Project description:Structural birth defects are the leading cause of infant mortality in the US and Europe. Among these, congenital heart disease (CHD) is the most common. Historically, Xenopus, mouse, and pig have provided models for CHD. However, it remains unknown what proteins and pathways are conserved between these species and human. Furthermore, the proteome driving the differences between three-chambered (Xenopus) and four-chambered (mammalian) hearts is unknown. Comparative proteomics of heart tissue from species at different evolutionary points can reveal molecular processes underlying heart function. We examined heart tissue proteomes of Xenopus tropicalis, Xenopus laevis, Mus musculus, and Sus scrofa and assessed protein expression changes in the context of pathways and protein complexes, and enrichment of corresponding genes in human heart diseases.
Project description:Missing data are a pervasive problem in health investigations. We describe some background of missing data analysis and criticize ad hoc methods that are prone to serious problems. We then focus on multiple imputation, in which missing cases are first filled in by several sets of plausible values to create multiple completed datasets, then standard complete-data procedures are applied to each completed dataset, and finally the multiple sets of results are combined to yield a single inference. We introduce the basic concepts and general methodology and provide some guidance for application. For illustration, we use a study assessing the effect of cardiovascular diseases on hospice discussion for late stage lung cancer patients.
Project description:According to estimates from Public Health England, by 2034 70% of adults are expected to be overweight or obese, therefore understanding the underpinning aetiology is a priority. Eating in response to negative affect contributes towards obesity, however, little is known about the underlying mechanisms. Evidence that visceral afferent signals contribute towards the experience of emotion is accumulating rapidly, with the emergence of new influential models of 'active inference'. No longer viewed as a 'bottom up' process, new interoceptive facets based on 'top down' predictions have been proposed, although at present it is unclear which aspects of interoception contribute to aberrant eating behaviour and obesity. Study one examined the link between eating behaviour, body mass index and the novel interoceptive indices; interoceptive metacognitive awareness (IAw) and interoceptive prediction error (IPE), as well as the traditional measures; interoceptive accuracy (IAc) and interoceptive sensibility (IS). The dissociation between these interoceptive indices was confirmed. Emotional eaters were characterised by a heightened interoceptive signal but reduced meta-cognitive awareness of their interoceptive abilities. In addition, emotional eating correlated with IPE; effects that could not be accounted for by differences in anxiety and depression. Study two confirmed the positive association between interoceptive accuracy and emotional eating using a novel unbiased heartbeat discrimination task based on the method of constant stimuli. Results reveal new and important mechanistic insights into the processes that may underlie problematic affect regulation in overweight populations.
Project description:Cardiogenesis in mammals requires exquisite control of gene expression and faulty regulation of transcriptional programs underpins congenital heart disease (CHD), the most common defect among live births. Similarly, many adult cardiac diseases involve transcriptional changes and sometimes have a developmental basis. Long non-coding RNAs (lncRNAs) are a novel class of transcripts that regulate cellular processes by controlling gene expression; however, detailed insights into their biological and mechanistic functions are only beginning to emerge. Here, we discuss recent findings suggesting that lncRNAs are important factors in regulation of mammalian cardiogenesis and in the pathogenesis of CHD as well as adult cardiac disease. We also outline potential methodological and conceptual considerations for future studies of lncRNAs in the heart and other contexts.
Project description:Heart failure is a clinical syndrome caused by dysregulated calcium handling and abnormal cardiac pumping capacity. Wahlquist et al. (2014) show that upregulation of microRNA-25 impairs calcium handling leading to pump dysfunction and that targeting microRNA-25 using antisense oligonucleotides reverses pump dysfunction and improves survival in mice with heart failure.
Project description:Objective:To assess the impact of a triage system of emergency department (ED) referrals for outpatient cardiology appointments. Patient and Methods:We implemented a triage system of ED referrals for outpatient cardiology appointments among patients with a cardiovascular chief complaint deemed safe to leave the ED but needing outpatient follow-up. There were 303 and 267 unique patients in the pre-triage implementation and post-triage implementation cohorts, respectively. We collected retrospective billing data to assess ED return visits, hospitalizations, cardiology outpatient visits, and cardiovascular testing. The pre-triage implementation cohort included patients with an ED visit date between January 1, 2014, and December 31, 2014. The post-triage implementation cohort included patients with an ED visit date between July 1, 2015, and June 30, 2016. Results:The triage model reduced the number of ED-referred cardiovascular service appointments by 73.0% (195 of 267 patients). Additionally, the "no-show" rate for appointments decreased from 17.8% (54 of 303 patients) to 7.9% (21 of 267 patients). There was no increase in ED return visits or unplanned hospitalizations in the posttriage cohort. Finally, the triage model was not associated with an increase in resource-intensive cardiovascular testing (eg, imaging stress tests or computed tomography). Conclusion:Triage of ED referrals for outpatient cardiovascular service appointments reduced cardiology appointment utilization with no impact on return ED visits, hospitalizations, or cardiovascular testing.
Project description:Infection with Helicobacter cinaedi can encompass a wide spectrum of clinical manifestations, including fever, rash, endocarditis, osteomyelitis, and meningitis. The present case demonstrates the ability of H cinaedi to masquerade as acute rheumatic fever and represents the first reported case of cardiac tamponade caused by H cinaedi.
Project description:Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Atherosclerosis is directly associated with CVD and is characterized by slow progressing inflammation which results in the deposition and accumulation of lipids beneath the endothelial layer in conductance and resistance arteries. Both chronic inflammation and disease progression have been associated with several risk factors, including but not limited to smoking, obesity, diabetes, genetic predisposition, hyperlipidemia, and hypertension. Currently, despite increasing incidence and significant expense on the healthcare system in both western and developing countries, there is no curative therapy for atherosclerosis. Instead patients rely on surgical intervention to avoid or revert vessel occlusion, and pharmacological management of the aforementioned risk factors. However, neither of these approaches completely resolve the underlying inflammatory environment which perpetuates the disease, nor do they result in plaque regression. As such, immunomodulation could provide a novel therapeutic option for atherosclerosis; shifting the balance from proatherogenic to athero-protective. Indeed, regulatory T-cells (Tregs), which constitute 5-10% of all CD4+ T lymphocytes in the peripheral blood, have been shown to be athero-protective and could function as new targets in both CVD and atherosclerosis. This review aims to give a comprehensive overview about the roles of Tregs in CVD, focusing on atherosclerosis.
Project description:A 69-year-old man presented with a progressively enlarging pulsatile mass in the left side of his chest. Because of a history of an ischemic cardiomyopathy, he had been randomized in 2003 to undergo coronary artery bypass grafting with a Dor procedure, as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Our patient's imaging studies, including a thoracic computed tomogram and transthoracic echocardiogram, were now of concern for left ventricular pseudoaneurysm. He was taken immediately for surgical exploration. Purulent material, with empyema, extended from the anterior chest wall through the chest cavity into the mediastinum, with communication into the pericardial space. Notably, there was no compromise of the left ventricular cavity, and there was no pseudoaneurysm. The chest was copiously irrigated before closure. The epicardial patch placed 10 years earlier in the STICH trial was not thought to be the nidus of the abscess and was therefore not removed. Three months later, the patient presented again, this time with hemorrhagic shock and bleeding from his left anterior thoracotomy site, which we then re-entered. He was found to have a left ventricular pseudoaneurysm with disruption of the ventricular apex. The epicardial felt-and-Dacron patch, placed 10 years previously during his Dor procedure, was found to be infected with Clostridium difficile and was removed. The left ventricular apex was repaired. Whereas C. difficile bacteremia is rare, the seeding of prosthetic cardiac material with delayed presentation, as in this case, is extraordinarily uncommon.