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Artigo em Inglês | MEDLINE | ID: mdl-32462550


PURPOSE: The prospective, multicenter SMART SF trial demonstrated the acute safety and effectiveness of the 56-hole porous tip irrigated contact force (CF) catheter for drug-refractory paroxysmal atrial fibrillation (PAF) ablation with a low primary adverse event rate (2.5%), leading to FDA approval of the catheter. Here, we are reporting the long-term effectiveness and safety results that have not yet been reported. METHODS: Ablations were performed using the 56-hole porous tip irrigated CF catheter guided by the 3D mapping system stability module. The primary effectiveness endpoint was freedom from atrial tachyarrhythmia (including atrial fibrillation, atrial tachycardia, and/or atrial flutter), based on electrocardiographic data at 12 months. Atrial tachyarrhythmia recurrence occurring 3 months post procedure, acute procedural failures such as lack of entrance block confirmation of all PVs, and undergoing repeat procedure for atrial fibrillation in the evaluation period (91 to 365 days post the initial ablation procedure) were considered to be effectiveness failures. RESULTS: Seventy-eight patients (age 64.8 ± 9.7 years; male 52.6%; Caucasian 96.2%) participated in the 12-month effectiveness evaluation. Mean follow-up time was 373.5 ± 45.4 days. The Kaplan-Meier estimate of freedom from 12-month atrial tachyarrhythmia was 74.9%. Two procedure-related pericardial effusion events were reported at 92 and 180 days post procedure. There were no pulmonary vein stenosis complications or deaths reported through the 12-month follow-up period. CONCLUSIONS: The SMART SF 12-month follow-up evaluation corroborates the early safety and effectiveness success previously reported for PAF ablation with STSF.

Glycobiology ; 28(11): 832-840, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169672


Post-translational modification of proteins namely glycosylation influences cellular behavior, structural properties and interactions including during ovarian follicle development and atresia. However, little is known about protein glycosylation changes occurring in diabetes mellitus in ovarian tissues despite the well-known influence of diabetes on the outcome of successful embryo implantation. In our study, the use of PGC chromatography-ESI mass spectrometry in negative ion mode enabled the identification of 138 N-glycans and 6 O-glycans on the proteins of Streptozotocin-induced (STZ) diabetic mouse ovarian tissues (n = 3). Diabetic mouse ovaries exhibited a relative decrease in sialylation, fucosylation and, to a lesser extent, branched N-linked glycan structures, as well as an increase in oligomannose structures on their proteins, compared with nondiabetic mouse ovaries. Changes in N-glycans occurred in the diabetic liver tissue but were more evident in diabetic ovarian tissue of the same mouse, suggesting an organ-specific effect of diabetes mellitus on protein glycosylation. Although at a very low amount, O-GalNAc glycans of mice ovaries were present as core type 1 and core type 2 glycans; with a relative increase in the NeuGc:NeuAc ratio as the most significant difference between control and diabetic ovarian tissues. STZ-treated mice also showed a trend towards an increase in TNF-α and IL1-B inflammatory cytokines, which have previously been shown to influence protein glycosylation.

Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Hiperglicemia/induzido quimicamente , Ovário/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Feminino , Glicosilação , Hiperglicemia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina
Sci Rep ; 8(1): 2114, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29391475


Diabetes has been linked with impaired fertility but the underlying mechanisms are not well defined. Here we use a streptozotocin-induced diabetes mouse model to investigate the cellular and biochemical changes in conceptus and maternal tissues that accompany hyperglycaemia. We report that streptozotocin treatment before conception induces profound intra-cellular protein ß-O-glycosylation (O-GlcNAc) in the oviduct and uterine epithelium, prominent in early pregnancy. Diabetic mice have impaired blastocyst development and reduced embryo implantation rates, and delayed mid-gestation growth and development. Peri-conception changes are accompanied by increased expression of pro-inflammatory cytokine Trail, and a trend towards increased Il1a, Tnf and Ifng in the uterus, and changes in local T-cell dynamics that skew the adaptive immune response to pregnancy, resulting in 60% fewer anti-inflammatory regulatory T-cells within the uterus-draining lymph nodes. Activation of the heat shock chaperones, a mechanism for stress deflection, was evident in the reproductive tract. Additionally, we show that the embryo exhibits elevated hyper-O-GlcNAcylation of both cytoplasmic and nuclear proteins, associated with activation of DNA damage (É£H2AX) pathways. These results advance understanding of the impact of peri-conception diabetes, and provide a foundation for designing interventions to support healthy conception without propagation of disease legacy to offspring.

Diabetes Mellitus Experimental/complicações , Embrião de Mamíferos/patologia , Fertilização , Retardo do Crescimento Fetal/etiologia , Complicações na Gravidez/etiologia , Gravidez em Diabéticas/fisiopatologia , Útero/patologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Embrião de Mamíferos/imunologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Feminino , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Glicosilação , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Reprodução , Útero/imunologia , Útero/metabolismo
Mol Reprod Dev ; 83(8): 701-13, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27409576


The preimplantation embryo is extraordinarily sensitive to environmental signals and events such that perturbations can alter embryo metabolism and program an altered developmental trajectory, ultimately affecting the phenotype of the adult individual; indeed, the physical environment associated with in vitro embryo culture can attenuate development. Defining the underlying metabolic changes and mechanisms, however, has been limited by the imaging technology used to evaluate metabolites and structural features in the embryo. Here, we assessed the impact of in vitro fertilization and culture on mouse embryos using three metabolic markers: peroxyfluor 1 (a reporter of hydrogen peroxide), monochlorobimane (a reporter of glutathione), and Mitotracker Deep Red (a marker of mitochondria). We also evaluated the distribution pattern of histone 2AX gamma (γH2AX) in the nuclei of 2- and 8-cell embryos and blastocysts to investigate the degree of DNA damage caused by in vitro embryo culture. In vitro-fertilized embryos, in vivo-developed embryos, and in vivo-fertilized embryos recovered and cultured in vitro were compared at the 2-, 8-cell, and blastocyst stages. In addition to assessments based on fluorescence intensity, textural analysis using Gray Level Co-occurrence Matrix (GLCM), a statistical approach that assesses texture within an image, was used to evaluate peroxyfluor 1, monochlorobimane, and Mitotracker Deep Red staining in an effort to develop a robust metric of embryo quality. Our data provide strong evidence of modified metabolic parameters identifiable as altered fluorescence texture in embryos developed in vitro. Thus, texture-analysis approach may provide a means of gaining additional insight into embryo programming beyond conventional measurements of staining intensity for metabolic markers. Mol. Reprod. Dev. 83: 701-713, 2016 © 2016 Wiley Periodicals, Inc.

Blastocisto/citologia , Blastocisto/metabolismo , Núcleo Celular/metabolismo , Animais , Feminino , Fertilização In Vitro , Masculino , Camundongos
J Physiol ; 594(5): 1451-63, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26456386


Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes.

Endotélio Vascular/patologia , Hipóxia Fetal/complicações , Cloreto de Sódio na Dieta/efeitos adversos , Doenças Vasculares/etiologia , Rigidez Vascular , Animais , Endotélio Vascular/fisiopatologia , Feminino , Masculino , Artérias Mesentéricas/patologia , Artérias Mesentéricas/fisiopatologia , Camundongos , Gravidez
BMC Complement Altern Med ; 14: 7, 2014 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-24400734


BACKGROUND: As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify socio-demographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients. METHODS: We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center. RESULTS: Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p < 0.001), and previous radiation therapy (p = 0.004) were significantly associated with WTP. Travel difficulty (p = 0.002), concern with experimentation (p = 0.013), and lack of interest in acupuncture (p < 0.001) were significant barriers to WTP. Barriers differed significantly by socio-demographic factors with white people more likely to endorse travel difficulty (p = 0.018) and non-white people more likely to report concern with experimentation (p = 0.024). Older patients and those with lower education were more likely to report concern with experimentation and lack of interest in acupuncture (p < 0.05). CONCLUSIONS: Although nearly half of the respondents reported WTP, significant barriers to participation exist and differ among subgroups. Research addressing these barriers is needed to ensure effective accrual and improve the representation of individuals from diverse backgrounds.

Terapia por Acupuntura/psicologia , Neoplasias da Mama/terapia , Ensaios Clínicos como Assunto/psicologia , Coleta de Dados , Conhecimentos, Atitudes e Prática em Saúde , Participação do Paciente/psicologia , Recusa de Participação/psicologia , Idoso , Atitude , Neoplasias da Mama/etnologia , Neoplasias da Mama/psicologia , Grupos de Populações Continentais/psicologia , Estudos Transversais , Escolaridade , Feminino , Experimentação Humana , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recusa de Participação/etnologia