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1.
J Surg Res ; 292: 182-189, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37633247

RESUMO

INTRODUCTION: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). MATERIALS AND METHODS: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. RESULTS: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). CONCLUSIONS: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.

2.
Proc Natl Acad Sci U S A ; 117(2): 1119-1128, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31888983

RESUMO

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.


Assuntos
Imunoterapia/métodos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/uso terapêutico , Injeções Intralesionais , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Linfócitos B , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linfócitos T CD8-Positivos/imunologia , Humanos , Imunidade Celular , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana , Interleucina-10 , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Repressoras/genética , Estações do Ano , Pele , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Esqualeno/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Vacinação
3.
Immunity ; 38(6): 1271-84, 2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23791644

RESUMO

Naive CD4⁺ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, we generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hr of in vitro polarization toward T helper 1 (Th1) and T helper 2 (Th2) cell lineages. Our analysis indicated that even at this very early time point, cell-specific gene regulation and enhancers were at work directing lineage commitment. Further examination of lineage-specific enhancers identified transcription factors (TFs) with known and unknown T cell roles as putative drivers of lineage-specific gene expression. Lastly, an integrative analysis of immunopathogenic-associated SNPs suggests a role for distal regulatory elements in disease etiology.


Assuntos
Cromatina/metabolismo , Histonas/metabolismo , Doenças do Sistema Imunitário/imunologia , Células Th1/imunologia , Células Th2/imunologia , Diferenciação Celular/genética , Linhagem da Célula/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Histonas/genética , Humanos , Doenças do Sistema Imunitário/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Equilíbrio Th1-Th2
4.
Catheter Cardiovasc Interv ; 99(4): 1243-1250, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34851550

RESUMO

OBJECTIVE: The purpose of this study is to assess the utility of ambulatory cardiac monitoring (ACM) in detecting delayed advanced conduction abnormalities (DACA) and associated 30-day mortality. BACKGROUND: DACA are well-known complications of TAVR and may be associated with post-discharge mortality within 30-days. METHODS: Between October 2019 and October 2020, TAVR patients who were discharged home without a permanent pacemaker (PPM) were monitored with an ACM device for 14-days. The incidence of DACA at follow up, mortality and readmission within 30-days were investigated. The risk of DACA was assessed in three patient categories based on a composite of their 12-lead electrocardiogram (ECG) data. Group I: Normal pre-TAVR, periprocedural, and discharge ECGs. Group II: Normal pre-TAVR and abnormal subsequent ECGs. Group III. Abnormal baseline and abnormal subsequent ECGs. RESULTS: Among 340 TAVR patients, 248 were discharged home with an ACM device. The overall incidence of DACA was 7% (n = 17), of whom 4% (n = 10) required a PPM. Mortality and readmission between discharge and 30 days was 0% and 8.3%, respectively. Stratification of patients identified 96 (38.7%) patients in Group I: 50 (20%) in Group II, and 102 (41%) in Group III. The incidence of DACA requiring a PPM was 0% in Group I, 4% (n = 2) in Group II, and 8.5% (n = 8) in Group III (p < 0.004). CONCLUSIONS: In TAVR patients who were discharged home with ACM, none died between discharge and 30-days. For those with normal baseline, perioperative and discharge ECG, there were no events of DACA at 14-days.


Assuntos
Estenose da Valva Aórtica , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter , Assistência ao Convalescente , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Arritmias Cardíacas/etiologia , Estimulação Cardíaca Artificial/efeitos adversos , Eletrocardiografia/efeitos adversos , Humanos , Marca-Passo Artificial/efeitos adversos , Alta do Paciente , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
5.
J Card Surg ; 37(1): 117-123, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34791705

RESUMO

BACKGROUND: Minimally invasive heart valve surgery has previously been shown to be safe and feasible in obese patients. Within this population, we investigated the effect of obesity class on the patient outcomes of minimally invasive aortic valve replacement (mini-AVR). METHODS: A single-center retrospective cohort study of consecutive patients with obese body mass indices (BMIs) who underwent mini-AVR between 2012 and 2020. Patients were stratified into three groups according to Centers for Disease Control and Prevention adult obesity classifications: Class I (BMI: 30.0-<35.0), Class II (BMI: 35.0-<40.0), and Class III (BMI ≥ 40.0). The primary outcomes were postoperative length of stay (LOS), 30-day mortality, and direct cost. RESULTS: Among 206 obese patients who underwent mini-AVR, LOS (Class I 5 [3-7] vs. Class II 6 [5-7] vs. Class III 6 [5-7] days; p = .056), postoperative 30-day mortality (Class I 2.44% [n = 3] vs. Class II 4.44% [n = 2] vs. Class III 7.89% [n = 3]; p = .200), and costs (Class I $24,118 [$20,237-$29.591] vs. Class II $22,215 [$18,492-$28,975] vs. Class III $24,810 [$20,245-$32,942] USD; p = .683) did not differ between obesity class cohorts. CONCLUSIONS: Mini-AVR is safe and feasible to perform for obese patients regardless of their obesity class. Patients with obesity should be afforded the option of minimally invasive aortic valve surgery regardless of their obesity class.


Assuntos
Valva Aórtica , Implante de Prótese de Valva Cardíaca , Adulto , Valva Aórtica/cirurgia , Índice de Massa Corporal , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Obesidade/complicações , Estudos Retrospectivos , Esternotomia , Resultado do Tratamento
6.
Chin J Traumatol ; 25(6): 336-344, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35337713

RESUMO

PURPOSE: Olecranon fractures are particularly vulnerable to distraction and subsequent fracture dislocation due to the high tensile forces. Surgical treatment aims at reducing the fracture and restoring the anatomical joint surface condition, as well as neutralizing the strain inhibiting fracture healing. The XS nail® (Intercus GmbH, Bad Blankenberg, Germany), an intramedullary implant exerting compression across the entire fracture surface, unlike plates, leaves a minimal extra-cortical profile, and can be secured with threaded locking wires, thereby retaining the anatomical reduction without displacement or steps within the articular surface, which was often found in tension band wiring. After encouraging initial results, the long-term outcome was assessed. METHODS: This retrospective study evaluated the long-term outcome of patients surgically treated at our trauma center between January 2002 and December 2005 using the XS nail®. Patients over the age of 18 years eligible for the study must have undergone surgery for isolated, recent (less than 14 days) traumatic olecranon fractures, without concomitant injuries to the ipsilateral elbow and forearm. Further exclusion criteria were pseudarthrosis, re-fractures and osteotomy for distal humerus surgery, as well as polytraumatized patients unable to aid in their own recovery. Data were retrospectively gathered by standardised questionnaire and patient records, as well as surgery and anesthesiology reports. Data analysis was performed using Microsoft Office Excel® 2016. RESULTS: There were 32 patients, 13 males (mean age 49.0 years) and 19 females (mean age 68.9 years) with 11 Schatzkers type D, 7 each type A and C, 5 type B and 2 type E at an average of 55.2 months, all showing complete consolidation. Of them, 6 patients had a loss of range of motion with more than 10° in the sagittal plane, and only 1 patient exceeded 10° reduction of supination. Twenty-five patients reported being pain-free under all circumstances, and all but 2 patients (93.75%) had returned to their previous activity level. The average disabilities of the arm, shoulder and hand score was 21.15 (range 0-88.3), and the overall Mayo elbow performance index was 91.87, without complications, such as wound infection, neurovascular impairment or premature hardware removal. CONCLUSION: Using the XS nail® system, all fracture types can be successfully treated and the rate of complications was lower than that treated by standard methods published in current literature. An excellent functional outcome, high range of motion as well as good retention of reduction without soft tissue irritation makes this a very suitable implant for fractures subject to tension.


Assuntos
Lesões no Cotovelo , Fraturas Ósseas , Olécrano , Fraturas da Ulna , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Olécrano/cirurgia , Olécrano/lesões , Estudos Retrospectivos , Fraturas da Ulna/cirurgia , Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Amplitude de Movimento Articular , Resultado do Tratamento
7.
Anesth Analg ; 132(3): 770-776, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32815872

RESUMO

BACKGROUND: Perioperative pulse oximetry hemoglobin saturation (Spo2) measurement is associated with fewer desaturation and hypoxia episodes. However, the sigmoidal nature of oxygen-hemoglobin dissociation limits the accuracy of estimation of the partial pressure of oxygen (Pao2) >80 mm Hg and correspondingly limits the ability to identify when Pao2 >80 mm Hg but falling. We hypothesized that a proxy measurement for oxygen saturation (Oxygen Reserve Index [ORI]) derived from multiwavelength pulse oximetry may allow additional warning time before critical desaturation or hypoxia. To test our hypothesis, we used a Masimo multiwavelength pulse oximeter to compare ORI and Spo2 warning times during apnea in high-risk surgical patients undergoing cardiac surgery. METHODS: This institutional review board-approved prospective study (NCT03021473) enrolled American Society of Anesthesiologists physical status III or IV patients scheduled for elective surgery with planned preinduction arterial catheter placement. In addition to standard monitors, an ORI sensor was placed and patients were monitored with a pulse oximeter displaying the ORI, a nondimensional parameter that ranges from 0 to 1. Patients were then preoxygenated until ORI plateaued. Following induction of anesthesia, mask ventilation with 100% oxygen was performed until neuromuscular blockade was established. Endotracheal intubation was accomplished using videolaryngoscopy to confirm placement. The endotracheal tube was not connected to the breathing circuit, and patients were allowed to be apneic. Ventilation was resumed when Spo2 reached 94%. We defined ORI warning time as the time from when the ORI alarm registered (based on the absolute value and the rate of change) until the Spo2 decreased to 94%. We defined the Spo2 warning time as the time for Spo2 to decrease from 97% to 94%. The added warning time provided by ORI was defined as the difference between ORI warning time and Spo2 warning time. RESULTS: Forty subjects were enrolled. Complete data for analysis were available from 37 patients. The ORI alarm registered before Spo2 decreasing to 97% in all patients. Median (interquartile range [IQR]) ORI warning time was 80.4 seconds (59.7-105.9 seconds). Median (IQR) Spo2 warning time was 29.0 seconds (20.5-41.0 seconds). The added warning time provided by ORI was 48.4 seconds (95% confidence interval [CI], 40.4-62.0 seconds; P < .0001). CONCLUSIONS: In adult high-risk surgical patients, ORI provided clinically relevant added warning time of impending desaturation compared to Spo2. This additional time may allow modification of airway management, earlier calls for help, or assistance from other providers. The potential patient safety impact of such monitoring requires further study.


Assuntos
Apneia/diagnóstico , Procedimentos Cirúrgicos Cardíacos , Alarmes Clínicos , Hipóxia/diagnóstico , Monitorização Intraoperatória , Oximetria , Oxiemoglobinas/metabolismo , Idoso , Apneia/sangue , Apneia/etiologia , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Diagnóstico Precoce , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Respiração Artificial
8.
J Card Surg ; 36(7): 2400-2406, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33821496

RESUMO

BACKGROUND: Octogenarians undergoing cardiac surgery have higher mortality than their younger counterparts. OBJECTIVES: To determine if various risk factors have the same effect on mortality in octogenarians as in younger patients. METHODS: The National Inpatient Sample data set from 2004 to 2014 was queried to select patients aged 65 years and older who underwent either coronary artery bypass grafting (CABG), valvular heart surgery (VHS), or both (CABG + VHS) within 10 days of hospital admission. The patients were divided into two groups 65-79 years and 80 years and greater. Hospital mortality, patient demographics, comorbidities, and type of hospital admission was evaluated and compared using χ2 and multivariable logistic regressions. RESULTS: About 397,713 patients were identified including 86,345 (21.7%) aged 80 and above. Octogenarians had higher in-hospital mortality for all procedures: CABG (4.94% vs. 2.39%, p < .001), VHS (5.49% vs. 4.08%, p < .001), and CABG + VHS (7.59% vs. 5.95%, p < .001), and this relationship persisted when gender, race, comorbidities, and type of hospital admission were controlled for: CABG (odds ratio [OR] = 1.71; 95% confidence interval [CI] 1.62-1.81); VHS (OR = 1.18; 95% CI 1.11-1.27); and CABH + VHS (OR = 1.17; 95%CI 1.10-1.26). Female gender, renal, or heart failure, nonelective admission, and CABG + VHS were associated with increased risk of in-hospital mortality. Octogenarians had higher rates of these factors (p < .001). The effect size of renal and heart failure and type of surgery was smaller for octogenarians. CONCLUSIONS: Octogenarians undergoing cardiac surgery have higher rates of nonelective admissions, renal and heart failure, and female gender, which are most strongly associated with in-hospital mortality. Differing effect sizes suggest that certain risk factors, such as renal and heart failure, contribute more to mortality in younger patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
Clin Transplant ; 34(3): e13787, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31961010

RESUMO

BACKGROUND: This study aims to investigate the association between social behaviors of increased-risk donors (IRD) and recipient outcomes after heart transplantation. METHODS: The United Network for Organ Sharing (UNOS) database was queried to identify patients who received a heart transplant between 2004 and 2015. Patients were grouped based on donor's risk status (IRD vs standard risk donor [SRD]). Recipients of IRD were categorized based on donor social behaviors (SB), and recipient survival was assessed. Cox regression analysis was used to identify associations between SB of donors and recipient survival. RESULTS: Out of 22 333 heart transplantations performed during the study period, 2769 (12%) received an IRD graft with the following SB: Unprofessional tattoos or piercings (n = 1722) (63%), cocaine use (n = 916) (33%), heavy smoking (n = 437) (16%), and heavy alcohol abuse (n = 610) (22%). Viral screens detected 72(3%) hepatitis B virus (HBV) positive and 12 (0.4%) hepatitis C virus (HCV) positive at donation. There was no difference in recipient survival based on both donor risk and their social behaviors. Cox regression analysis found only donor HCV infection and non-identical ABO mismatch to be associated with poor recipient survival among recipients of IR grafts. CONCLUSION: Cardiac allografts from IRD, serologically negative for viruses, can safely be used. There is no association between social behaviors of IRD and recipient survival.


Assuntos
Transplante de Coração , Hepatite C , Sobrevivência de Enxerto , Humanos , Comportamento Social , Doadores de Tecidos , Resultado do Tratamento
10.
J Card Surg ; 35(3): 706-709, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981433

RESUMO

Significant aortic calcification is a known sequelae of homograft aortic root replacement and creates a treatment challenge if these patients require cardiac reintervention. The standard surgical option for patients requiring an aortic valve replacement in the setting of a calcified aortic homograft has been a Bentall procedure, which is high-risk with extended cross-clamp, cardiopulmonary bypass and operative times. We present a patient with a severely calcified aortic homograft who underwent successful valve replacement using a rapid deployment aortic valve leaving the aortic root and arch intact and avoiding the more extensive redo aortic root replacement. Similar cases in the literature are rare.


Assuntos
Aorta/patologia , Valva Aórtica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Falha de Prótese , Aloenxertos , Implante de Prótese Vascular/métodos , Calcinose , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Índice de Gravidade de Doença
11.
J Card Surg ; 34(12): 1573-1576, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31714642

RESUMO

PURPOSE: Cardiothoracic surgeons are frequently called upon to perform surgical pericardial drainage procedures (pericardial window) for pericardial effusions. These procedures have therapeutic value, but the diagnostic value of such procedures is debated. We set out to determine the sensitivity of pericardial drainage to detect the disease when cytology, microbiology, and pathology are evaluated. METHODS: A retrospective chart review of patients who underwent pericardial windows from 1 July 2011 to 1 January 2018 at a single academic institution was conducted. All patients who had undergone a recent trauma or cardiac procedure were excluded. Cytology, microbiology, and pathology were examined. The charts were then carefully reviewed to determine if a clinical diagnosis was reached. Sensitivity was then calculated for all diseases and for those that should have been able to be detected. RESULTS: One hundred sixty-two patients who had undergone a pericardial drainage procedure were identified; 49 patients were excluded for recent cardiac procedure or trauma. Of the 113 patients who met our inclusion criteria, 56 patients (49.6%) were female with a mean age of 59.7 ± 15.1 years. A diagnosis based on the pathology, microbiology, or cytology was obtained for 27 patients. The most common pathologies detected were adenocarcinoma (11), bacteremia (9), and small cell lung cancer (3); 56 patients had underlying pathologies that would have been possible to detect with either pathology, microbiology, or cytology. The most common detectable diagnoses were adenocarcinoma (20), bacteremia (12), and lymphoma (7). The most common undetectable diagnoses were idiopathic (17), cardiorenal fluid overload (17), and viral (11). The sensitivity of a pericardial drainage procedure for detecting disease was 0.24 for all cases, and 0.48 when restricted to cases where a detectable disease was present. CONCLUSION: Cytology, microbiology, and pathology for pericardial drainage procedures were unable to detect a diagnosis for 76% of all cases and greater than 50% of cases with the theoretically detectable disease. Pericardial drainage procedures have a clear therapeutic value, but they have limited diagnostic utility.


Assuntos
Derrame Pericárdico/etiologia , Derrame Pericárdico/cirurgia , Técnicas de Janela Pericárdica , Adulto , Idoso , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
Plant Biotechnol J ; 16(10): 1756-1766, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29509991

RESUMO

Arabica coffee (Coffea arabica) has a small gene pool limiting genetic improvement. Selection for caffeine content within this gene pool would be assisted by identification of the genes controlling this important trait. Sequencing of DNA bulks from 18 genotypes with extreme high- or low-caffeine content from a population of 232 genotypes was used to identify linked polymorphisms. To obtain a reference genome, a whole genome assembly of arabica coffee (variety K7) was achieved by sequencing using short read (Illumina) and long-read (PacBio) technology. Assembly was performed using a range of assembly tools resulting in 76 409 scaffolds with a scaffold N50 of 54 544 bp and a total scaffold length of 1448 Mb. Validation of the genome assembly using different tools showed high completeness of the genome. More than 99% of transcriptome sequences mapped to the C. arabica draft genome, and 89% of BUSCOs were present. The assembled genome annotated using AUGUSTUS yielded 99 829 gene models. Using the draft arabica genome as reference in mapping and variant calling allowed the detection of 1444 nonsynonymous single nucleotide polymorphisms (SNPs) associated with caffeine content. Based on Kyoto Encyclopaedia of Genes and Genomes pathway-based analysis, 65 caffeine-associated SNPs were discovered, among which 11 SNPs were associated with genes encoding enzymes involved in the conversion of substrates, which participate in the caffeine biosynthesis pathways. This analysis demonstrated the complex genetic control of this key trait in coffee.


Assuntos
Cafeína/metabolismo , Coffea/genética , Genoma de Planta , Coffea/metabolismo , Polimorfismo de Nucleotídeo Único
13.
Nature ; 488(7409): 116-20, 2012 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-22763441

RESUMO

The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 10(9) bases of the mouse genome possess a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences, but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.


Assuntos
Regulação da Expressão Gênica/genética , Genoma/genética , Camundongos/genética , Mapeamento Físico do Cromossomo , Sequências Reguladoras de Ácido Nucleico/genética , Acetilação , Animais , Cromatina/metabolismo , Imunoprecipitação da Cromatina , Sequência Conservada , Elementos Facilitadores Genéticos/genética , Evolução Molecular , Masculino , Metilação , Camundongos Endogâmicos C57BL , Anotação de Sequência Molecular , Motivos de Nucleotídeos , Especificidade de Órgãos , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Fatores de Transcrição/metabolismo
14.
Thorac Cardiovasc Surg ; 66(3): 255-260, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-26906971

RESUMO

BACKGROUND: Debate over revascularization of asymptomatic carotid stenosis before cardiac surgery is ongoing. In this study, we analyze cardiac surgery outcomes in patients with asymptomatic carotid stenosis at a single hospital. METHODS: In this study, 1,781 patients underwent cardiac surgery from January 2012 to June 2013; 1,357 with preoperative screening carotid duplex were included. Patient demographics, comorbidities, degree of stenosis, postoperative complications, and mortality were evaluated. Chi-square test and logistic regression analysis were performed. RESULTS: Asymptomatic stenosis was found in 403/1,357 patients (29.7%; 355 moderate and 48 severe). Patients with stenosis, compared with those without, were older (71.7 ± 11 vs. 66.3 ± 12 years; p < 0.01). Females were more likely to have stenosis (odd ratio, = 1.7; 95% confidence interval, 1.4-2.2); however, patients were predominantly male in both groups. There were no significant differences in the rates of mortality and postoperative complications, including stroke and transient ischemic attack (TIA). Postoperative TIA occurred in 3/1,357(0.2%); only one had moderate stenosis. Inhospital stroke occurred in 21/1,357 (1.5%) patients; stroke rates were 2.3% (8/355) with moderate stenosis and 2.1% (1/48) severe stenosis. There were 59/1,357 (4.3%) deaths; patients with stenosis had a mortality rate of 4.2% (17/403); however, no postoperative stroke lead to death. Multivariable logistic regression analysis with adjustment for age, gender, race, comorbidities, and postoperative complications did not show an impact of carotid stenosis on postoperative mortality and development of stroke after cardiac surgery. CONCLUSION: This study suggests that patients with asymptomatic carotid stenosis undergoing cardiac surgery are not at increased risk of postoperative complications and mortality; thus, prophylactic carotid revascularization may not be indicated.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Estenose das Carótidas/complicações , Cardiopatias/cirurgia , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Distribuição de Qui-Quadrado , Feminino , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Cardiopatias/mortalidade , Humanos , Ataque Isquêmico Transitório/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla
15.
Stem Cells ; 34(11): 2648-2660, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27334848

RESUMO

Understanding the regulation of cell-cell interactions during the formation of compact myocardial structures is important for achieving true cardiac regeneration through enhancing the integration of stem cell-derived cardiomyocytes into the recipient myocardium. In this study, we found that cellular repressor of E1A-stimulated genes 1 (CREG1) is highly expressed in both embryonic and adult hearts. Gain- and loss-of-function analyses demonstrated that CREG1 is required for differentiation of mouse embryonic stem (ES) cell into cardiomyocytes and the formation of cohesive myocardium-like structures in a cell-autonomous fashion. Furthermore, CREG1 directly interacts with Sec8 of the exocyst complex, which tethers vesicles to the plasma membrane. Site-directed mutagenesis and rescue of CREG1 knockout ES cells showed that CREG1 binding to Sec8 is required for cardiomyocyte differentiation and cohesion. Mechanistically, CREG1, Sec8, and N-cadherin colocalize at intercalated discs in vivo and are enriched at cell-cell junctions in cultured cardiomyocytes. CREG1 overexpression enhances the assembly of adherens and gap junctions. By contrast, its knockout inhibits the Sec8-N-cadherin interaction and induces their degradation. These results suggest that the CREG1 binding to Sec8 enhances the assembly of intercellular junctions and promotes cardiomyogenesis. Stem Cells 2016;34:2648-2660.


Assuntos
Proteínas de Transporte/genética , Coração/crescimento & desenvolvimento , Células-Tronco Embrionárias Murinas/metabolismo , Miócitos Cardíacos/metabolismo , Organogênese/genética , Proteínas Repressoras/genética , Animais , Animais Recém-Nascidos , Caderinas/genética , Caderinas/metabolismo , Proteínas de Transporte/metabolismo , Adesão Celular , Comunicação Celular , Diferenciação Celular , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Junções Comunicantes/metabolismo , Junções Comunicantes/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento , Teste de Complementação Genética , Proteínas de Membrana , Camundongos , Camundongos Knockout , Células-Tronco Embrionárias Murinas/citologia , Mutagênese Sítio-Dirigida , Miócitos Cardíacos/citologia , Cultura Primária de Células , Proteínas Repressoras/deficiência , Transdução de Sinais
16.
J Immunol ; 195(5): 2452-60, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26232429

RESUMO

LPS-induced TLR4 activation alters cellular bioenergetics and triggers proteolytic cleavage of AMPKα and HIF-1α expression in leukocytes. In human leukocytes, and more specifically neutrophils, AMPKα cleavage yields 55- and 35-kDa protein fragments. In this study, we address the mechanism by which AMPKα is cleaved and its relevance to human health. Our data indicate that AMPKα cleavage is linked to MMP9 expression and that both are required for mammalian target of rapamycin complex-1 and S6K1 activation and HIF-1α expression in LPS-stimulated human and mice leukocytes. Three key observations support this conclusion. First, no changes in AMPKα and TLR4 signaling intermediates (mammalian target of rapamycin complex-1/S6 kinase 1/HIF-1α) were detected in LPS-stimulated MMP9-deficient mice leukocytes. Second, rMMP9 cleaved human AMPKα ex vivo, producing degradation products similar in size to those detected following LPS stimulation. Third, MMP9 inhibitors prevented AMPKα degradation and HIF-1α expression in LPS-activated human leukocytes, whereas AMPK activators blocked MMP9 and HIF-1α expression. Significantly, AMPKα degradation, MMP9, and TLR4 signaling intermediates were all detected in leukocytes from patients with type 2 diabetes mellitus and patients following cardiopulmonary bypass surgery. Plasma from these two patient cohorts induced AMPKα cleavage and TLR4 signaling intermediates in healthy donor leukocytes and either a TLR4 inhibitor or polymyxin prevented these outcomes. Detection of AMPKα degradation, MMP9 expression, and TLR4 signaling intermediates described in this study in leukocytes, the most readily available human cells for clinical investigation, may provide a powerful tool for further exploring the role of TLR4 signaling in human diseases and lead to identification of new, context-specific therapeutic modalities for precision medicine.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leucócitos/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Complexos Multiproteicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptor 4 Toll-Like/metabolismo , Idoso , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Immunoblotting , Leucócitos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
J Card Surg ; 32(12): 830-832, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29098719

RESUMO

Congenital aortico-left ventricular tunnel requires surgical repair during childhood. Long-term surveillance is essential in these patients given the risk for aortic aneurysm development in adulthood. We describe an aortic root replacement for an aortic aneurysm five decades following the closure of an aortic-left ventricular tunnel.


Assuntos
Aorta/anormalidades , Aneurisma Aórtico/cirurgia , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Complicações Pós-Operatórias/cirurgia , Enxerto Vascular/métodos , Aorta/cirurgia , Aneurisma Aórtico/etiologia , Feminino , Ventrículos do Coração/cirurgia , Humanos , Pessoa de Meia-Idade
18.
Cardiology ; 133(3): 191-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26613584

RESUMO

Coronary subclavian steal syndrome is a rare but important condition that occurs after a left internal mammary artery (LIMA) to coronary artery bypass in the setting of a stenotic left subclavian artery. The lack of blood flow through the subclavian artery causes the reversal of flow in the LIMA so that it essentially steals blood from the myocardium. In order to avoid this complication, many surgeons now opt to either revascularize the stenotic subclavian artery prior to coronary artery bypass grafting or to use an alternate vessel as the bypass graft. Here, we present the case of an asymptomatic patient with poor exercise tolerance who was recently diagnosed with both triple-vessel coronary disease and peripheral arterial disease, which was most notably characterized by occlusion of the left subclavian artery. This case demonstrates the surgical management of this complex clinical entity.


Assuntos
Ponte de Artéria Coronária/métodos , Síndrome do Roubo Coronário-Subclávio/cirurgia , Intervenção Coronária Percutânea , Angiografia , Síndrome do Roubo Coronário-Subclávio/diagnóstico , Exercício Físico , Humanos , Masculino , Pessoa de Meia-Idade
20.
Perfusion ; 31(2): 131-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26034193

RESUMO

Femoral cannulation during cardiopulmonary bypass has become a common approach for many cardiac procedures and serves as an important access option, especially during minimally invasive cardiac surgery. Opponents, however, argue that there is significant risk, including site-specific and overall morbidity, which makes the use of this modality dangerous compared to conventional aortoatrial cannulation techniques. We analyzed our institutional experience to elucidate the safety and efficacy of femoral cannulation. All data were collected from a single hospital's cardiac surgery database. A total of 346 cardiac surgeries were evaluated from September 2012 to September 2013, of which 85/346 (24.6%) utilized a minimally invasive approach. Of the 346 operations performed, 72/346 (20.8%) utilized femoral cannulation while 274/346 (79.2%) used aortoatrial cannulation. Stroke occurred in 1/72 (1.39%) after femoral cannulation, specifically, in a conventional sternotomy patient, while it occurred in 6/274 (2.19%) [p=0.67] after aortoatrial cannulation. When comparing postoperative complications between the femoral cannulation and aortoatrial cannulation groups, the rates of atrial fibrillation [10/72 (13.9%) versus 46/274 (16.8%), p=0.55], renal failure [2/72 (2.78%) versus 11/274 (4.01%), p=0.62], prolonged ventilation time [4/72 (5.56%) versus 27/274 (9.85%), p=0.26] and re-operation for bleeding [3/72 (4.17%) versus 13/274 (4.74%), p=0.84] showed no significant difference. Selective femoral cannulation provides a safe alternative to aortoatrial cannulation for cardiopulmonary bypass and is especially important when performing minimally invasive cardiac surgery. When comparing aortoatrial and femoral cannulation, we found no significant difference in the postoperative complication rates and overall mortality.


Assuntos
Cateterismo Cardíaco/métodos , Ponte Cardiopulmonar/métodos , Bases de Dados Factuais , Artéria Femoral , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Retrospectivos , Dispositivos de Acesso Vascular
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