long-term, postoperative survival (Hazard ratio = 0.82 [95%CI 0.68-0.98]; p = 0.03), which became evident approximately a year after surgery. In conclusion, the procoagulant phenotype of blood group AB is associated with fewer transfusions and improved late survival after cardiac surgery. Whether this finding is related to fewer perioperative transfusions, a reduction in later bleeding or other mechanisms remains speculative.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Ponte de Artéria Coronária/efeitos adversos , Transfusão de Eritrócitos , Hemorragia Pós-Operatória , Idoso , Intervalo Livre de Doença , Fator VIII/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/mortalidade , Hemorragia Pós-Operatória/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fator de von Willebrand/metabolismo
20.
J Cardiothorac Vasc Anesth ; 28(3): 462-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23972739

RESUMO

OBJECTIVE: To determine the effect of arterial normobaric hyperoxia during cardiopulmonary bypass (CPB) on postoperative neurocognitive function. The authors hypothesized that arterial hyperoxia during CPB is associated with neurocognitive decline at 6 weeks after cardiac surgery. DESIGN: Retrospective study of patients undergoing cardiac surgery with CPB. SETTING: A university hospital. PARTICIPANTS: One thousand eighteen patients undergoing coronary artery bypass graft (CABG) or CABG + valve surgery with CPB who previously had been enrolled in prospective cognitive trials. INTERVENTIONS: A battery of neurocognitive measures was administered at baseline and 6 weeks after surgery. Anesthetic and surgical care was managed as clinically indicated. MEASUREMENTS AND MAIN RESULTS: Arterial hyperoxia was assessed primarily as the area under the curve (AUC) for the duration that PaO2 exceeded 200 mmHg during CPB and secondarily as the mean PaO2 during bypass, as a PaO2 = 300 mmHg at any point and as AUC>150 mmHg. Cognitive change was assessed both as a continuous change score and a dichotomous deficit rate. Multivariate regression accounting for age, years of education, baseline cognition, date of surgery, baseline postintubation PaO2, duration of CPB, and percent change in hematocrit level from baseline to lowest level during CPB revealed no significant association between hyperoxia during CPB and postoperative neurocognitive function. CONCLUSIONS: Arterial hyperoxia during CPB was not associated with neurocognitive decline after 6 weeks in cardiac surgical patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Hiperóxia/sangue , Hiperóxia/psicologia , Complicações Pós-Operatórias/psicologia , Idoso , Feminino , Valvas Cardíacas/cirurgia , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Estudos Retrospectivos
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