21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

Scientific, legal, and ethical challenges of end-of-life organ procurement in emergency medicine.

PubMed

Rady, Mohamed Y; Verheijde, Joseph L; McGregor, Joan L

2010-09-01

We review (1) scientific evidence questioning the validity of declaring death and procuring organs in heart-beating (i.e., neurological standard of death) and non-heart-beating (i.e., circulatory-respiratory standard of death) donation; (2) consequences of collaborative programs realigning hospital policies to maximize access of procurement coordinators to critically and terminally ill patients as potential donors on arrival in emergency departments; and (3) ethical and legal ramifications of current practices of organ procurement on patients and their families. Relevant publications in peer-reviewed journals and government websites. Scientific evidence undermines the biological criteria of death that underpin the definition of death in heart-beating (i.e., neurological standard) and non-heart-beating (i.e., circulatory-respiratory standard) donation. Philosophical reinterpretation of the neurological and circulatory-respiratory standards in the death statute, to avoid the appearance of organ procurement as an active life-ending intervention, lacks public and medical consensus. Collaborative programs bundle procurement coordinators together with hospital staff for a team-huddle and implement a quality improvement tool for a Rapid Assessment of Hospital Procurement Barriers in Donation. Procurement coordinators have access to critically ill patients during the course of medical treatment with no donation consent and with family or surrogates unaware of their roles. How these programs affect the medical care of these patients has not been studied. Policies enforcing end-of-life organ procurement can have unintended consequences: (1) erosion of care in the patient's best interests, (2) lack of transparency, and (3) ethical and legal ramifications of flawed standards of declaring death. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

PubMed Central

Ivanovitch, Kenzo; Temiño, Susana

2017-01-01

During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. PMID:29202929

klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis

PubMed Central

Steed, Emily; Faggianelli, Nathalie; Roth, Stéphane; Ramspacher, Caroline; Concordet, Jean-Paul; Vermot, Julien

2016-01-01

The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis. PMID:27221222

Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases Coordination between Irregular Cerebral and Cardiac Activities.

PubMed

Sik, Hin Hung; Gao, Junling; Fan, Jicong; Wu, Bonnie Wai Yan; Leung, Hang Kin; Hung, Yeung Sam

2017-05-10

In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities.

Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases Coordination between Irregular Cerebral and Cardiac Activities

PubMed Central

Sik, Hin Hung; Gao, Junling; Fan, Jicong; Wu, Bonnie Wai Yan; Leung, Hang Kin; Hung, Yeung Sam

2017-01-01

In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities. PMID:28518101

Congenital Heart Disease: Guidelines of Care for Children with Special Health Care Needs.

ERIC Educational Resources Information Center

Minnesota State Dept. of Health, Minneapolis. Services for Children with Handicaps.

These guidelines were written to help families coordinate the health care that may be needed by a child with congenital heart disease. The booklet begins with general information about congenital heart disease. It then discusses the goals of health care, the health care team, the importance of periodic health care, and record keeping procedures.…

A Convective Coordinate Approach to Continuum Mechanics with Application to Electrodynamics

DTIC Science & Technology

2013-01-01

7 3. Differential Operators in Curvilinear Spaces 9 3.1 The Covariant...the particles in an arbitrary (perhaps initial or even fictitious) configuration, and a set of spatial coordinates that fixes locations in space (that...of field quantities defined in such spaces . 2.1 The Background Cartesian System Before defining the physical coordinate systems at the heart of this

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Histone methylations in heart development, congenital and adult heart diseases.

PubMed

Zhang, Qing-Jun; Liu, Zhi-Ping

2015-01-01

Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases.

[Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

PubMed

Xue, Run-Qing; Xu, Man; Yu, Xiao-Jiang; Liu, Long-Zhu; Zang, Wei-Jin

2017-10-25

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

Universal ventricular coordinates: A generic framework for describing position within the heart and transferring data.

PubMed

Bayer, Jason; Prassl, Anton J; Pashaei, Ali; Gomez, Juan F; Frontera, Antonio; Neic, Aurel; Plank, Gernot; Vigmond, Edward J

2018-04-01

Being able to map a particular set of cardiac ventricles to a generic topologically equivalent representation has many applications, including facilitating comparison of different hearts, as well as mapping quantities and structures of interest between them. In this paper we describe Universal Ventricular Coordinates (UVC), which can be used to describe position within any biventricular heart. UVC comprise four unique coordinates that we have chosen to be intuitive, well defined, and relevant for physiological descriptions. We describe how to determine these coordinates for any volumetric mesh by illustrating how to properly assign boundary conditions and utilize solutions to Laplace's equation. Using UVC, we transferred scalar, vector, and tensor data between four unstructured ventricular meshes from three different species. Performing the mappings was very fast, on the order of a few minutes, since mesh nodes were searched in a KD tree. Distance errors in mapping mesh nodes back and forth between meshes were less than the size of an element. Analytically derived fiber directions were also mapped across meshes and compared, showing  < 5° difference over most of the ventricles. The ability to transfer gradients was also demonstrated. Topologically variable structures, like papillary muscles, required further definition outside of the UVC framework. In conclusion, UVC can aid in transferring many types of data between different biventricular geometries. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Combined use of UV-labile calcium chelators and calcium-sensitive dyes in a microscope with two light sources influencing different regions in a group of coordinated contracting cardiac myocytes

NASA Astrophysics Data System (ADS)

Pilarczyk, Goetz; Greulich, Karl-Otto

1997-12-01

The coordination of excitation in a biological system of cells such as cardiac myocytes in heart tissue has crucial influence on the function of the entire organ. This coordinated behavior can be visualized in a small group of embryonic cardiac myocytes derived from the hearts of unborn chicken. Loaded with a calcium sensitive dye the excitation can be imaged via the occurring transient rise in cytosolic calcium concentration. It can be shown that in regions with physiological or morphological restrictions the transient rise in cytosolic calcium occurs with a temporal delay compared to the ordinary array of coupled myocytes. The height of the transient rise of cytosolic calcium is related to the ability of the individual cell to participate in the coordinated contraction. The free cytosolic calcium concentration is decreased with the UV-labile calcium, chelator diazo-2. Our setup allows to decrease the free cytosolic calcium in a single cell of the contracting array of cells. This allows us to introduce mismatches in selected regions of the coordinated contraction and to visualize the effects simultaneously.

On the difference of cardiorespiratory synchronisation and coordination

NASA Astrophysics Data System (ADS)

Krause, Harald; Kraemer, Jan F.; Penzel, Thomas; Kurths, Jürgen; Wessel, Niels

2017-09-01

Cardiorespiratory phase synchronisation (CRS) is a type of cardiorespiratory coupling that manifests through a prediliction for heart beats to occur at specific points relative to the phase of the respiratory cycle. It has been under investigation for nearly 20 years, and while it seems to be mostly occurring in relaxed states such as deep sleep and anesthesia, no clear clinical implications have been established. Cardiorespiratory coordination (CRC) is a recent development in this field where the relationship between the respiratory onset and heart beat is analysed in the time domain and the possible relationship of each heart beat is considered for both the previous and the next respiratory onset. This ostensibly closely related effect must not only show relevant information content but also do so independent of CRS in order to be relevant for future studies. In this paper, we investigate CRC and its relation to CRS mainly using graphical and statistical methods on two exemplary datasets: measurements from a pregnant woman participating in a preeclampsia study and those from a man suffering from sleep apnea. We show fundamental differences between the results of both approaches and are able to show a formerly unknown dependency between the heart activity and respiratory rate, potentially indicating heartbeat-initiated inspiration. Despite their differences, methods developed for the quantification of CRS can be adapted to CRC. Completing the comparison is an investigation into the relationship between CRC and respiratory sinus arrhythmia. Similar to previous results for CRS, the two effects are found to be orthogonal, meaning that they can be observed independently or in conjunction.

“It’s Somebody else’s responsibility” - perceptions of general practitioners, heart failure nurses, care home staff, and residents towards heart failure diagnosis and management for older people in long-term care: a qualitative interview study

PubMed Central

2013-01-01

Background Older people in care-facilities may be less likely to access gold standard diagnosis and treatment for heart failure (HF) than non residents; little is understood about the factors that influence this variability. This study aimed to examine the experiences and expectations of clinicians, care-facility staff and residents in interpreting suspected symptoms of HF and deciding whether and how to intervene. Methods This was a nested qualitative study using in-depth interviews with older residents with a diagnosis of heart failure (n=17), care-facility staff (n=8), HF nurses (n=3) and general practitioners (n=5). Results Participants identified a lack of clear lines of responsibility in providing HF care in care-facilities. Many clinical staff expressed negative assumptions about the acceptability and utility of interventions, and inappropriately moderated residents’ access to HF diagnosis and treatment. Care-facility staff and residents welcomed intervention but experienced a lack of opportunity for dialogue about the balance of risks and benefits. Most residents wanted to be involved in healthcare decisions but physical, social and organisational barriers precluded this. An onsite HF service offered a potential solution and proved to be acceptable to residents and care-facility staff. Conclusions HF diagnosis and management is of variable quality in long-term care. Conflicting expectations and a lack of co-ordinated responsibility for care, contribute to a culture of benign neglect that excludes the wishes and needs of residents. A greater focus on rights, responsibilities and co-ordination may improve healthcare quality for older people in care. Trial registration ISRCTN: ISRCTN19781227 PMID:23829674

"It's Somebody else's responsibility" - perceptions of general practitioners, heart failure nurses, care home staff, and residents towards heart failure diagnosis and management for older people in long-term care: a qualitative interview study.

PubMed

Close, Helen; Hancock, Helen; Mason, James M; Murphy, Jerry J; Fuat, Ahmet; de Belder, Mark; Hungin, A Pali S

2013-07-05

Older people in care-facilities may be less likely to access gold standard diagnosis and treatment for heart failure (HF) than non residents; little is understood about the factors that influence this variability. This study aimed to examine the experiences and expectations of clinicians, care-facility staff and residents in interpreting suspected symptoms of HF and deciding whether and how to intervene. This was a nested qualitative study using in-depth interviews with older residents with a diagnosis of heart failure (n=17), care-facility staff (n=8), HF nurses (n=3) and general practitioners (n=5). Participants identified a lack of clear lines of responsibility in providing HF care in care-facilities. Many clinical staff expressed negative assumptions about the acceptability and utility of interventions, and inappropriately moderated residents' access to HF diagnosis and treatment. Care-facility staff and residents welcomed intervention but experienced a lack of opportunity for dialogue about the balance of risks and benefits. Most residents wanted to be involved in healthcare decisions but physical, social and organisational barriers precluded this. An onsite HF service offered a potential solution and proved to be acceptable to residents and care-facility staff. HF diagnosis and management is of variable quality in long-term care. Conflicting expectations and a lack of co-ordinated responsibility for care, contribute to a culture of benign neglect that excludes the wishes and needs of residents. A greater focus on rights, responsibilities and co-ordination may improve healthcare quality for older people in care. ISRCTN19781227.

A Comparison of Biology Majors' Written Arguments across the Curriculum

ERIC Educational Resources Information Center

Schen, Melissa

2013-01-01

Argumentation in science is the process of coordinating theory and evidence to justify conclusions. This practice is at the heart of scientific journal writing and communication, but little is known regarding the argument quality of college science majors, the future scientists. Studies on written arguments at the college level have focused…

Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

EPA Science Inventory

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

PubMed

Ahir, Bhavesh K; Pratten, Margaret K

2014-01-01

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

[Nurse involvement in primary care: it is the key to improve the outcomes in primary and secondary prevention?].

PubMed

Scardi, Sabino; Gori, Pierpaolo; Umari, Paolo

2010-06-01

Difficulties in management of risk factors, lifestyle and medications adherence to achieve secondary prevention of ischemic heart disease were described. Many studies indicate that the benefit of cardiac rehabilitation therapy after acute coronary events is only partially maintained during the following year. Thereafter, new strategies of medical care are needed to improve the long-term outcomes in coronary patients. Nurse co-ordinated, multidisciplinary cardiac rehabilitative programme could help patients to improve their lifestyle, to control their risk factors and to achieve their therapeutic goals for secondary prevention of ischemic heart disease.

Engineering an in vitro organotypic model for studying cardiac hypertrophy.

PubMed

Jain, Aditi; Hasan, Jafar; Desingu, Perumal Arumugam; Sundaresan, Nagalingam R; Chatterjee, Kaushik

2018-05-01

Neonatal cardiomyocytes cultured on flat surfaces are commonly used as a model to study cardiac failure of diverse origin. A major drawback of such a system is that the cardiomyocytes do not exhibit alignment, organization and calcium transients, similar to the native heart. Therefore, there is a need to develop in vitro platforms that recapitulate the cellular microenvironment of the murine heart as organotypic models to study cardiovascular diseases. In this study, we report an engineered platform that mimics cardiac cell organization and function of the heart. For this purpose, microscale ridges were fabricated on silicon using ultraviolet lithography and reactive ion etching techniques. Physical characterization of the microstructures was done using scanning electron microscopy and atomic force microscopy. Cardiomyocytes grown on these micro-ridges showed global parallel alignment and elliptical nuclear morphology as observed in the heart. Interestingly, calcium currents traversed the engineered cardiomyocytes in a coordinated and directional manner. Moreover, the cardiomyocytes on the engineered substrates were found to be responsive to hypertrophic stimuli, as observed by the expression of a fetal gene, atrial natriuretic peptide and increase in calcium transients upon agonist treatment. Taken together, our work demonstrates that micro-ridges can be used to obtain cardiomyocyte response in vitro, which closely resembles mammalian heart. Copyright © 2018 Elsevier B.V. All rights reserved.

Who is Responsible for Training the Civilian Members of the Provincial Reconstruction Teams (PRTs)

DTIC Science & Technology

2010-05-01

Quoted from an interview conducted by AI. Hemingway , "CORDS: Winning Hearts and Minds in Vietnam," Vietnam Magazine, (February 1994). 82 Brig. Gen Dinh...Team-a model for coordination." Air University Review, July-August 1967. Hemingway , AI. "CORDS: Winning Hearts and Minds in Vietnam." Vietnam Magazine

Management of end-stage heart failure: a perspective on the Arab Gulf states

PubMed Central

Al Habeeb, Waleed; Stewart, Garrick C.; Mudge, Gilbert H.

2009-01-01

The ever expanding epidemic of end-stage heart failure represents one of the greatest challenges of modern cardiovascular medicine. With medical treatments hampered by significant limitations, physicians caring for patients with advanced heart disease have turned to cardiac transplantation and durable mechanical circulatory assist devices as definitive therapies. These advanced therapeutic modalities are not widely available outside the United States and Europe, but nevertheless offer enormous potential for patients in the Arab Gulf suffering from end-stage heart failure. This review will discuss the management of end-stage heart failure in the Gulf States, with an emphasis on therapies best utilized within a framework of regional cooperation and coordination. PMID:19847084

Poster - Thur Eve - 26: Interfraction reproducibility of heart position during breast irradiation using Active Breathing Control.

PubMed

Comsa, D; Zhang, B; Mosely, D; Yeung, I

2012-07-01

The moderate deep-inspiration breath hold (mDIBH) technique using the Active Breathing Coordinator (ABC) from Elekta is used in our clinic to lower the heart dose during left breast irradiations. The purpose of this work was to investigate the interfraction reproducibility of the heart to chest distance during these treatments and to evaluate the dosimetric effect of any changes in the heart position. Daily CBCT images were available for 5 patients who had been treated with ABC tangents and a cavity boost. On these images, one-dimensional measurements of the distance between the heart and the chest wall were taken at two anatomical locations corresponding roughly with the location where the radiation field most likely intercepts the heart. The average change in this distance was interpreted as a shift of the heart position. To assess the effect of this shift on the delivered heart dose, the heart contours in the clinical plans of the corresponding patients were shifted towards the treatment field using standard Pinnacle tools. Although the ABC device allows good reproducibility of the volume of air held, this does not warrant reproducibility of heart position for all patients during treatment. The largest average heart shift extracted from CBCT images in this study was 6.2mm. The heart dose reconstructed using this shift for the corresponding patient also showed the largest effect. However, even in the presence of a systematic heart shift of this magnitude, the ABC plan still showed superior heart dose reduction compared to the free-breathing plan. © 2012 American Association of Physicists in Medicine.

The Evaluation of a Regional Faith Community Network's Million Hearts Program.

PubMed

Cooper, Jennifer; Zimmerman, Wendy

2016-01-01

The goal of the Million Hearts initiative is to prevent one million heart attacks and strokes by 2017. Maryland was one state in the Association of State and Territorial Health Official's Million Hearts State Learning Collaborative. Washington County, Maryland formed a collaboration between the County Health Department, Meritus Health System, and the Meritus Health Parish Nurse Coordinator to address hypertension in the county. Within a regional network of 52 faith communities, the Parish Nurse Coordinator recruited 25 faith community nurses to participate in a three-month program. Nurses were trained on proper blood pressure measurement and 22 nurses identified 58 participants engaged in blood pressure self-monitoring and coaching for lifestyle changes. Additionally, nurses took 1,729 blood pressures and provided health education to individuals within their congregations. Fifty-one participants participated in blood pressure self-monitoring and lifestyle coaching with faith community nurses. There was improvement in six out of seven lifestyle areas. Eight-two percent of participants (N = 42) decreased their systolic and/or diastolic blood pressure over three months. Coaching provided by faith community nurses can create an environment of sustained support to promote improved lifestyle and blood pressure changes over time. © 2015 Wiley Periodicals, Inc.

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

PubMed Central

Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

2017-01-01

Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

Electrical wave propagation in an anisotropic model of the left ventricle based on analytical description of cardiac architecture.

PubMed

Pravdin, Sergey F; Dierckx, Hans; Katsnelson, Leonid B; Solovyova, Olga; Markhasin, Vladimir S; Panfilov, Alexander V

2014-01-01

We develop a numerical approach based on our recent analytical model of fiber structure in the left ventricle of the human heart. A special curvilinear coordinate system is proposed to analytically include realistic ventricular shape and myofiber directions. With this anatomical model, electrophysiological simulations can be performed on a rectangular coordinate grid. We apply our method to study the effect of fiber rotation and electrical anisotropy of cardiac tissue (i.e., the ratio of the conductivity coefficients along and across the myocardial fibers) on wave propagation using the ten Tusscher-Panfilov (2006) ionic model for human ventricular cells. We show that fiber rotation increases the speed of cardiac activation and attenuates the effects of anisotropy. Our results show that the fiber rotation in the heart is an important factor underlying cardiac excitation. We also study scroll wave dynamics in our model and show the drift of a scroll wave filament whose velocity depends non-monotonically on the fiber rotation angle; the period of scroll wave rotation decreases with an increase of the fiber rotation angle; an increase in anisotropy may cause the breakup of a scroll wave, similar to the mother rotor mechanism of ventricular fibrillation.

Effectiveness of Healthcare Coordination in Patients with Chronic Respiratory Diseases.

PubMed

Kurpas, Donata; Szwamel, Katarzyna; Lenarcik, Dorota; Guzek, Marika; Prusaczyk, Artur; Żuk, Paweł; Michalowska, Jolanta; Grzeda, Agnieszka; Mroczek, Bożena

2017-08-12

Coordination of healthcare effectively prevents exacerbations and reduces the number of hospitalizations, emergency visits, and the mortality rate in patients with chronic respiratory diseases. The purpose of this study was to determine clinical effectiveness of ambulatory healthcare coordination in chronic respiratory patients and its effect on the level of healthcare services as an indicator of direct medical costs. We conducted a retrospective health record survey, using an online database of 550 patients with chronic respiratory diseases. There were decreases in breathing rate, heart rate, and the number of cigarettes smoked per day, and forced vital capacity (FVC) and forced expired volume in 1 s (FEV1) increased after the implementation of the coordinated healthcare structure. These benefits were accompanied by increases in the number of visits to the pulmonary outpatient clinic (p < 0.001), diagnostic costs (p < 0.001), and referrals to other outpatient clinics (p < 0.003) and hospitals (p < 0.001). The advantageous effects of healthcare coordination on clinical status of respiratory patients above outlined persisted over a 3-year period being reviewed.

Human Energy Expenditure and Postural Coordination on the Mechanical Horse.

PubMed

Baillet, Héloïse; Thouvarecq, Régis; Vérin, Eric; Tourny, Claire; Benguigui, Nicolas; Komar, John; Leroy, David

2017-01-01

The authors investigated and compared the energy expenditure and postural coordination of two groups of healthy subjects on a mechanical horse at 4 increasing oscillation frequencies. Energy expenditure was assessed from the oxygen consumption, respiratory quotient, and heart rate values, and postural coordination was characterized by relative phase computations between subjects (elbow, head, trunk) and horse. The results showed that the postural coordination of the riders was better adapted (i.e., maintenance of in-phase and antiphase) than that of the nonriders, but the energy expenditure remains the same. Likewise, we observed an energy system shifting only for nonriders (from aerobic to lactic anaerobic mode). Finally, cross-correlations showed a link between energy expenditure and postural coordination in the riders (i.e., effectiveness).

[Reduction of rehospitalisation on elderly heart failure patients: A retrospective cohort VISage network].

PubMed

Labranche, D; Mestre-Fernandes, C; Delahaye, F; Sanchez, S

2016-11-01

Heart failure was a public health problem for one million of French patients. Patients are particularly concerned in rehospitalisation for this chronic pathology. A specific healthcare network was created to take care of patients with heart failure directly at home. This healthcare network (named VISage) brings a specific and adapted monitoring in heart failure. The main of this study was to evaluate the impact of healthcare network in rehospitalisation rate for heart failure of patients. We conducted a retrospective cohort study with patients' hospital files of the CH Vienne. Patients who were included in our healthcare network (VISage) were screened. Primary endpoint was 30days, 6 months, and 1year rehospitalisation rate for heart failure before and after using healthcare network. One hundred and four patients with comorbidities were included between February 2009 and November 2015. A significant reduction of rehospitalisation rate for heart failure was observed before and after network: 0.65 (±0.52) vs. 0.17 (±0.43) 30days, 1.17 (±0.74) vs. 0.42 (±0.71) at 6 months and 1.35 (±0.95) vs. 0.47 (±0.74) at 1 year (P<0.0001). Results were significant for global rehospitalisation rate too. No significant differences were shown on hospital length of stay. Coordinated healthcare by a specific network at home for elderly is benefic for the rehospitalisation rate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Adult congenital heart disease nurse coordination: Essential skills and role in optimizing team-based care a position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

PubMed

Sillman, Christina; Morin, Joanne; Thomet, Corina; Barber, Deena; Mizuno, Yoshiko; Yang, Hsiao-Ling; Malpas, Theresa; Flocco, Serena Francesca; Finlay, Clare; Chen, Chi-Wen; Balon, Yvonne; Fernandes, Susan M

2017-02-15

Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with congenital heart disease (CHD) worldwide. Among ISACHD's objectives is to "promote a holistic team-based approach to the care of the adult with CHD that is comprehensive, patient-centered, and interdisciplinary" (http://www.isachd.org). This emphasis on team-based care reflects the fact that adults with CHD constitute a heterogeneous population with a wide spectrum of disease complexity, frequent association with other organ involvement, and varied co-morbidities and psychosocial issues. Recognizing the vital role of the adult CHD (ACHD) nurse coordinator (ACHD-NC) in optimizing team-based care, ISACHD established a task force to elucidate and provide guidance on the roles and responsibilities of the ACHD-NC. Acknowledging that nursing roles can vary widely from region to region based on factors such as credentials, scopes of practice, regulations, and local culture and tradition, an international panel was assembled with experts from North America, Europe, East Asia, and Oceania. The writing committee was tasked with reviewing key aspects of the ACHD-NC's role in team-based ACHD care. The resulting ISACHD position statement addresses the ACHD-NC's role and skills required in organizing, coordinating, and facilitating the care of adults with CHD, holistic assessment of the ACHD patient, patient education and counseling, and support for self-care management and self-advocacy. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Classification and Quality Standards of Heart Failure Units: Scientific Consensus of the Spanish Society of Cardiology.

PubMed

Anguita Sánchez, Manuel; Lambert Rodríguez, José Luis; Bover Freire, Ramón; Comín Colet, Josep; Crespo Leiro, María G; González Vílchez, Francisco; Manito Lorite, Nicolás; Segovia Cubero, Javier; Ruiz Mateas, Francisco; Elola Somoza, Francisco Javier; Íñiguez Romo, Andrés

2016-10-01

The prevalence of heart failure remains high and represents the highest disease burden in Spain. Heart failure units have been developed to systematize the diagnosis, treatment, and clinical follow-up of heart failure patients, provide a structure to coordinate the actions of various entities and personnel involved in patient care, and improve prognosis and quality of life. There is ample evidence on the benefits of heart failure units or programs, which have become widespread in Spain. One of the challenges to the analysis of heart failure units is standardization of their classification, by determining which "programs" can be identified as heart failure "units" and by characterizing their complexity level. The aim of this article was to present the standards developed by the Spanish Society of Cardiology to classify and establish the requirements for heart failure units within the SEC-Excellence project. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Sex-related differences in the thanatomicrobiome in postmortem heart samples using bacterial gene regions V1-2 and V4.

PubMed

Bell, Courtnee R; Wilkinson, Jeremy E; Robertson, Boakai K; Javan, Gulnaz T

2018-05-10

Recent studies have revealed distinct thanatomicrobiome (microbiome of death) signatures in human body sites after death. Thanatomicrobiome studies suggest that microbial succession after death may have the potential to reveal important postmortem biomarkers for the identification of time of death. We surveyed the postmortem microbiomes of cardiac tissues from ten corpses with varying times of death (6-58 h) using amplicon-based sequencing of the 16S rRNA gene' V1-2 and V4 hypervariable regions. The results demonstrated that amplicons had statistically significant (p <0.05) sex-dependent changes. Clostridium sp., Pseudomonas sp., Pantoea sp., and Streptococcus sp. had the highest enrichment for both V1-2 and V4 regions. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female hearts compared to males. Additionally, Streptococcus sp. was solely found in male heart samples. The distinction between sexes was further supported by Principle Coordinate Analysis, which revealed microbes in female hearts formed a distinctive cluster separate from male cadavers for both hypervariable regions. This study provides data that demonstrates that two hypervariable regions show discriminatory power for sex differences in postmortem heart samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Characteristics of the patients with heart disease in a health area of A Coruña province. Barbanza 2000 study].

PubMed

2003-12-01

The results of the Barbanza study are presented, a cross-sectional study carried out in an area of primary care level of the southwest of A Coruña province and relative to the situation of the cardiovascular diseases. Demographic, clinical, blood pressure and therapeutic data corresponding to the patients cared during a period of 2 months by 21 primary care physicians were registered prospectively in an uniformized questionnaire. 31% of the total sample of 6,325 patients suffered hypertension and 13.4% showed past history of heart disease. Hypertension was observed in 71% of the patients with heart failure, in 69% of the patients who showed ischemic cardiopathy (angina and myocardial infarction) and in 67% of the patients with atrial fibrillation. More than 50% of the hypertensive patients with heart disease (heart failure, ischemic heart disease and atrial fibrillation) showed values of systolic blood pressure which are equal or greater than 140 mmHg. 90% of the patients with ischemic cardiopathy showed values of LDL cholesterol higher than 100 mg/dl and 65% higher than 130 mg/dl. 54.8% of the patients with heart failure was receiving treatment with an inhibitor of the angiotensin converting enzyme; 27.2% of the patients with ischemic cardiopathy received treatment with a beta-blocker, and 32% of the patients with atrial fibrillation received anticoagulants. The heart failure, the ischemic cardiopathy, and the atrial fibrillation are associated with great frequency to hypertension. Control of the blood pressure in the hypertensive patients with heart disease is very limited. The utilization of drugs of obligatory use in hypertensives with heart disease is limited. It is necessary to promote strategies of information and coordination between the primary and specialized care to improve the care of the patients with cardiovascular disease.

[Statocyst regulation of the heart and statokinetic reflexes in the crab, Hemigrapsus sanguineus, during linear acceleration].

PubMed

Kuntsova, M Ia; Sveshnikov, V G; Timofeeva, E V

1978-01-01

In experiments on the shore crab H. sanguineus studies have been made of the effect of variable longitudinal acceleration during swinging (for 15--30 min) upon cardiac activity and gravitational reflexes. High sensitivity of gravitational receptors of the canal statocyst to the effect of acceleration was demonstrated. Removal of the statocysts increases the frequency and amplitude of cardiac contractions as revealed by ECG recording. Changes in stato-kinetic coordinations cause both the disorder of overturning reactions and the disorder of reciprocal inhibition in antagonistic muscles of the dactylopodite. Statocyst regulation of skeletal muscles and heart is presumably realised via contralateral inhibitory canal which is sensitive to linear accelerations.

Cardiac torsion and electromagnetic fields: the cardiac bioinformation hypothesis.

PubMed

Burleson, Katharine O; Schwartz, Gary E

2005-01-01

Although in physiology the heart is often referred to as a simple piston pump, there are in fact two additional features that are integral to cardiac physiology and function. First, the heart as it contracts in systole, also rotates and produces torsion due to the structure of the myocardium. Second, the heart produces a significant electromagnetic field with each contraction due to the coordinated depolarization of myocytes producing a current flow. Unlike the electrocardiogram, the magnetic field is not limited to volume conduction and extends outside the body. The therapeutic potential for interaction of this cardioelectromagnetic field both within and outside the body is largely unexplored. It is our hypothesis that the heart functions as a generator of bioinformation that is central to normative functioning of body. The source of this bioinformation is based on: (1) vortex blood flow in the left ventricle; (2) a cardiac electromagnetic field and both; (3) heart sounds; and (4) pulse pressure which produce frequency and amplitude information. Thus, there is a multidimensional role for the heart in physiology and biopsychosocial dynamics. Recognition of these cardiac properties may result in significant implications for new therapies for cardiovascular disease based on increasing cardiac energy efficiency (coherence) and bioinformation from the cardioelectromagnetic field. Research studies to test this hypothesis are suggested.

Nurse-coordinated collaborative disease management improves the quality of guideline-recommended heart failure therapy, patient-reported outcomes, and left ventricular remodelling.

PubMed

Güder, Gülmisal; Störk, Stefan; Gelbrich, Goetz; Brenner, Susanne; Deubner, Nikolas; Morbach, Caroline; Wallenborn, Julia; Berliner, Dominik; Ertl, Georg; Angermann, Christiane E

2015-04-01

Heart failure (HF) pharmacotherapy is often not prescribed according to guidelines. This longitudinal study investigated prescription rates and dosages of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA), and concomitant changes of symptoms, echocardiographic parameters of left ventricular (LV) function and morphology and results of the Short Form-36 (SF-36) Health Survey in participants of the Interdisciplinary Network Heart Failure (INH) programme. The INH study evaluated a nurse-coordinated management, HeartNetCare-HF(TM) (HNC), against Usual Care (UC) in patients hospitalized for decompensated HF [LV ejection fraction (LVEF) ≤40% before discharge). A total of 706 subjects surviving >18 months (363 UC, 343 HNC) were examined 6-monthly. At baseline, 92% received ACEi/ARB, (HNC/UC 91/93%, P = 0.28), 86% received beta-blockers (86/86%, P = 0.83), and 44% received MRA (42/47%, P = 0.07). After 18 months, beta-blocker use had increased only in HNC (+7.6%, P < 0.001). Guideline-recommended target doses were achieved more frequently in HNC for ACEi/ARB (HNC/UC: 50/25%, P < 0.001) and beta-blockers (39/15%, P < 0.001). The following variables were more improved and/or better in subjects undergoing HNC compared with UC: LVEF (47 ± 12 vs. 44 ± 12%, P = 0.004, change +17/+14%, P = 0.010), LV end-diastolic diameter (59 ± 9 vs. 61 ± 9.6 mm, P = 0.024, change -2.3/-1.4 mm, P = 0.13), New York Heart Association class (1.9 ± 0.7 vs. 2.1 ± 0.7, P = 0.001, change -0.44/-0.25, P = 0.002) and SF-36 physical component summary score (41.6 ± 11.2 vs. 38.5 ± 11.8, P = 0.004, change +3.3 vs. +1.1 score points, P < 0.02). Prescription rates and dosages of ACEi/ARB and beta-blockers improved more in HNC than UC patients. Concomitantly, participation in HNC was associated with significantly better clinical outcomes and more favourable echocardiographic changes after 18 months. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Care management for low-risk patients with heart failure: a randomized, controlled trial.

PubMed

DeBusk, Robert Frank; Miller, Nancy Houston; Parker, Kathleen Marie; Bandura, Albert; Kraemer, Helena Chmura; Cher, Daniel Joseph; West, Jeffrey Alan; Fowler, Michael Bruce; Greenwald, George

2004-10-19

Nurse care management programs for patients with chronic illness have been shown to be safe and effective. To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period. Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001. 5 northern California hospitals in a large health maintenance organization. Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care). Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians. Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death. At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]). The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor. Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.

Strategy for Upgrading Preparedness in Small and Rural Communities to Meet National Preparedness Standards

DTIC Science & Technology

2010-12-01

National Academy of Public Administration NEMA National Emergency Managers Association xii NICC National Infrastructure Coordinating Center NIMS...2003, p. 3). A blunt conclusion stated succinctly in the 2008 study conducted by the National Emergency Managers Association ( NEMA ) on barriers to...NIMS compliance speaks to the heart of the issue: “Poorer, rural states can’t meet implementation, training, compliance requirements” ( NEMA , 2008

Metabolic circadian rhythms in embryonic turtles.

PubMed

Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

2013-07-01

Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest.

National Center on Sleep Disorders Research

MedlinePlus

... for Updates The National Center on Sleep Disorders Research (NCSDR) Located within the National Heart, Lung, and ... key functions: research, training, technology transfer, and coordination. Research Sleep disorders span many medical fields, requiring multidisciplinary ...

Electrical Wave Propagation in an Anisotropic Model of the Left Ventricle Based on Analytical Description of Cardiac Architecture

PubMed Central

Pravdin, Sergey F.; Dierckx, Hans; Katsnelson, Leonid B.; Solovyova, Olga; Markhasin, Vladimir S.; Panfilov, Alexander V.

2014-01-01

We develop a numerical approach based on our recent analytical model of fiber structure in the left ventricle of the human heart. A special curvilinear coordinate system is proposed to analytically include realistic ventricular shape and myofiber directions. With this anatomical model, electrophysiological simulations can be performed on a rectangular coordinate grid. We apply our method to study the effect of fiber rotation and electrical anisotropy of cardiac tissue (i.e., the ratio of the conductivity coefficients along and across the myocardial fibers) on wave propagation using the ten Tusscher–Panfilov (2006) ionic model for human ventricular cells. We show that fiber rotation increases the speed of cardiac activation and attenuates the effects of anisotropy. Our results show that the fiber rotation in the heart is an important factor underlying cardiac excitation. We also study scroll wave dynamics in our model and show the drift of a scroll wave filament whose velocity depends non-monotonically on the fiber rotation angle; the period of scroll wave rotation decreases with an increase of the fiber rotation angle; an increase in anisotropy may cause the breakup of a scroll wave, similar to the mother rotor mechanism of ventricular fibrillation. PMID:24817308

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology

PubMed Central

Roncaglia, Paola; Howe, Douglas G.; Laulederkind, Stanley J.F.; Khodiyar, Varsha K.; Berardini, Tanya Z.; Tweedie, Susan; Foulger, Rebecca E.; Osumi-Sutherland, David; Campbell, Nancy H.; Huntley, Rachael P.; Talmud, Philippa J.; Blake, Judith A.; Breckenridge, Ross; Riley, Paul R.; Lambiase, Pier D.; Elliott, Perry M.; Clapp, Lucie; Tinker, Andrew; Hill, David P.

2018-01-01

Background: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. Methods and Results: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. Conclusions: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. PMID:29440116

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

PubMed

Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P

2018-02-01

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.

Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study.

PubMed

Angermann, Christiane E; Störk, Stefan; Gelbrich, Götz; Faller, Hermann; Jahns, Roland; Frantz, Stefan; Loeffler, Markus; Ertl, Georg

2012-01-01

Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30; P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding New York Heart Association class (P=0.05), physical functioning (P=0.03), and physical health component (P=0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure-related issues. The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.

[A health passport for patients with heart failure].

PubMed

Turpeau, Stéphanie

2017-11-01

The health passport gives concrete form to the patient's care project. It constitutes a tool for sharing information between the community and hospital centred on and kept by the patient. It favours coordination between the different professionals involved in the care of patients with heart failure. Given to all patients from the beginning of their treatment, this personalised care programme enables the proposed treatment to be formalised. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Augmented reality image guidance for minimally invasive coronary artery bypass

NASA Astrophysics Data System (ADS)

Figl, Michael; Rueckert, Daniel; Hawkes, David; Casula, Roberto; Hu, Mingxing; Pedro, Ose; Zhang, Dong Ping; Penney, Graeme; Bello, Fernando; Edwards, Philip

2008-03-01

We propose a novel system for image guidance in totally endoscopic coronary artery bypass (TECAB). A key requirement is the availability of 2D-3D registration techniques that can deal with non-rigid motion and deformation. Image guidance for TECAB is mainly required before the mechanical stabilization of the heart, thus the most dominant source of non-rigid deformation is the motion of the beating heart. To augment the images in the endoscope of the da Vinci robot, we have to find the transformation from the coordinate system of the preoperative imaging modality to the system of the endoscopic cameras. In a first step we build a 4D motion model of the beating heart. Intraoperatively we can use the ECG or video processing to determine the phase of the cardiac cycle. We can then take the heart surface from the motion model and register it to the stereo-endoscopic images of the da Vinci robot using 2D-3D registration methods. We are investigating robust feature tracking and intensity-based methods for this purpose. Images of the vessels available in the preoperative coordinate system can then be transformed to the camera system and projected into the calibrated endoscope view using two video mixers with chroma keying. It is hoped that the augmented view can improve the efficiency of TECAB surgery and reduce the conversion rate to more conventional procedures.

Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.

PubMed

Spokoyny, Ilana; Lansberg, Maarten; Thiessen, Rosita; Kemp, Stephanie M; Aksoy, Didem; Lee, YongJae; Mlynash, Michael; Hirsch, Karen G

2016-10-01

Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields. © 2016 American Heart Association, Inc.

Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease.

PubMed

Kathiriya, I S; Srivastava, D

2000-01-01

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

Development of multiscale complexity and multifractality of fetal heart rate variability.

PubMed

Gierałtowski, Jan; Hoyer, Dirk; Tetschke, Florian; Nowack, Samuel; Schneider, Uwe; Zebrowski, Jan

2013-11-01

During fetal development a complex system grows and coordination over multiple time scales is formed towards an integrated behavior of the organism. Since essential cardiovascular and associated coordination is mediated by the autonomic nervous system (ANS) and the ANS activity is reflected in recordable heart rate patterns, multiscale heart rate analysis is a tool predestined for the diagnosis of prenatal maturation. The analyses over multiple time scales requires sufficiently long data sets while the recordings of fetal heart rate as well as the behavioral states studied are themselves short. Care must be taken that the analysis methods used are appropriate for short data lengths. We investigated multiscale entropy and multifractal scaling exponents from 30 minute recordings of 27 normal fetuses, aged between 23 and 38 weeks of gestational age (WGA) during the quiet state. In multiscale entropy, we found complexity lower than that of non-correlated white noise over all 20 coarse graining time scales investigated. Significant maturation age related complexity increase was strongest expressed at scale 2, both using sample entropy and generalized mutual information as complexity estimates. Multiscale multifractal analysis (MMA) in which the Hurst surface h(q,s) is calculated, where q is the multifractal parameter and s is the scale, was applied to the fetal heart rate data. MMA is a method derived from detrended fluctuation analysis (DFA). We modified the base algorithm of MMA to be applicable for short time series analysis using overlapping data windows and a reduction of the scale range. We looked for such q and s for which the Hurst exponent h(q,s) is most correlated with gestational age. We used this value of the Hurst exponent to predict the gestational age based only on fetal heart rate variability properties. Comparison with the true age of the fetus gave satisfying results (error 2.17±3.29 weeks; p<0.001; R(2)=0.52). In addition, we found that the normally used DFA scale range is non-optimal for fetal age evaluation. We conclude that 30 min recordings are appropriate and sufficient for assessing fetal age by multiscale entropy and multiscale multifractal analysis. The predominant prognostic role of scale 2 heart beats for MSE and scale 39 heart beats (at q=-0.7) for MMA cannot be explored neither by single scale complexity measures nor by standard detrended fluctuation analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Nurses' strategies to address self-care aspects related to medication adherence and symptom recognition in heart failure patients: an in-depth look.

PubMed

Jaarsma, Tiny; Nikolova-Simons, Mariana; van der Wal, Martje H L

2012-01-01

Despite an increasing body of knowledge on self-care in heart failure patients, the need for effective interventions remains. We sought to deepen the understanding of interventions that heart failure nurses use in clinical practice to improve patient adherence to medication and symptom monitoring. A qualitative study with a directed content analysis was performed, using data from a selected sample of Dutch-speaking heart failure nurses who completed booklets with two vignettes involving medication adherence and symptom recognition. Nurses regularly assess and reassess patients before they decide on an intervention. They evaluate basic/factual information and barriers in a patient's behavior, and try to find room for improvement in a patient's behavior. Interventions that heart failure nurses use to improve adherence to medication and symptom monitoring were grouped into the themes of increasing knowledge, increasing motivation, and providing patients with practical tools. Nurses also described using technology-based tools, increased social support, alternative communication, partnership approaches, and coordination of care to improve adherence to medications and symptom monitoring. Despite a strong focus on educational strategies, nurses also reported other strategies to increase patient adherence. Nurses use several strategies to improve patient adherence that are not incorporated into guidelines. These interventions need to be evaluated for further applications in improving heart failure management. Copyright © 2012 Elsevier Inc. All rights reserved.

Addressing the conundrum of multimorbidity in heart failure: Do we need a more strategic approach to improve health outcomes?

PubMed

Stewart, Simon; Riegel, Barbara; Thompson, David R

2016-02-01

There is clear evidence across the globe that the clinical complexity of patients presenting to hospital with the syndrome of heart failure is increasing - not only in terms of the presence of concurrent disease states, but with additional socio-demographic risk factors that complicate treatment. Management strategies that treat heart failure as the main determinant of health outcomes ignores the multiple and complex issues that will inevitably erode the efficacy and efficiency of current heart failure management programmes. This complex problem (or conundrum) requires a different way of thinking around the complex interactions that underpin poor outcomes in heart failure. In this context, we present the COordinated NUrse-led inteNsified Disease management for continuity of caRe for mUltiMorbidity in Heart Failure (CONUNDRUM-HF) matrix that may well inform future research and models of care to achieve better health outcomes in this rapidly increasing patient population. © The European Society of Cardiology 2015.

Interactive visualization for scar transmurality in cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Reiml, Sabrina; Toth, Daniel; Panayiotou, Maria; Fahn, Bernhard; Karim, Rashed; Behar, Jonathan M.; Rinaldi, Christopher A.; Razavi, Reza; Rhode, Kawal S.; Brost, Alexander; Mountney, Peter

2016-03-01

Heart failure is a serious disease affecting about 23 million people worldwide. Cardiac resynchronization therapy is used to treat patients suffering from symptomatic heart failure. However, 30% to 50% of patients have limited clinical benefit. One of the main causes is suboptimal placement of the left ventricular lead. Pacing in areas of myocardial scar correlates with poor clinical outcomes. Therefore precise knowledge of the individual patient's scar characteristics is critical for delivering tailored treatments capable of improving response rates. Current research methods for scar assessment either map information to an alternative non-anatomical coordinate system or they use the image coordinate system but lose critical information about scar extent and scar distribution. This paper proposes two interactive methods for visualizing relevant scar information. A 2-D slice based approach with a scar mask overlaid on a 16 segment heart model and a 3-D layered mesh visualization which allows physicians to scroll through layers of scar from endocardium to epicardium. These complementary methods enable physicians to evaluate scar location and transmurality during planning and guidance. Six physicians evaluated the proposed system by identifying target regions for lead placement. With the proposed method more target regions could be identified.

Electronic Tool for Distribution and Allocation of Heart on Donation and Transplantation in Mexico.

PubMed

Maqueda Tenorio, S E; Meixueiro Daza, L A; Maqueda Estrada, S

2016-03-01

In Mexico and globally, organs and/or tissues donated from deceased people are insufficient to cover the demand for transplants. In 2014, a rate of 3.6 organ donors per million in habitants was recorded; this is reflected in the transplants performed, including heart transplantation, with a rate of 0.4 per million population. According to the legal framework of Mexico, the National Transplant Center is responsible for coordinating National Subsystem of donation and transplantation, and one of its functions is to integrate and backup information regarding donation and transplantation through the National Transplant Registry System. In July 2015, 45 people were registered in the database of patients waiting for a heart transplant, of which 34.61% were female recipients and 65.39% male. Distribution and allocation processes are a key element to provide a fair distribution for those patients waiting for that organ; thus the creation of an electronic tool is proposed, one that aims to support the decision of the donation and/or transplants coordination committee by providing the necessary elements to make this process more efficient. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and Evaluation of Methods for Structured Recording of Heart Murmur Findings Using SNOMED-CT® Post-Coordination

PubMed Central

Green, Julie M.; Wilcke, Jeffrey R.; Abbott, Jonathon; Rees, Loren P.

2006-01-01

Objective: This study evaluated an existing SNOMED-CT® model for structured recording of heart murmur findings and compared it to a concept-dependent attributes model using content from SNOMED-CT. Methods: The authors developed a model for recording heart murmur findings as an alternative to SNOMED-CT's use of Interprets and Has interpretation. A micro-nomenclature was then created to support each model using subset and extension mechanisms described for SNOMED-CT. Each micro-nomenclature included a partonomy of cardiac cycle timing values. A mechanism for handling ranges of values was also devised. One hundred clinical heart murmurs were recorded using purpose-built recording software based on both models. Results: Each micro-nomenclature was extended through the addition of the same list of concepts. SNOMED role grouping was required in both models. All 100 clinical murmurs were described using each model. The only major differences between the two models were the number of relationship rows required for storage and the hierarchical assignments of concepts within the micro-nomenclatures. Conclusion: The authors were able to capture 100 clinical heart murmurs with both models. Requirements for implementing the two models were virtually identical. In fact, data stored using these models could be easily interconverted. There is no apparent penalty for implementing either approach. PMID:16501179

Simulation of heart infarction by laser microbeams and induction of arrhythmias by optical tweezers

NASA Astrophysics Data System (ADS)

Perner, Birgit; Monajembashi, Shamci; Rapp, Alexander; Wollweber, Leo; Greulich, Karl Otto

2004-10-01

Laser microbeam and optical tweezers were used for micromanipulation of a heart tissue model consisting of embryonic chicken cardiomyocytes and bibroblasts. Using the laser microbeam a would was created, i.e. a sort of artificial heart infarction was generated. The first steps of wound repair were observed by live cell imaging. A complete filling of teh would primarily by migrating fibroblasts but not by cardiomyocytes was detected 18 hours after wounding. In another set of experiments erythrocyte mediated force application (EMFA) by optical tweezers was applied for optomechanical manipulatoin of cardiomyocytes and fibroblasts. Here we demonstrate induction of dramatic distrubances of calcium waves in a group of synchronously beating cardiomyocytes by an optomechanical input that results in cellular deformation. Surprisingly, it was found that putatively non-excitable fibroblasts respond to this mechanical stress with calcium oscillations. The results reported here indicate that the induction of artificial heart infarction can provide insights into healing processes after mycardial injury. EMFA is capable to examine effects of myocardial overload and to provide important information about processes triggered by mechanical stress on the level of single or very few cells. As a perspective, the preseneted techniques may be used to study the influence of drugs on wound healing and coordination of beating in the heart.

[Differences between German and Turkish-speaking participants in a chronic heart failure management program].

PubMed

Ernstmann, N; Karbach, U

2017-02-01

German and Turkish-speaking patients were recruited for a chronic heart failure management program. So far little is known about the special needs and characteristics of Turkish-speaking patients with chronic heart failure; therefore, the aim of this study was to examine sociodemographic and illness-related differences between German and Turkish-speaking patients with chronic heart failure. German and Turkish-speaking patients suffering from chronic heart failure and insured with the AOK Rheinland/Hamburg or the BARMER GEK health insurance companies and living in Cologne, Germany, were enrolled. Recruitment took place in hospitals, private practices and at information events. Components of the program were coordination of a guideline-oriented medical care, telemonitoring (e.g., blood pressure, electrocardiogram, and weight), a 24-h information hotline, attendance by German and Turkish-speaking nurses and a patient education program. Data were collected by standardized interviews in German or Turkish language. Data were analyzed with descriptive measures and tested for significance differences using Pearson's χ 2 -test and the t‑test. A total of 465 patients (average age 71 years, 55 % male and 33 % Turkish-speaking) were enrolled in the care program during the study period. Significant differences between German and Turkish-speaking patients were found for age, education, employment status, comorbidities, risk perception, knowledge on heart failure and fear of loss of independence. The response rate could be achieved with the help of specific measures for patient enrollment by Turkish-speaking integration nurses. The differences between German and Turkish-speaking patients should in future be taken into account in the care of people with chronic heart failure.

The coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival: a reductase-based peptide counters β-adrenergic receptor ligand-mediated cardiac dysfunction

PubMed Central

Ding, Bo; Gibbs, Peter E. M.; Brookes, Paul S.; Maines, Mahin D.

2011-01-01

HO-2 oxidizes heme to CO and biliverdin; the latter is reduced to bilirubin by biliverdin reductase (BVR). In addition, HO-2 is a redox-sensitive K/Ca2-associated protein, and BVR is an S/T/Y kinase. The two enzymes are components of cellular defense mechanisms. This is the first reporting of regulation of HO-2 by BVR and that their coordinated increase in isolated myocytes and intact heart protects against cardiotoxicity of β-adrenergic receptor activation by isoproterenol (ISO). The induction of BVR mRNA, protein, and activity and HO-2 protein was maintained for ≥96 h; increase in HO-1 was modest and transient. In isolated cardiomyocytes, experiments with cycloheximide, proteasome inhibitor MG-132, and siBVR suggested BVR-mediated stabilization of HO-2. In both models, activation of BVR offered protection against the ligand's stimulation of apoptosis. Two human BVR-based peptides known to inhibit and activate the reductase, KKRILHC281 and KYCCSRK296, respectively, were tested in the intact heart. Perfusion of the heart with the inhibitory peptide blocked ISO-mediated BVR activation and augmented apoptosis; conversely, perfusion with the activating peptide inhibited apoptosis. At the functional level, peptide-mediated inhibition of BVR was accompanied by dysfunction of the left ventricle and decrease in HO-2 protein levels. Perfusion of the organ with the activating peptide preserved the left ventricular contractile function and was accompanied by increased levels of HO-2 protein. Finding that BVR and HO-2 levels, myocyte apoptosis, and contractile function of the heart can be modulated by small human BVR-based peptides offers a promising therapeutic approach for treatment of cardiac dysfunctions.—Ding, B., Gibbs, P. E. M., Brookes, P. S., Maines, M. D. The coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival; a reductase-based peptide counters β-adrenergic receptor ligand-mediated cardiac dysfunction. PMID:20876213

Lumican Deficiency Results In Cardiomyocyte Hypertrophy With Altered Collagen Assembly

PubMed Central

Dupuis, Loren E.; Berger, Matthew G.; Feldman, Samuel; Doucette, Lorna; Fowlkes, Vennece; Chakravarti, Shukti; Thibaudeau, Sarah; Alcala, Nicolas E.; Bradshaw, Amy D.; Kern, Christine B.

2015-01-01

The ability of the heart to adapt to increased stress is dependent on modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest LUM deficient mice (lum−/−) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum−/− hearts have not been evaluated. These studies show LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum−/− neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum−/− hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum−/− hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum−/− hearts. There was also a reduction in the β and γ forms of collagenα1(I) in lum−/− hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum−/− hearts, indicating LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease. PMID:25886697

Two-year outcome of a prospective, controlled study of a disease management programme for elderly patients with heart failure.

PubMed

Del Sindaco, Donatella; Pulignano, Giovanni; Minardi, Giovanni; Apostoli, Antonella; Guerrieri, Luca; Rotoloni, Marina; Petri, Gabriella; Fabrizi, Lino; Caroselli, Attilia; Venusti, Rita; Chiantera, Angelo; Giulivi, Alessia; Giovannini, Ezio; Leggio, Francesco

2007-05-01

Elderly heart failure patients are at high risk of events. Available studies and systematic reviews suggest that elderly patients benefit from disease management programmes (DMPs). However, important questions remain open, including the optimal follow-up intensity and duration and whether such interventions are cost-effective during long-term follow-up and in different healthcare systems. The aim of this study was to determine the long-term efficacy of a hybrid DMP in consecutive older outpatients. Intervention consisted in combined hospital-based (cardiologists and nurse-coordinators from two heart failure clinics) and home-based (patient's general practitioner visits) care. The components of the DMP were the following: discharge planning, education, therapy optimisation, improved communication, early attention to signs and symptoms. Intensive follow-up was based on scheduled hospital visits (starting within 14 days of discharge), nurse's phone call and home general practitioner visits. A group of 173 patients aged > or =70 years (mean age 77 +/- 6 years, 48% women) was randomly assigned to DMP (n = 86) or usual care (n = 87). At 2-year follow-up, a 36% reduction in all-cause death and heart failure hospital admissions was observed in DMP vs. usual care. All-cause and heart failure admissions as well as the length of hospital stay were also reduced. DMP patients reported, compared to baseline, significant improvements in functional status, quality of life and beta-blocker prescription rate. The intervention was cost-effective with a mean saving of euro 982.04 per patient enrolled. A hybrid DMP for elderly heart failure patients improves outcomes and is cost-effective over a long-term follow-up.

Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart.

PubMed

Matrone, Gianfranco; Wilson, Kathryn S; Mullins, John J; Tucker, Carl S; Denvir, Martin A

2015-06-01

Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Polarization-correlation optical microscopy of anisotropic biological layers

NASA Astrophysics Data System (ADS)

Ushenko, A. G.; Dubolazov, A. V.; Ushenko, V. A.; Ushenko, Yu. A.; Sakhnovskiy, M. Y.; Balazyuk, V. N.; Khukhlina, O.; Viligorska, K.; Bykov, A.; Doronin, A.; Meglinski, I.

2016-09-01

The theoretical background of azimuthally stable method of Jones-matrix mapping of histological sections of biopsy of myocardium tissue on the basis of spatial frequency selection of the mechanisms of linear and circular birefringence is presented. The diagnostic application of a new correlation parameter - complex degree of mutual anisotropy - is analytically substantiated. The method of measuring coordinate distributions of complex degree of mutual anisotropy with further spatial filtration of their high- and low-frequency components is developed. The interconnections of such distributions with parameters of linear and circular birefringence of myocardium tissue histological sections are found. The comparative results of measuring the coordinate distributions of complex degree of mutual anisotropy formed by fibrillar networks of myosin fibrils of myocardium tissue of different necrotic states - dead due to coronary heart disease and acute coronary insufficiency are shown. The values and ranges of change of the statistical (moments of the 1st - 4th order) parameters of complex degree of mutual anisotropy coordinate distributions are studied. The objective criteria of differentiation of cause of death are determined.

Comparison of Bystander Cardiopulmonary Resuscitation (BCPR) Performance in the Absence and Presence of Timing Devices for Coordinating Delivery of Ventilatory Breaths and Cardiac Compressions in a Model of Adult Cardiopulmonary Arrest

NASA Technical Reports Server (NTRS)

Hurst, Victor, IV; West, Sarah; Austin, Paul; Branson, Richard; Beck, George

2006-01-01

Astronaut crew medical officers (CMO) aboard the International Space Station (ISS) receive 40 hours of medical training during the 18 months preceding each mission. Part of this training ilncludes twoperson cardiopulmonary resuscitation (CPR) per training guidelines from the American Heart Association (AHA). Recent studies concluded that the use of metronomic tones improves the coordination of CPR by trained clinicians. Similar data for bystander or "trained lay people" (e.g. CMO) performance of CPR (BCPR) have been limited. The purpose of this study was to evailuate whether use of timing devices, such as audible metronomic tones, would improve BCPR perfomance by trained bystanders. Twenty pairs of bystanders trained in two-person BCPR performled BCPR for 4 minutes on a simulated cardiopulmonary arrest patient using three interventions: 1) BCPR with no timing devices, 2) BCPR plus metronomic tones for coordinating compression rate only, 3) BCPR with a timing device and metronome for coordinating ventilation and compression rates, respectively. Bystanders were evaluated on their ability to meet international and AHA CPR guidelines. Bystanders failed to provide the recommended number of breaths and number of compressions in the absence of a timing device and in the presence of audible metronomic tones for only coordinating compression rate. Bystanders using timing devices to coordinate both components of BCPR provided the reco number of breaths and were closer to providing the recommended number of compressions compared with the other interventions. Survey results indicated that bystanders preferred to use a metronome for delivery of compressions during BCPR. BCPR performance is improved by timing devices that coordinate both compressions and breaths.

Guidance signalling regulates leading edge behaviour during collective cell migration of cardiac cells in Drosophila.

PubMed

Raza, Qanber; Jacobs, J Roger

2016-11-15

Collective cell migration is the coordinated movement of cells, which organize tissues during morphogenesis, repair and some cancers. The motile cell membrane of the advancing front in collective cell migration is termed the Leading Edge. The embryonic development of the vertebrate and Drosophila hearts are both characterized by the coordinated medial migration of a bilateral cluster of mesodermal cells. In Drosophila, the cardioblasts form cohesive bilateral rows that migrate collectively as a unit towards the dorsal midline to form the dorsal vessel. We have characterized the collective cell migration of cardioblasts as an in vivo quantitative model to study the behaviour of the Leading Edge. We investigated whether guidance signalling through Slit and Netrin pathways plays a role in cell migration during heart development. Through time-lapse imaging and quantitative assessment of migratory behaviour of the cardioblasts in loss-of-function mutants, we demonstrate that both Slit and Netrin mediated signals are autonomously and concomitantly required to maximize migration velocity, filopodial and lamellipodial activities. Additionally, we show that another Slit and Netrin receptor, Dscam1, the role of which during heart development was previously unknown, is required for both normal migration of cardioblasts and luminal expansion. Leading edge behaviour analysis revealed a dosage dependent genetic interaction between Slit and Netrin receptors suggesting that downstream signalling through these receptors converge on a common output that increases leading edge activity of the cardioblasts. Finally, we found that guidance signalling maintains the balance between epithelial and mesenchymal characteristics of the migrating cardioblasts. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

NASA Technical Reports Server (NTRS)

Hayashi, Miwa; Dulchinos, Victoria

2016-01-01

Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operators mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

NASA Technical Reports Server (NTRS)

Hayashi, Miwa; Dulchinos, Victoria L.

2016-01-01

Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operator's mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

Do telemonitoring projects of heart failure fit the Chronic Care Model?

PubMed Central

Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

2014-01-01

This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. Background The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. Methods This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. Results The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. Conclusion Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future. PMID:25114664

Do telemonitoring projects of heart failure fit the Chronic Care Model?

PubMed

Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

2014-07-01

This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future.

Caveolins: targeting pro-survival signaling in the heart and brain

PubMed Central

Stary, Creed M.; Tsutsumi, Yasuo M.; Patel, Piyush M.; Head, Brian P.; Patel, Hemal H.; Roth, David M.

2012-01-01

The present review discusses intracellular signaling moieties specific to membrane lipid rafts (MLRs) and the scaffolding proteins caveolin and introduces current data promoting their potential role in the treatment of pathologies of the heart and brain. MLRs are discreet microdomains of the plasma membrane enriched in gylcosphingolipids and cholesterol that concentrate and localize signaling molecules. Caveolin proteins are necessary for the formation of MLRs, and are responsible for coordinating signaling events by scaffolding and enriching numerous signaling moieties in close proximity. Specifically in the heart and brain, caveolins are necessary for the cytoprotective phenomenon termed ischemic and anesthetic preconditioning. Targeted overexpression of caveolin in the heart and brain leads to induction of multiple pro-survival and pro-growth signaling pathways; thus, caveolins represent a potential novel therapeutic target for cardiac and neurological pathologies. PMID:23060817

Computational Cardiac Anatomy Using MRI

PubMed Central

Beg, Mirza Faisal; Helm, Patrick A.; McVeigh, Elliot; Miller, Michael I.; Winslow, Raimond L.

2005-01-01

Ventricular geometry and fiber orientation may undergo global or local remodeling in cardiac disease. However, there are as yet no mathematical and computational methods for quantifying variation of geometry and fiber orientation or the nature of their remodeling in disease. Toward this goal, a landmark and image intensity-based large deformation diffeomorphic metric mapping (LDDMM) method to transform heart geometry into common coordinates for quantification of shape and form was developed. Two automated landmark placement methods for modeling tissue deformations expected in different cardiac pathologies are presented. The transformations, computed using the combined use of landmarks and image intensities, yields high-registration accuracy of heart anatomies even in the presence of significant variation of cardiac shape and form. Once heart anatomies have been registered, properties of tissue geometry and cardiac fiber orientation in corresponding regions of different hearts may be quantified. PMID:15508155

77 FR 48985 - Notice of Meeting of the ICD-9-CM Coordination and Maintenance Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... Topics: ICD-10 Implementation Announcements Expansion of Thoracic Aorta Body Part Under Heart and Great... from thoracic aorta to abdominal aorta) ICD-10 MS-DRGs ICD-10 HAC Translations ICD-10 MCE Translations...

Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH).

PubMed

Damman, Kevin; Jaarsma, Tiny; Voors, Adriaan A; Navis, Gerjan; Hillege, Hans L; van Veldhuisen, Dirk J

2009-09-01

The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.

Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

PubMed Central

Van Leeuwen, Peter; Gustafson, Kathleen M.; Cysarz, Dirk; Geue, Daniel; May, Linda E.; Grönemeyer, Dietrich

2014-01-01

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. Methods In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. Results In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. Conclusion The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates. PMID:25162592

Aerobic exercise during pregnancy and presence of fetal-maternal heart rate synchronization.

PubMed

Van Leeuwen, Peter; Gustafson, Kathleen M; Cysarz, Dirk; Geue, Daniel; May, Linda E; Grönemeyer, Dietrich

2014-01-01

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates.

Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

EPA Science Inventory

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

Team-Based Palliative and End-of-Life Care for Heart Failure

PubMed Central

Fendler, Timothy J.; Swetz, Keith M.; Allen, Larry A.

2015-01-01

SYNOPSIS Clinical practice guidelines endorse the use of palliative care in patients with symptomatic heart failure. Palliative care is no longer seen as “giving up” or “accepting death,” but is now conceptualized as “supportive care” afforded to most patients with chronic, life-limiting illness. However, the optimal content and delivery of palliative care interventions remains unknown and its integration into existing heart failure disease management continues to be a challenge. Therefore, we will comment on the current state of multidisciplinary care for such patients, explore evidence supporting a team-based approach to palliative and end-of-life care for patients with heart failure, and identify high-priority areas for research. Ultimately, patients require a “heart failure medical home”, where various specialties may take a more central role in coordination of patient care at different times in the disease span, sometimes transitioning leadership from primary care to cardiology to palliative care. PMID:26142643

Comparison of organs' shapes with geometric and Zernike 3D moments.

PubMed

Broggio, D; Moignier, A; Ben Brahim, K; Gardumi, A; Grandgirard, N; Pierrat, N; Chea, M; Derreumaux, S; Desbrée, A; Boisserie, G; Aubert, B; Mazeron, J-J; Franck, D

2013-09-01

The morphological similarity of organs is studied with feature vectors based on geometric and Zernike 3D moments. It is particularly investigated if outliers and average models can be identified. For this purpose, the relative proximity to the mean feature vector is defined, principal coordinate and clustering analyses are also performed. To study the consistency and usefulness of this approach, 17 livers and 76 hearts voxel models from several sources are considered. In the liver case, models with similar morphological feature are identified. For the limited amount of studied cases, the liver of the ICRP male voxel model is identified as a better surrogate than the female one. For hearts, the clustering analysis shows that three heart shapes represent about 80% of the morphological variations. The relative proximity and clustering analysis rather consistently identify outliers and average models. For the two cases, identification of outliers and surrogate of average models is rather robust. However, deeper classification of morphological feature is subject to caution and can only be performed after cross analysis of at least two kinds of feature vectors. Finally, the Zernike moments contain all the information needed to re-construct the studied objects and thus appear as a promising tool to derive statistical organ shapes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A critical pathway for the frail elderly cardiac patient.

PubMed

Wit, Mirjam; Schaap, Annet; Umans, Victor

2011-12-01

The medical community needs to better respond to the predictable complexities associated with admission of frail and elderly cardiac patients who may need specific attention and care programs. The nurse practitioner can play an important role to continue and coordinate nursing and medical care. We propose a new critical pathway designed to improve cardiac and nursing care for frail elderly cardiac patients admitted with heart failure or atrial fibrillation. The critical pathway is developed by the nurse practitioner who will act as a pathway coordinator and take care of the medical care of these patients in a teaching hospital setting. This critical pathway is applied to all patients aged >75 years who are admitted for heart failure or atrial fibrillation. The pathway implementation identified 5 important socio-medical parameters that may account for a delayed length of stay, even in patients without a complicated medical situation: delirium and fall prevention, nutritional awareness, fluid restriction efforts, and information optimization of patients and spouses. We developed a critical care pathway for the frail elderly patients who are admitted for heart failure or atrial fibrillation. In doing so, we have been able to change the medical and social management of these patients at a general cardiology ward in a teaching hospital.

Building a comprehensive team for the longitudinal care of single ventricle heart defects: Building blocks and initial results.

PubMed

Texter, Karen; Davis, Jo Ann M; Phelps, Christina; Cheatham, Sharon; Cheatham, John; Galantowicz, Mark; Feltes, Timothy F

2017-07-01

With increasing survival of children with HLHS and other single ventricle lesions, the complexity of medical care for these patients is substantial. Establishing and adhering to best practice models may improve outcome, but requires careful coordination and monitoring. In 2013 our Heart Center began a process to build a comprehensive Single Ventricle Team designed to target these difficult issues. Comprehensive Single Ventricle Team in 2014 was begun, to standardize care for children with single ventricle heart defects from diagnosis to adulthood within our institution. The team is a multidisciplinary group of providers committed to improving outcomes and quality of life for children with single ventricle heart defects, all functioning within the medical home of our heart center. Standards of care were developed and implemented in five target areas to standardize medical management and patient and family support. Under the team 100 patients have been cared for. Since 2014 a decrease in interstage mortality for HLHS were seen. Using a team approach and the tools of Quality Improvement they have been successful in reaching high protocol compliance for each of these areas. This article describes the process of building a successful Single Ventricle team, our initial results, and lessons learned. Additional study is ongoing to demonstrate the effects of these interventions on patient outcomes. © 2017 Wiley Periodicals, Inc.

European homograft bank: twenty years of cardiovascular tissue banking and collaboration with transplant coordination in Europe.

PubMed

Jashari, R; Goffin, Y; Vanderkelen, A; Van Hoeck, B; du Verger, A; Fan, Y; Holovska, V; Brahy, O

2010-01-01

Established in 1989 in Brussels as an international nonprofit association, the European Homograft Bank (EHB) has been collaborating closely with the transplant coordination of the different centers in Belgium and other European countries. Donor selection is made after discussion of exclusion criteria with the transplant coordinator of the procurement center. EHB collaborates with 15 Belgian, 11 German, 10 French, 10 Swiss, 3 Italian, 3 Dutch, and some other procurement and/or implantation centers. Donor ages range from newborn to 65 years. Tissue preparation, morphologic evaluation, and functional testing are performed under Class A laminar flow. After decontamination in a cocktail of 3 antibiotics (lincomycin, vancomycin, and polymixin B) during 20-48 hours, the tissues cryopreserved with liquid nitrogen to -100 degrees C are stored in vapors of liquid nitrogen below -150 degrees C for a maximum of 5 years. Systematic virologic examination of donor blood is performed for HIV, HTLV, hepatitis B/C, and syphilis, as well as for enteroviruses, Q fever, malaria, and West Nile virus by indication. Bacteriologic examination for anaerobic and aerobic contamination is performed at the different steps of processing. Histologic examination for malignant disease and infection is performed systematically. Indications for implantation are discussed with the requesting surgeon. Transport to the implantation center is carried out safely in a dry shipper at -150 degrees C or in dry ice at -76 degrees C. The EHB received 4,511 hearts and 1,169 batches of arteries from January 1989 to December 2008. The 5,133 heart valves (1,974 aortic, 3,106 pulmonary, and 53 mitral) and 2,066 arterial segments have been prepared and stored; 4,600 cryopreserved valvular (2,717 pulmonary, 1,835 aortic, and 48 mitral) and 1,937 arterial allografts have been distributed for implantation in various European Cardiovascular Centers. EHB is not always able to meet the increased demand for heart valves and arterial allografts. Collaboration between the EHB and the Transplant Coordination is satisfactory. Donor selection criteria are discussed with the transplant coordinator; whereas, implantation indication, with the implanting surgeon. Because the EHB is not always able to meet demands for the cryopreserved valves and arterial segments, there is a need to increase number of procurements. Cardiovascular surgeons need to play more active roles in the resolution of this problem.

Putting it altogether: improving performance in heart failure outcomes, part 2.

PubMed

Clancy, Thomas R

2009-09-01

As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on management in social organizations such as hospitals. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This is the 10th in a series of articles applying complex systems science to the traditional management concepts of planning, organizing, directing, coordinating, and controlling. As follow-up to the case study in this column's June 2009 article, this article highlights the interventions and outcomes of the study.

Remote Measurements of Heart and Respiration Rates for Telemedicine

PubMed Central

Qian, Yi; Tsien, Joe Z.

2013-01-01

Non-contact and low-cost measurements of heart and respiration rates are highly desirable for telemedicine. Here, we describe a novel technique to extract blood volume pulse and respiratory wave from a single channel images captured by a video camera for both day and night conditions. The principle of our technique is to uncover the temporal dynamics of heart beat and breathing rate through delay-coordinate transformation and independent component analysis-based deconstruction of the single channel images. Our method further achieves robust elimination of false positives via applying ratio-variation probability distributions filtering approaches. Moreover, it enables a much needed low-cost means for preventing sudden infant death syndrome in new born infants and detecting stroke and heart attack in elderly population in home environments. This noncontact-based method can also be applied to a variety of animal model organisms for biomedical research. PMID:24115996

Assessing Cardiac Metabolism: A Scientific Statement From the American Heart Association.

PubMed

Taegtmeyer, Heinrich; Young, Martin E; Lopaschuk, Gary D; Abel, E Dale; Brunengraber, Henri; Darley-Usmar, Victor; Des Rosiers, Christine; Gerszten, Robert; Glatz, Jan F; Griffin, Julian L; Gropler, Robert J; Holzhuetter, Hermann-Georg; Kizer, Jorge R; Lewandowski, E Douglas; Malloy, Craig R; Neubauer, Stefan; Peterson, Linda R; Portman, Michael A; Recchia, Fabio A; Van Eyk, Jennifer E; Wang, Thomas J

2016-05-13

In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart's needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on "Assessing Cardiac Metabolism" seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity. © 2016 American Heart Association, Inc.

Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Thompson, B Gregory; Brown, Robert D; Amin-Hanjani, Sepideh; Broderick, Joseph P; Cockroft, Kevin M; Connolly, E Sander; Duckwiler, Gary R; Harris, Catherine C; Howard, Virginia J; Johnston, S Claiborne Clay; Meyers, Philip M; Molyneux, Andrew; Ogilvy, Christopher S; Ringer, Andrew J; Torner, James

2015-08-01

The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment. © 2015 American Heart Association, Inc.

Registered Nurses’ Perceptions about the Situation of Family Caregivers to Patients with Heart Failure - A Focus Group Interview Study

PubMed Central

2016-01-01

Introduction Heart failure is a growing public health problem associated with poor quality of life and significant morbidity and mortality. The majority of heart failure care is provided by family caregivers, and is associated with caregiver burden and reduced quality of life. Research emphasizes that future nursing interventions should recognize the importance of involving family caregivers to achieve optimal outcomes. Aims The aims of this study are to explore registered nurses’ perceptions about the situation of family caregivers to patients with heart failure, and registered nurses’ interventions, in order to improve family caregivers’ situation. Methods The study has a qualitative design with an inductive approach. Six focus group interviews were held with 23 registered nurses in three hospitals and three primary health care centres. Data were analysed using qualitative content analysis. Results Two content areas were identified by the a priori study aims. Four categories and nine sub-categories emerged in the analysis process. The content area “Family caregivers' situation” includes two categories: “To be unburdened” and “To comprehend the heart failure condition and its consequences”. The content area “Interventions to improve family caregivers' situation” includes two categories: “Individualized support and information” and “Bridging contact”. Conclusions Registered nurses perceive family caregivers' situation as burdensome, characterized by worry and uncertainty. In the PHCCs, the continuity and security of an RN as a permanent health care contact was considered an important and sustainable intervention to better care for family caregivers' worry and uncertainty. In the nurse-led heart failure clinics in hospitals, registered nurses can provide family caregivers with the opportunity of involvement in their relative's health care and address congruence and relationship quality within the family through the use of "Shared care" and or Family-centred care. Registered nurses consider it necessary to have a coordinated individual care plan as a basis for collaboration between the county council and the municipality. PMID:27505287

Registered Nurses' Perceptions about the Situation of Family Caregivers to Patients with Heart Failure - A Focus Group Interview Study.

PubMed

Gusdal, Annelie K; Josefsson, Karin; Thors Adolfsson, Eva; Martin, Lene

2016-01-01

Heart failure is a growing public health problem associated with poor quality of life and significant morbidity and mortality. The majority of heart failure care is provided by family caregivers, and is associated with caregiver burden and reduced quality of life. Research emphasizes that future nursing interventions should recognize the importance of involving family caregivers to achieve optimal outcomes. The aims of this study are to explore registered nurses' perceptions about the situation of family caregivers to patients with heart failure, and registered nurses' interventions, in order to improve family caregivers' situation. The study has a qualitative design with an inductive approach. Six focus group interviews were held with 23 registered nurses in three hospitals and three primary health care centres. Data were analysed using qualitative content analysis. Two content areas were identified by the a priori study aims. Four categories and nine sub-categories emerged in the analysis process. The content area "Family caregivers' situation" includes two categories: "To be unburdened" and "To comprehend the heart failure condition and its consequences". The content area "Interventions to improve family caregivers' situation" includes two categories: "Individualized support and information" and "Bridging contact". Registered nurses perceive family caregivers' situation as burdensome, characterized by worry and uncertainty. In the PHCCs, the continuity and security of an RN as a permanent health care contact was considered an important and sustainable intervention to better care for family caregivers' worry and uncertainty. In the nurse-led heart failure clinics in hospitals, registered nurses can provide family caregivers with the opportunity of involvement in their relative's health care and address congruence and relationship quality within the family through the use of "Shared care" and or Family-centred care. Registered nurses consider it necessary to have a coordinated individual care plan as a basis for collaboration between the county council and the municipality.

Telerehabilitation for OIF/OEF Returnees with Combat-Related Traumatic Brain Injury

DTIC Science & Technology

2013-06-01

VA has no national program for providing individualized care coordination for veterans via telemedicine. It does have an e-health portal where...Heart Failure, diabetes, hypertension , COPD and mental illness. However, this technology does not allow for the posting of individualized questions

Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

PubMed

Luna-Zurita, Luis; Stirnimann, Christian U; Glatt, Sebastian; Kaynak, Bogac L; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K; Pollard, Katherine S; Müller, Christoph W; Bruneau, Benoit G

2016-02-25

Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Output variability across animals and levels in a motor system

PubMed Central

Norris, Brian J; Günay, Cengiz; Kueh, Daniel

2018-01-01

Rhythmic behaviors vary across individuals. We investigated the sources of this output variability across a motor system, from the central pattern generator (CPG) to the motor plant. In the bilaterally symmetric leech heartbeat system, the CPG orchestrates two coordinations in the bilateral hearts with different intersegmental phase relations (Δϕ) and periodic side-to-side switches. Population variability is large. We show that the system is precise within a coordination, that differences in repetitions of a coordination contribute little to population output variability, but that differences between bilaterally homologous cells may contribute to some of this variability. Nevertheless, much output variability is likely associated with genetic and life history differences among individuals. Variability of Δϕ were coordination-specific: similar at all levels in one, but significantly lower for the motor pattern than the CPG pattern in the other. Mechanisms that transform CPG output to motor neurons may limit output variability in the motor pattern. PMID:29345614

Regaining legitimacy in the context of global governance? UNESCO, Education for All coordination and the Global Monitoring Report

NASA Astrophysics Data System (ADS)

Edwards, D. Brent; Okitsu, Taeko; da Costa, Romina; Kitamura, Yuto

2017-06-01

This research note shares insights which resulted from a larger study into the ways in which the United Nations Educational, Scientific and Cultural Organization (UNESCO) - during 2010-2014 - used its position as coordinator of the post-Dakar Framework for Action (initiated at the World Education Forum held in 2000 and designed to reinvigorate the Education for All initiative) to help it regain some of the legitimacy it had lost in the preceding decades. The research study focused on the role of both the UNESCO Education for All Follow-up Unit and the production of the Global Monitoring Report (GMR) during the 2000s because they were at the heart of UNESCO's efforts to repair its image and renew its impact in one area of global governance, specifically in the global education policy field. The study's findings were based on an analysis of documents, archives and interviews ( n = 17) with key actors inside and outside UNESCO, including representatives of UNESCO's peer institutions.

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. Methods/Design A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain). All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. Discussion A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Trial Registration Australian New Zealand Clinical Trial Registry 12609000437268 PMID:21366927

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial.

PubMed

Du, Hui Y; Newton, Phillip J; Zecchin, Robert; Denniss, Robert; Salamonson, Yenna; Everett, Bronwyn; Currow, David C; Macdonald, Peter S; Davidson, Patricia M

2011-03-02

Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain).All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Australian New Zealand Clinical Trial Registry 12609000437268.

Hearts and minds: Coordination of neurocognitive and cardiovascular regulation in children and adolescents.

PubMed

Chapman, H A; Woltering, S; Lamm, C; Lewis, M D

2010-05-01

Emotional reactions involve changes in both cognitive and bodily processes. Therefore, effective emotion regulation may also involve modulation of responses in both of these systems. The present study investigated the relationship between regulation of cognition and regulation of the heart in children and adolescents, using a go/nogo task in combination with the induction of negative emotions. Behavioral, temperamental and event-related brain potential (ERP) indicators of inhibitory cognitive control were collected, as was a measure of parasympathetic control of the heart (respiratory sinus arrhythmia, RSA). Independently of age, RSA was correlated with nogo N2 magnitudes during the emotion-induction procedure. RSA during the task was also correlated with N2 latencies and with behavioral accuracy before, during and after the emotion induction. Resting RSA was correlated with individual differences in the capacity for effortful cognitive control, as measured by questionnaire. These results suggest that emotional responses in seemingly distinct neurophysiological systems may be regulated in an integrated fashion throughout the developmental span tested. Copyright 2010 Elsevier B.V. All rights reserved.

Experiences and preferences of care among Swedish immigrants following a prenatal diagnosis of congenital heart defect in the fetus: a qualitative interview study.

PubMed

Carlsson, Tommy; Marttala, Ulla Melander; Mattsson, Elisabet; Ringnér, Anders

2016-06-02

Immigrants experience significant challenges when in contact with healthcare and report less satisfaction with maternity care compared to native Swedes. Research that gives voice to pregnant immigrant women and their partners following a prenatal diagnosis of a fetal anomaly is scarce. Thus, the aim of this study was to explore experiences and preferences of care following a prenatal diagnosis of congenital heart defect among Swedish immigrants. Pregnant immigrants and their partners were consecutively recruited following a prenatal diagnosis of a congenital heart defect in the fetus. Nine respondents were interviewed in five interviews, four with the aid of a professional interpreter. The material was analyzed using manifest qualitative content analysis. The analysis resulted in five categories: 1) "Trustworthy information", 2) "Language barriers", 3) "Psychosocial situation", 4) "Peer support", and 5) "Religious positions". The potential need for interpreter services, visual information, psychosocial support, coordination with welfare officers, and respect for religious positions about termination of pregnancy are all important aspects for health professionals to consider when consulting immigrants faced with a prenatal diagnosis of fetal anomaly in the fetus. Peer support within this context needs to be further explored in future studies.

Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Winstein, Carolee J; Stein, Joel; Arena, Ross; Bates, Barbara; Cherney, Leora R; Cramer, Steven C; Deruyter, Frank; Eng, Janice J; Fisher, Beth; Harvey, Richard L; Lang, Catherine E; MacKay-Lyons, Marilyn; Ottenbacher, Kenneth J; Pugh, Sue; Reeves, Mathew J; Richards, Lorie G; Stiers, William; Zorowitz, Richard D

2016-06-01

The aim of this guideline is to provide a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council's Scientific Statement Oversight Committee and the AHA's Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through 2014. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal and external peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. Stroke rehabilitation requires a sustained and coordinated effort from a large team, including the patient and his or her goals, family and friends, other caregivers (eg, personal care attendants), physicians, nurses, physical and occupational therapists, speech-language pathologists, recreation therapists, psychologists, nutritionists, social workers, and others. Communication and coordination among these team members are paramount in maximizing the effectiveness and efficiency of rehabilitation and underlie this entire guideline. Without communication and coordination, isolated efforts to rehabilitate the stroke survivor are unlikely to achieve their full potential. As systems of care evolve in response to healthcare reform efforts, postacute care and rehabilitation are often considered a costly area of care to be trimmed but without recognition of their clinical impact and ability to reduce the risk of downstream medical morbidity resulting from immobility, depression, loss of autonomy, and reduced functional independence. The provision of comprehensive rehabilitation programs with adequate resources, dose, and duration is an essential aspect of stroke care and should be a priority in these redesign efforts. (Stroke.2016;47:e98-e169. DOI: 10.1161/STR.0000000000000098.). © 2016 American Heart Association, Inc.

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

PubMed

Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

2016-10-01

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

Methods and means of Fourier-Stokes polarimetry and the spatial frequency filtering of phase anisotropy manifestations

NASA Astrophysics Data System (ADS)

Novakovskaya, O. Yu.; Ushenko, A. G.; Dubolazov, A. V.; Ushenko, V. A.; Ushenko, Yu. A.; Sakhnovskiy, M. Yu.; Soltys, I. V.; Zhytaryuk, V. H.; Olar, O. V.; Sidor, M.; Gorsky, M. P.

2016-12-01

The theoretical background of azimuthally stable method of Jones-matrix mapping of histological sections of biopsy of myocardium tissue on the basis of spatial frequency selection of the mechanisms of linear and circular birefringence is presented. The diagnostic application of a new correlation parameter - complex degree of mutual anisotropy - is analytically substantiated. The method of measuring coordinate distributions of complex degree of mutual anisotropy with further spatial filtration of their high- and low-frequency components is developed. The interconnections of such distributions with parameters of linear and circular birefringence of myocardium tissue histological sections are found. The comparative results of measuring the coordinate distributions of complex degree of mutual anisotropy formed by fibrillar networks of myosin fibrils of myocardium tissue of different necrotic states - dead due to coronary heart disease and acute coronary insufficiency are shown. The values and ranges of change of the statistical (moments of the 1st - 4th order) parameters of complex degree of mutual anisotropy coordinate distributions are studied. The objective criteria of differentiation of cause of death are determined.

Correlations of psycho-physiological parameters influencing the physical fitness of aged women.

PubMed

Bretz, É; Kóbor-Nyakas, D É; Bretz, K J; Hrehuss, N; Radák, Z; Nyakas, Csaba

2014-12-01

Regular assessment of psycho-physiological parameters in aged subjects helps to clarify physical and mental conditions which are important in the prevention of health-endangering events to assure a healthy aging. Thirty older care female residents consented voluntarily to participate in the study. The somatic and psycho-physiological parameters recorded were handgrip force, disjunctive reaction time, balance control and whole body movement coordination, the electrocardiogram and heart rate variability. Significant correlations were found between (a) reaction time and balance control efficiency (r = -0.567, p < 0.009), (b) reaction time and movement coordination accuracy (r = -0.453, p < 0.045), (c) cardiac state and movement coordination accuracy (r = 0.545, p < 0.016), (d) cardiac stress and cardiac state (r = -0.495, p < 0.031), and (e) cardiac stress and force (r = -0.822, p < 0.045). In conclusion, for the aim of establishing basic battery tests for assessing psycho-physiological condition of physical fitness our results emphasize the importance of systematic physical activity, endurance and strength training supporting muscle force, balance control and whole-body movement coordination, in addition to improving the cardiac stress index level. The strong interrelation among these parameters allows the drawing of a more complete view regarding the health condition of aged individuals.

76 FR 61722 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... Institute Special Emphasis Panel, Data Coordinating Center for the Cardiovascular Cell Therapy Research... Special Emphasis Panel, Regional Clinical Center for the Cardiovascular Cell Therapy Research Network... Capture Agents for Cardiovascular Research. Date: October 24, 2011. Time: 1 p.m. to 3 p.m. Agenda: To...

Telerehabilitation for OIF/OEF Returnees with Combat-Related Traumatic Brain Injury

DTIC Science & Technology

2012-06-01

coordination for veterans via telemedicine. It does have an e-health portal where veterans may submit and track vital signs such as BP readings and...of its program to support patients with chronic conditions such as Congestive Heart Failure, diabetes, hypertension , COPD and mental illness. However

78 FR 52921 - Office of the National Coordinator for Health Information Technology; Announcement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

... higher for patients with chronic conditions such as diabetes, asthma, and heart conditions \\3\\ and failure to treat both physical and mental health conditions results in poorer health outcomes and higher... third party claims for damages arising from or related to competition activities. Registration Process...

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it; Ciaccio, Chiara; Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, I-70126 Bari

2011-01-07

Research highlights: {yields} Cardiolipin binding to cytochrome c. {yields} Cardiolipin-dependent peroxynitrite isomerization by cytochrome c. {yields} Cardiolipin-cytochrome c complex plays pro-apoptotic effects. {yields} Cardiolipin-cytochrome c complex plays anti-apoptotic effects. -- Abstract: Upon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does notmore » catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CL-cytc-Fe(III)-mediated isomerization of peroxynitrite (k{sub on}) is (3.2 {+-} 0.4) x 10{sup 5} M{sup -1} s{sup -1}. The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1 {+-} 0.8) x 10{sup -5} M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.« less

From Adult Finger Tapping to Fetal Heart Beating: Retracing the Role of Coordination in Constituting Agency.

PubMed

Solfo, Alessandro; van Leeuwen, Cees

2018-01-01

Sense of agency can be defined as the self-awareness of bodily movement, whereas extended agency as the self-awareness of affecting, through movement, events concomitant with movement. As a distinctive manifestation of agency, we review Spizzo's effect. This effect arises when agents coordinate their rhythmic movements with visual pulses. Once coordination is established, agents feel controlling the onset or the offset of the pulses through their movements. Spizzo's effect, therefore, constitutes a manifest case of extended agency, in which agents are aware of controlling, through movement, the pulses temporally concomitant with movement. We propose that sense of agency requires continuity of kinesthesia, which in turn requires the continuity of selfhood. The continuity of kinesthesia is necessarily deduced from the consistent kinematics observed in movements, whereas the continuity of selfhood may stem from the patterns of rhythmic coordination that humans encounter ever since intrauterine life. The primacy of these patterns in adults is in accordance with phenomena such as Spizzo's effect, which require coordination to be induced. We, therefore, propose coordination as the fundamental interaction from which selfhood, kinesthesia, and agency arise. Copyright © 2017 Cognitive Science Society, Inc.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

PubMed

Gelb, Bruce; Brueckner, Martina; Chung, Wendy; Goldmuntz, Elizabeth; Kaltman, Jonathan; Kaski, Juan Pablo; Kim, Richard; Kline, Jennie; Mercer-Rosa, Laura; Porter, George; Roberts, Amy; Rosenberg, Ellen; Seiden, Howard; Seidman, Christine; Sleeper, Lynn; Tennstedt, Sharon; Kaltman, Jonathan; Schramm, Charlene; Burns, Kristin; Pearson, Gail; Rosenberg, Ellen

2013-02-15

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.

The day/night proteome in the murine heart.

PubMed

Podobed, Peter; Pyle, W Glen; Ackloo, Suzanne; Alibhai, Faisal J; Tsimakouridze, Elena V; Ratcliffe, William F; Mackay, Allison; Simpson, Jeremy; Wright, David C; Kirby, Gordon M; Young, Martin E; Martino, Tami A

2014-07-15

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.

The Congenital Heart Disease Genetic Network Study

PubMed Central

2013-01-01

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome. PMID:23410879

The day/night proteome in the murine heart

PubMed Central

Podobed, Peter; Pyle, W. Glen; Ackloo, Suzanne; Alibhai, Faisal J.; Tsimakouridze, Elena V.; Ratcliffe, William F.; Mackay, Allison; Simpson, Jeremy; Wright, David C.; Kirby, Gordon M.; Young, Martin E.

2014-01-01

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function. PMID:24789993

Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis.

PubMed

Vaiyapuri, Sakthivel; Flora, Gagan D; Gibbins, Jonathan M

2015-06-01

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischaemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a co-ordinated manner to prevent loss of blood and control wound repair. Previous report (1) indicates that the stability and functions of a thrombus are maintained through sustained, contact-dependent signalling between platelets. Given the role of gap junctions in the co-ordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

Pilot study of an Internet patient-physician communication tool for heart failure disease management.

PubMed

Wu, Robert C; Delgado, Diego; Costigan, Jeannine; Ross, Heather; MacIver, Jane

2006-01-01

Internet disease management has the promise of improving care in patients with heart failure but evidence supporting its use is limited. We have designed a Heart Failure Internet Communication Tool (HFICT), allowing patients to enter messages for clinicians, as well as their daily symptoms, weight, blood pressure and heart rate. Clinicians review the information on the same day and provide feedback. This pilot study evaluated the feasibility and patients' acceptability of using the Internet to communicate with patients with symptomatic heart failure. Patients with symptomatic heart failure were instructed how to use the Internet communication tool. The primary outcome measure was the proportion of patients who used the system regularly by entering information on average at least once per week for at least 3 months. Secondary outcomes measures included safety and maintainability of the tool. We also conducted a content analysis of a subset of the patient and clinician messages entered into the comments field. Between 3 May 1999 and 1 November 2002, 62 patients (mean age 48.7 years) were enrolled. At 3 months 58 patients were alive and without a heart transplant. Of those, 26 patients (45%; 95% Confidence Interval, 0.33-0.58) continued using the system at 3 months. In 97% of all entries by participants weight was included; 68% of entries included blood pressure; and 71% of entries included heart rate. In 3,386 entries out of all 5,098 patient entries (66%), comments were entered. Functions that were not used included the tracking of diuretics, medications and treatment goals. The tool appeared to be safe and maintainable. Workload estimates for clinicians for entering a response to each patient's entry ranged from less than a minute to 5 minutes or longer for a detailed response. Patients sent 3,386 comments to the Heart Function Clinic. Based on the content analysis of 100 patient entries, the following major categories of communication were identified: patient information; patient symptoms; patient questions regarding their condition; patient coordinating own care; social responses. The number of comments decreased over time for both patients and clinicians. While the majority of patients discontinued use, 45% of the patients used the system and continued to use it on average for 1.5 years. An Internet tool is a feasible method of communication in a substantial proportion of patients with heart failure. Further study is required to determine whether clinical outcomes, such as quality of life or frequency of hospitalization, are improved.

Using complexity metrics with R-R intervals and BPM heart rate measures.

PubMed

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics-fractal (DFA) and recurrence (RQA) analyses-reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, "oversampled" BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics.

Using complexity metrics with R-R intervals and BPM heart rate measures

PubMed Central

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics—fractal (DFA) and recurrence (RQA) analyses—reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, “oversampled” BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics. PMID:23964244

Effectiveness and Factors Determining the Success of Management Programs for Patients With Heart Failure: A Systematic Review and Meta-analysis.

PubMed

Oyanguren, Juana; Latorre García, Pedro María; Torcal Laguna, Jesús; Lekuona Goya, Iñaki; Rubio Martín, Susana; Maull Lafuente, Elena; Grandes, Gonzalo

2016-10-01

Heart failure management programs reduce hospitalizations. Some studies also show reduced mortality. The determinants of program success are unknown. The aim of the present study was to update our understanding of the reductions in mortality and readmissions produced by these programs, elucidate their components, and identify the factors determining program success. Systematic literature review (1990-2014; PubMed, EMBASE, CINAHL, Cochrane Library) and manual search of relevant journals. The studies were selected by 3 independent reviewers. Methodological quality was evaluated in a blinded manner by an external researcher (Jadad scale). These results were pooled using random effects models. Heterogeneity was evaluated with the I 2 statistic, and its explanatory factors were determined using metaregression analysis. Of the 3914 studies identified, 66 randomized controlled clinical trials were selected (18 countries, 13 535 patients). We determined the relative risks to be 0.88 for death (95% confidence interval [95%CI], 0.81-0.96; P < .002; I 2 , 6.1%), 0.92 for all-cause readmissions (95%CI, 0.86-0.98; P < .011; I 2 , 58.7%), and 0.80 for heart failure readmissions (95%CI, 0.71-0.90; P < .0001; I 2 , 52.7%). Factors associated with program success were implementation after 2001, program location outside the United States, greater baseline use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, a higher number of intervention team members and components, specialized heart failure cardiologists and nurses, protocol-driven education and its assessment, self-monitoring of signs and symptoms, detection of deterioration, flexible diuretic regimen, early care-seeking among patients and prompt health care response, psychosocial intervention, professional coordination, and program duration. We confirm the reductions in mortality and readmissions with heart failure management programs. Their success is associated with various structural and intervention variables. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.

PubMed

Trembley, Michael A; Quijada, Pearl; Agullo-Pascual, Esperanza; Tylock, Kevin M; Colpan, Mert; Dirkx, Ronald A; Myers, Jason R; Mickelsen, Deanne M; de Mesy Bentley, Karen; Rothenberg, Eli; Moravec, Christine S; Alexis, Jeffrey D; Gregorio, Carol C; Dirksen, Robert T; Delmar, Mario; Small, Eric M

2018-05-01

Background -Hypertrophic cardiomyocyte (CM) growth and dysfunction accompanies various forms of heart disease. The mechanisms responsible for transcriptional changes that impact cardiac physiology and the transition to heart failure (HF) are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling CM electrical activity and force transmission, and is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy. Methods -Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy (SMLM) were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor-A (MRTF-A) and -B specifically in adult CMs to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling. Results -We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure (HF). Although mice lacking MRTFs in adult CMs display normal cardiac physiology at baseline, pressure overload leads to rapid HF characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and CM adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by SMLM may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target. Conclusions -Taken together, our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates crosstalk between the actin and microtubule cytoskeleton and maintains ID integrity and CM homeostasis in heart disease.

Implementation of Policy, Systems, and Environmental Community-Based Interventions for Cardiovascular Health Through a National Not-for-Profit: A Multiple Case Study.

PubMed

Garney, Whitney R; Szucs, Leigh E; Primm, Kristin; King Hahn, Laura; Garcia, Kristen M; Martin, Emily; McLeroy, Kenneth

2018-05-01

In 2014, the Centers for Disease Control and Prevention funded the American Heart Association to implement policy, systems, and environment-focused strategies targeting access to healthy food and beverages, physical activity, and smoke-free environments. To understand factors affecting implementation and variations in success across sites, evaluators conducted a multiple case study. Based on past literature, community sites were categorized as capacity-building or implementation-ready, for comparison. A sample of six communities were selected using a systematic selection tool. Through site visits, evaluators conducted interviews with program staff and community partners and assessed action plans. Evaluators identified important implications for nationally coordinated community-based prevention programming. Differences in implementation varied by the communities' readiness, with the most notable differences in how they planned activities and defined success. Existing partner relationships (or lack thereof) played a significant role, regardless of the American Heart Association's existing presence within the communities, in the progression of initiatives and the differences observed among phases. Last, goals in capacity-building sites were tied to organizational goals while goals in implementation-ready sites were more incremental with increased community influence and buy-in. Using national organizations as a mechanism to carry out large-scale community-based prevention work is a viable option that provides coordinated, wide-scale implementation without sacrificing a community's priorities or input. In funding future initiatives, the presence of relationships and the time needed to cultivate such relationships should be accounted for in the planning and implementation processes, as well as both local and national expectations.

Model for heart failure education.

PubMed

Baldonado, Analiza; Dutra, Danette; Abriam-Yago, Katherine

2014-01-01

Heart failure (HF) is the heart's inability to meet the body's need for blood and oxygen. According to the American Heart Association 2013 update, approximately 5.1 million people are diagnosed with HF in the United States in 2006. Heart failure is the most common diagnosis for hospitalization. In the United States, the HF direct and indirect costs are estimated to be US $39.2 billion in 2010. To address this issue, nursing educators designed innovative teaching frameworks on HF management both in academia and in clinical settings. The model was based on 2 resources: the American Association of Heart Failure Nurses (2012) national nursing certification and the award-winning Pierce County Responsive Care Coordination Program. The HF educational program is divided into 4 modules. The initial modules offer foundational levels of Bloom's Taxonomy then progress to incorporate higher-levels of learning when modules 3 and 4 are reached. The applicability of the key components within each module allows formatting to enhance learning in all areas of nursing, from the emergency department to intensive care units to the medical-surgical step-down units. Also applicable would be to provide specific aspects of the modules to nurses who care for HF patients in skilled nursing facility, rehabilitation centers, and in the home-health care setting.

Cardiomyocyte Ogt limits ventricular dysfunction in mice following pressure overload without affecting hypertrophy.

PubMed

Dassanayaka, Sujith; Brainard, Robert E; Watson, Lewis J; Long, Bethany W; Brittian, Kenneth R; DeMartino, Angelica M; Aird, Allison L; Gumpert, Anna M; Audam, Timothy N; Kilfoil, Peter J; Muthusamy, Senthilkumar; Hamid, Tariq; Prabhu, Sumanth D; Jones, Steven P

2017-05-01

The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure. Protein O-GlcNAcylation levels were increased in myocardial tissue from heart failure patients compared with normal patients. To test the role of OGT in the heart, we subjected cardiomyocyte-specific, inducibly deficient Ogt (i-cmOgt -/- ) mice and Ogt competent littermate wild-type (WT) mice to transverse aortic constriction. Deletion of cardiomyocyte Ogt significantly decreased O-GlcNAcylation and exacerbated ventricular dysfunction, without producing widespread changes in metabolic transcripts. Although some changes in hypertrophic and fibrotic signaling were noted, there were no histological differences in hypertrophy or fibrosis. We next determined whether significant differences were present in i-cmOgt -/- cardiomyocytes from surgically naïve mice. Interestingly, markers of cardiomyocyte dedifferentiation were elevated in Ogt-deficient cardiomyocytes. Although no significant differences in cardiac dysfunction were apparent after recombination, it is possible that such changes in dedifferentiation markers could reflect a larger phenotypic shift within the Ogt-deficient cardiomyocytes. We conclude that cardiomyocyte Ogt is not required for cardiomyocyte hypertrophy in vivo; however, loss of Ogt may exert subtle phenotypic differences in cardiomyocytes that sensitize the heart to pressure overload-induced ventricular dysfunction.

Medical Device Plug-and-Play Interoperability Standards and Technology Leadership

DTIC Science & Technology

2015-10-01

implemented connectivity to an EHR as an HL7 FHIR gateway from OpenICE. The monitor we used can measure heart rate from EKG, from the pulse oximeter , or... Pulse 2014:5(6):37-39. 2. Wu PL, Raguraman D, Sha L, Berlin RB, Goldman JM. WiP abstract: A treatment coordination protocol for cyber-physical-human

75 FR 19983 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... Cardiovascular Conditions (GenTAC). Date: May 12, 2010. Time: 10 a.m. to 1 p.m. Agenda: To review and evaluate... Emphasis Panel, NHLBI Cardiovascular Outcomes Research Coordinating Unit. Date: May 25, 2010. Time: 8 a.m... Blood Institute Special Emphasis Panel, NHLBI Centers for Cardiovascular Outcomes Research. Date: May 25...

Design of an omnidirectional single-point photodetector for large-scale spatial coordinate measurement

NASA Astrophysics Data System (ADS)

Xie, Hongbo; Mao, Chensheng; Ren, Yongjie; Zhu, Jigui; Wang, Chao; Yang, Lei

2017-10-01

In high precision and large-scale coordinate measurement, one commonly used approach to determine the coordinate of a target point is utilizing the spatial trigonometric relationships between multiple laser transmitter stations and the target point. A light receiving device at the target point is the key element in large-scale coordinate measurement systems. To ensure high-resolution and highly sensitive spatial coordinate measurement, a high-performance and miniaturized omnidirectional single-point photodetector (OSPD) is greatly desired. We report one design of OSPD using an aspheric lens, which achieves an enhanced reception angle of -5 deg to 45 deg in vertical and 360 deg in horizontal. As the heart of our OSPD, the aspheric lens is designed in a geometric model and optimized by LightTools Software, which enables the reflection of a wide-angle incident light beam into the single-point photodiode. The performance of home-made OSPD is characterized with working distances from 1 to 13 m and further analyzed utilizing developed a geometric model. The experimental and analytic results verify that our device is highly suitable for large-scale coordinate metrology. The developed device also holds great potential in various applications such as omnidirectional vision sensor, indoor global positioning system, and optical wireless communication systems.

Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

PubMed

Abd-Elhamid, T H; Conway, M L; Sinning, A R

2017-10-01

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. © 2017 Blackwell Verlag GmbH.

Left Ventricular Assist Devices: The Adolescence of a Disruptive Technology.

PubMed

Pinney, Sean P

2015-10-01

Clinical outcomes for patients with advanced heart failure receiving left ventricular assist devices are driven by appropriate patient selection, refined surgical technique, and coordinated medical care. Perhaps even more important is innovative pump design. The introduction and widespread adoption of continuous-flow ventricular assist devices has led to a paradigm shift within the field of mechanical circulatory support, making the promise of lifetime device therapy closer to reality. The disruption caused by this new technology, on the one hand, produced meaningful improvements in patient survival and quality of life, but also introduced new clinical challenges, such as bleeding, pump thrombosis, and acquired valvular heart disease. Further evolution within this field will require financial investment to sustain innovation leading to a fully implantable, durable, and cost-effective pump for a larger segment of patients with advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationships between Motor and Executive Functions and the Effect of an Acute Coordinative Intervention on Executive Functions in Kindergartners

PubMed Central

Stein, Marion; Auerswald, Max; Ebersbach, Mirjam

2017-01-01

There is growing evidence indicating positive, causal effects of acute physical activity on cognitive performance of school children, adolescents, and adults. However, only a few studies examined these effects in kindergartners, even though correlational studies suggest moderate relationships between motor and cognitive functions in this age group. One aim of the present study was to examine the correlational relationships between motor and executive functions among 5- to 6-year-olds. Another aim was to test whether an acute coordinative intervention, which was adapted to the individual motor functions of the children, causally affected different executive functions (i.e., motor inhibition, cognitive inhibition, and shifting). Kindergartners (N = 102) were randomly assigned either to a coordinative intervention (20 min) or to a control condition (20 min). The coordination group performed five bimanual exercises (e.g., throwing/kicking balls onto targets with the right and left hand/foot), whereas the control group took part in five simple activities that hardly involved coordination skills (e.g., stamping). Children’s motor functions were assessed with the Movement Assessment Battery for Children 2 (Petermann, 2009) in a pre-test (T1), 1 week before the intervention took place. Motor inhibition was assessed with the Simon says task (Carlson and Wang, 2007), inhibition and shifting were assessed with the Hearts and Flowers task (Davidson et al., 2006) in the pre-test and again in a post-test (T2) immediately after the interventions. Results revealed significant correlations between motor functions and executive functions (especially shifting) at T1. There was no overall effect of the intervention. However, explorative analyses indicated a three-way interaction, with the intervention leading to accuracy gains only in the motor inhibition task and only if it was tested directly after the intervention. As an unexpected effect, this result needs to be treated with caution but may indicate that the effect of acute coordinative exercise is temporally limited and emerges only for motor inhibition, but not for cognitive inhibition or shifting. More generally, in contrast to other studies including older participants and endurance exercises, no general effect of an acute coordinative intervention on executive functions was revealed for kindergartners. PMID:28611709

Strategies of biochemical adaptation for hibernation in a South American marsupial Dromiciops gliroides: 1. Mitogen-activated protein kinases and the cell stress response.

PubMed

Wijenayake, Sanoji; Luu, Bryan E; Zhang, Jing; Tessier, Shannon N; Quintero-Galvis, Julian F; Gaitán-Espitia, Juan Diego; Nespolo, Roberto F; Storey, Kenneth B

2017-12-14

Hibernation is a period of torpor and heterothermy that is typically associated with a strong reduction in metabolic rate, global suppression of transcription and translation, and upregulation of various genes/proteins that are central to the cellular stress response such as protein kinases, antioxidants, and heat shock proteins. The current study examined cell signaling cascades in hibernating monito del monte, Dromiciops gliroides, a South American marsupial of the Order Microbiotheria. Responses to hibernation by members of the mitogen-activated protein kinase (MAPK) pathways, and their roles in coordinating hibernator metabolism were examined in liver, kidney, heart and brain of control and versus hibernating (4days continuous torpor) D. gliroides. The targets evaluated included key protein kinases in their activated phosphorylated forms (p-ERK/MAPK 1/2, p-MEK1, p-MSK1, p-p38, p-JNK) and related target proteins (p-CREB 2, p-ATF2, p-c-Jun and p-p53). Liver exhibited a strong coordinated response by MAPK members to hibernation with significant increases in protein phosphorylation levels of p-MEK1, p-ERK/MAPK1/2, p-MSK1, p-JNK and target proteins c-Jun, and p-ATF2, all combining to signify a strong activation of MAPK signaling during hibernation. Kidney also showed activation of MAPK cascades with significant increases in p-MEK1, p-ERK/MAPK1/2, p-p38, and p-c-Jun levels in hibernating animals. By contrast, responses by heart and brain indicated reduced MAPK pathway function during torpor with reduced phosphorylation of targets including p-ERK/MAPK 1/2 in both tissues as well as lower p-p38 and p-JNK content in heart. Overall, the data indicate a vital role for MAPK signaling in regulating the cell stress response during marsupial hibernation. Copyright © 2017 Elsevier Inc. All rights reserved.

Metronome Use for Coordination of Breaths and Cardiac Compressions Delivered by Minimally-Trained Caregivers During Two-Person CPR

NASA Technical Reports Server (NTRS)

Hurst, Victor, IV; West, Sarah; Austin, Paul; Branson, Richard; Beck, George

2005-01-01

Astronaut crew medical officers (CMO) aboard the International Space Station (ISS) receive 40 hours of medical training over 18 months before each mission, including two-person cardiopulmonary resuscitation (2CPR) as recommended by the American Heart Association (AHA). Recent studies have concluded that the use of metronomic tones improves the coordination of 2CPR by trained clinicians. 2CPR performance data for minimally-trained caregivers has been limited. The goal of this study was to determine whether use of a metronome by minimally-trained caregivers (CMO analogues) would improve 2CPR performance. 20 pairs of minimally-trained caregivers certified in 2CPR via AHA guidelines performed 2CPR for 4 minutes on an instrumented manikin using 3 interventions: 1) Standard 2CPR without a metronome [NONE], 2) Standard 2CPR plus a metronome for coordinating compression rate only [MET], 3) Standard 2CPR plus a metronome for coordinating both the compression rate and ventilation rate [BOTH]. Caregivers were evaluated for their ability to meet the AHA guideline of 32 breaths-240 compressions in 4 minutes. All (100%) caregivers using the BOTH intervention provided the required number of ventilation breaths as compared with the NONE caregivers (10%) and MET caregivers (0%). For compressions, 97.5% of the BOTH caregivers were not successful in meeting the AHA compression guideline; however, an average of 238 compressions of the desired 240 were completed. None of the caregivers were successful in meeting the compression guideline using the NONE and MET interventions. This study demonstrates that use of metronomic tones by minimally-trained caregivers for coordinating both compressions and breaths improves 2CPR performance. Meeting the breath guideline is important to minimize air entering the stomach, thus decreasing the likelihood of gastric aspiration. These results suggest that manifesting a metronome for the ISS may augment the performance of 2CPR on orbit and thus may increase the level of care.

Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling.

PubMed

Essop, M Faadiel; Razeghi, Peter; McLeod, Chris; Young, Martin E; Taegtmeyer, Heinrich; Sack, Michael N

2004-02-06

Mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3) are postulated to contribute to antioxidant defense, nutrient partitioning, and energy efficiency in the heart. To distinguish isotype function in response to metabolic stress we measured cardiac mitochondrial function and cardiac UCP gene expression following chronic hypobaric hypoxia. Isolated mitochondrial O(2) consumption and ATP synthesis rate were reduced but respiratory coupling was unchanged compared to normoxic groups. Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (p<0.05) while UCP2 levels remained unchanged versus controls. Diminished UCP3 expression was associated with coordinate regulation of counter-regulatory metabolic genes. From these data, we propose a role for UCP3 in the regulation of fatty acid oxidation in the heart as opposed to uncoupling of mitochondria. Moreover, the divergent hypoxia-induced regulation of UCP2 and UCP3 supports distinct mitochondrial regulatory functions of these inner mitochondrial membrane proteins in the heart in response to metabolic stress.

A Triangulated Qualitative Study of Veteran Decision-Making to Seek Care During Heart Failure Exacerbation: Implications of Dual Health System Use

PubMed Central

Pope, Charlene A.; Davis, Boyd H.; Wine, Leticia; Nemeth, Lynne S.; Axon, Robert N.

2018-01-01

Among Veterans, heart failure (HF) contributes to frequent emergency department visits and hospitalization. Dual health care system use (dual use) occurs when Veterans Health Administration (VA) enrollees also receive care from non-VA sources. Mounting evidence suggests that dual use decreases efficiency and patient safety. This qualitative study used constructivist grounded theory and content analysis to examine decision making among 25 Veterans with HF, for similarities and differences between all-VA users and dual users. In general, all-VA users praised specific VA providers, called services helpful, and expressed positive capacity for managing HF. In addition, several Veterans who described inadvertent one-time non-VA health care utilization in emergent situations more closely mirrored all-VA users. By contrast, committed dual users more often reported unmet needs, nonresponse to VA requests, and faster services in non-VA facilities. However, a primary trigger for dual use was VA telephone referral for escalating symptoms, instead of care coordination or primary/specialty care problem-solving. PMID:29482411

Hemodynamic Improvement in Cardiac Resynchronization Does Not Require Improvement in Left Ventricular Rotation Mechanics

PubMed Central

Ashikaga, Hiroshi; Leclercq, Christophe; Wang, Jiangxia; Kass, David A.; McVeigh, Elliot R.

2010-01-01

Background Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. PMID:20478988

Educational level and the quality of life of heart failure patients: a longitudinal study.

PubMed

Barbareschi, Giorgio; Sanderman, Robbert; Leegte, Ivonne Lesman; van Veldhuisen, Dirk J; Jaarsma, Tiny

2011-01-01

Lower education in heart failure (HF) patients is associated with high levels of anxiety, limited physical functioning, and an increased risk of hospitalization. We examined whether educational level is related to longitudinal differences in quality of life (QoL) in HF patients. This research is a substudy of the Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure (COACH). QoL of 553 HF patients (mean age 69, 38% female, mean left ventricular ejection fraction 33%) was assessed during their hospitalization and at 4 follow-up measurements after discharge. In total 32% of the patients had very low, 24% low, 32% medium, and 12% high education. Patients with low educational levels reported the worst QoL. Significant differences between educational groups (P < .05) were only reported in physical functioning, social functioning, energy/fatigue, pain, and limitations in role functioning related to emotional problems. Longitudinal results show that a significantly higher proportion of high-educated patients improved in functional limitations related to emotional problems over time compared with lower-educated patients (P < .05). Patients with low educational levels reported the worst physical and functional condition. High-educated patients improved more than the other patients in functional limitations related to emotional problems over time. Low-educated patients may require different levels of intervention to improve their physical and functional condition. Copyright © 2011 Elsevier Inc. All rights reserved.

Evolution of a 90-day model of care for bundled episodic payments for congestive heart failure in home care.

PubMed

Feld, April; Madden-Baer, Rose; McCorkle, Ruth

2016-01-01

The Centers for Medicare and Medicaid Services Innovation Center's Episode-Based Payment initiatives propose a large opportunity to reduce cost from waste and variation and stand to align hospitals, physicians, and postacute providers in the redesign of care that achieves savings and improve quality. Community-based organizations are at the forefront of this care redesign through innovative models of care aimed at bridging gaps in care coordination and reducing hospital readmissions. This article describes a community-based provider's approach to participation under the Bundled Payments for Care Improvement initiative and a 90-day model of care for congestive heart failure in home care.

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice.

PubMed

Oda, Sayaka; Numaga-Tomita, Takuro; Kitajima, Naoyuki; Toyama, Takashi; Harada, Eri; Shimauchi, Tsukasa; Nishimura, Akiyuki; Ishikawa, Tatsuya; Kumagai, Yoshito; Birnbaumer, Lutz; Nishida, Motohiro

2017-08-08

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates.

PubMed

Taylor, Edwin W; Leite, Cleo A C; Sartori, Marina R; Wang, Tobias; Abe, Augusto S; Crossley, Dane A

2014-03-01

Heart rate in vertebrates is controlled by activity in the autonomic nervous system. In spontaneously active or experimentally prepared animals, inhibitory parasympathetic control is predominant and is responsible for instantaneous changes in heart rate, such as occur at the first air breath following a period of apnoea in discontinuous breathers like inactive reptiles or species that surface to air breathe after a period of submersion. Parasympathetic control, exerted via fast-conducting, myelinated efferent fibres in the vagus nerve, is also responsible for beat-to-beat changes in heart rate such as the high frequency components observed in spectral analysis of heart rate variability. These include respiratory modulation of the heartbeat that can generate cardiorespiratory synchrony in fish and respiratory sinus arrhythmia in mammals. Both may increase the effectiveness of respiratory gas exchange. Although the central interactions generating respiratory modulation of the heartbeat seem to be highly conserved through vertebrate phylogeny, they are different in kind and location, and in most species are as yet little understood. The heart in vertebrate embryos possesses both muscarinic cholinergic and β-adrenergic receptors very early in development. Adrenergic control by circulating catecholamines seems important throughout development. However, innervation of the cardiac receptors is delayed and first evidence of a functional cholinergic tonus on the heart, exerted via the vagus nerve, is often seen shortly before or immediately after hatching or birth, suggesting that it may be coordinated with the onset of central respiratory rhythmicity and subsequent breathing.

75 FR 28032 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... Coordinating Center. Date: June 4, 2010. Time: 1 p.m. to 2 p.m. Agenda: To review and evaluate contract..., NHLBI DNA Resequencing and Genotyping (RS&G) Service: Laboratory Center(s). Date: June 4, 2010. Time: 2... Career Enhancement Awards. Date: June 8-9, 2010. Time: 8 a.m. to 5 p.m. Agenda: To review and evaluate...

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

PubMed Central

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-01-01

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling.

PubMed

Ni, Yan G; Berenji, Kambeez; Wang, Na; Oh, Misook; Sachan, Nita; Dey, Asim; Cheng, Jun; Lu, Guangrong; Morris, David J; Castrillon, Diego H; Gerard, Robert D; Rothermel, Beverly A; Hill, Joseph A

2006-09-12

Cellular hypertrophy requires coordinated regulation of progrowth and antigrowth mechanisms. In cultured neonatal cardiomyocytes, Foxo transcription factors trigger an atrophy-related gene program that counters hypertrophic growth. However, downstream molecular events are not yet well defined. Here, we report that expression of either Foxo1 or Foxo3 in cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist-induced hypertrophic growth. Consistent with these results, Foxo proteins decrease calcineurin phosphatase activity and repress both basal and hypertrophic agonist-induced expression of MCIP1.4, a direct downstream target of the calcineurin/NFAT pathway. Furthermore, hearts from Foxo3-null mice exhibit increased MCIP1.4 abundance and a hypertrophic phenotype with normal systolic function at baseline. Together, these results suggest that Foxo proteins repress cardiac growth at least in part through inhibition of the calcineurin/NFAT pathway. Given that hypertrophic growth of the heart occurs in multiple contexts, our findings also suggest that certain hypertrophic signals are capable of overriding the antigrowth program induced by Foxo. Consistent with this, multiple hypertrophic agonists triggered inactivation of Foxo proteins in cardiomyocytes through a mechanism requiring the PI3K/Akt pathway. In addition, both Foxo1 and Foxo3 are phosphorylated and consequently inactivated in hearts undergoing hypertrophic growth induced by hemodynamic stress. This study suggests that inhibition of the calcineurin/NFAT signaling cascade by Foxo and release of this repressive action by the PI3K/Akt pathway are important mechanisms whereby Foxo factors govern cell growth in the heart.

Disease management in the treatment of patients with chronic heart failure who have universal access to health care: a randomized controlled trial.

PubMed

Kalter-Leibovici, Ofra; Freimark, Dov; Freedman, Laurence S; Kaufman, Galit; Ziv, Arnona; Murad, Havi; Benderly, Michal; Silverman, Barbara G; Friedman, Nurit; Cukierman-Yaffe, Tali; Asher, Elad; Grupper, Avishay; Goldman, Dorit; Amitai, Miriam; Matetzky, Shlomi; Shani, Mordechai; Silber, Haim

2017-05-01

The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies. In this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists. The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center. During the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0-5.0) years among patients assigned to disease management, and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure. Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up. This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care. Clinicaltrials.gov identifier: NCT00533013 . Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.

Physiological analysis to quantify training load in badminton.

PubMed Central

Majumdar, P; Khanna, G L; Malik, V; Sachdeva, S; Arif, M; Mandal, M

1997-01-01

OBJECTIVE: To estimate the training load of specific on court training regimens based on the magnitude of variation of heart rate-lactate response during specific training and to determine the magnitude of variation of biochemical parameters (urea, uric acid, and creatine phosphokinase (CPK)) 12 hours after the specific training programme so as to assess training stress. METHODS: The study was conducted on six national male badminton players. Maximum oxygen consumption (VO2), ventilation (VE), heart rate, and respiratory quotient were measured by a protocol of graded treadmill exercise. Twelve training sessions and 35 singles matches were analysed. Heart rate and blood lactate were monitored during technical training routines and match play. Fasting blood samples collected on two occasions--that is, during off season and 12 hours after specific training--were analysed for serum urea, uric acid, and CPK. RESULTS: Analysis of the on court training regimens showed lactate values of 8-10.5 mmol/l in different phases. The percentage of maximum heart rate ranged from 82% to 100%. Urea, uric acid, and CPK activity showed significant changes from (mean (SD)) 4.93 (0.75) mmol/l to 5.49 (0.84) mmol/l, 0.23 (0.04) to 0.33 (0.06) mmol/l, and 312 (211.8) to 363 (216.4) IU/l respectively. CONCLUSION: Maximum lactate reported in the literature ranges from 3-6 mmol/l. Comparatively high lactate values and high percentage of maximum heart rate found in on court training show a considerable stress on muscular and cardiovascular system. The training load needs appropriate monitoring to avoid over-training. Workouts that are too intensive may interfere with coordination, a factor that is important in sports requiring highly technical skill such as badminton. PMID:9429015

Examining the Use of a Social Media Campaign to Increase Engagement for the American Heart Association 2017 Resuscitation Science Symposium.

PubMed

Leary, Marion; McGovern, Shaun; Dainty, Katie N; Doshi, Ankur A; Blewer, Audrey L; Kurz, Michael C; Rittenberger, Jon C; Hazinski, Mary Fran; Reynolds, Joshua C

2018-04-13

The Resuscitation Science Symposium (ReSS) is the dedicated international forum for resuscitation science at the American Heart Association's Scientific Sessions. In an attempt to increase curated content and social media presence during ReSS 2017, the Journal of the American Heart Association (JAHA) coordinated an inaugural social media campaign. Before ReSS, 8 resuscitation science professionals were recruited from a convenience sample of attendees at ReSS 2017. Each blogger was assigned to either a morning or an afternoon session, responsible for "live tweeting" with the associated hashtags #ReSS17 and #AHA17. Twitter analytics from the 8 bloggers were collected from November 10 to 13, 2017. The primary outcome was Twitter impressions. Secondary outcomes included Twitter engagement and Twitter engagement rate. In total, 8 bloggers (63% male) generated 591 tweets that garnered 261 050 impressions, 8013 engagements, 928 retweets, 1653 likes, 292 hashtag clicks, and a median engagement rate of 2.4%. Total engagement, likes, and hashtag clicks were highest on day 2; total impressions were highest on day 3, and retweets were highest on day 4. Total impressions were highly correlated with the total number of tweets ( r =0.87; P =0.005) and baseline number of Twitter followers for each blogger ( r =0.78; P =0.02). In this inaugural social media campaign for the 2017 American Heart Association ReSS, the degree of online engagement with this content by end users was quite good when evaluated by social media standards. Benchmarks for end-user interactions in the scientific community are undefined and will require further study. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Survey of nongovernmental organizations providing pediatric cardiovascular care in low- and middle-income countries.

PubMed

Nguyen, Nguyenvu; Jacobs, Jeffrey P; Dearani, Joseph A; Weinstein, Samuel; Novick, William M; Jacobs, Marshall L; Massey, Jeremy; Pasquali, Sara K; Walters, Henry L; Drullinsky, David; Stellin, Giovanni; Tchervenkov, Christo I

2014-04-01

Nearly 90% of the children with heart disease in low- and middle-income countries (LMICs) cannot access cardiovascular (CV) services. Limitations include inadequate financial, human, and infrastructure resources. Nongovernmental organizations (NGOs) have played crucial roles in providing clinical services and infrastructure supports to LMICs CV programs; however, these outreach efforts are dispersed, inadequate, and lack coordination. A survey was sent to members of the World Society for Pediatric and Congenital Heart Society and PediHeart. A clearinghouse was created to provide information on NGO structures, geographic reach, and scope of services. The survey identified 80 NGOs supporting CV programs in 92 LMICs. The largest outreach efforts were in South and Central America (42%), followed by Africa (18%), Europe (17%), Asia (17%), and Asia-Western Pacific (6%). Most NGOs (51%) supported two to five outreach missions per year. The majority (87%) of NGOs provided education, diagnostics, and surgical or catheter-based interventions. Working jointly with LMIC partners, 59% of the NGOs performed operations in children and infants; 41% performed nonbypass neonatal operations. Approximately a quarter (26%) reported that partner sites do not perform interventions in between missions. Disparity and inadequacy in pediatric CV services remain an important problem for LMICs. A global consensus and coordinated efforts are needed to guide strategies on the development of regional centers of excellence, a global outcome database, and a CV program registry. Future efforts should be held accountable for impacts such as growth in the number of independent LMIC programs as well as reduction in mortality and patient waiting lists.

Survey of Nongovernmental Organizations Providing Pediatric Cardiovascular Care in Low- and Middle-Income Countries

PubMed Central

Nguyen, Nguyenvu; Jacobs, Jeffrey P.; Dearani, Joseph A.; Weinstein, Samuel; Novick, William M.; Jacobs, Marshall L.; Massey, Jeremy; Pasquali, Sara K.; Walters, Henry L.; Drullinsky, David; Stellin, Giovanni; Tchervenkov, Christo I.

2014-01-01

Background Nearly 90% of the children with heart disease in low- and middle-income countries (LMICs) cannot access cardiovascular (CV) services. Limitations include inadequate financial, human, and infrastructure resources. Nongovernmental organizations (NGOs) have played crucial roles in providing clinical services and infrastructure supports to LMICs CV programs; however, these outreach efforts are dispersed, inadequate, and lack coordination. Methods A survey was sent to members of the World Society for Pediatric and Congenital Heart Society and PediHeart. Results A clearinghouse was created to provide information on NGO structures, geographic reach, and scope of services. The survey identified 80 NGOs supporting CV programs in 92 LMICs. The largest outreach efforts were in South and Central America (42%), followed by Africa (18%), Europe (17%), Asia (17%), and Asia-Western Pacific (6%). Most NGOs (51%) supported two to five outreach missions per year. The majority (87%) of NGOs provided education, diagnostics, and surgical or catheter-based interventions. Working jointly with LMIC partners, 59% of the NGOs performed operations in children and infants; 41% performed nonbypass neonatal operations. Approximately a quarter (26%) reported that partner sites do not perform interventions in between missions. Conclusions Disparity and inadequacy in pediatric CV services remain an important problem for LMICs. A global consensus and coordinated efforts are needed to guide strategies on the development of regional centers of excellence, a global outcome database, and a CV program registry. Future efforts should be held accountable for impacts such as growth in the number of independent LMIC programs as well as reduction in mortality and patient waiting lists. PMID:24668973

Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor.

PubMed

Howangyin, Kiave-Yune; Zlatanova, Ivana; Pinto, Cristina; Ngkelo, Anta; Cochain, Clément; Rouanet, Marie; Vilar, José; Lemitre, Mathilde; Stockmann, Christian; Fleischmann, Bernd K; Mallat, Ziad; Silvestre, Jean-Sébastien

2016-03-01

In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/-)/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis. After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart. © 2016 The Authors.

Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor

PubMed Central

Howangyin, Kiave-Yune; Zlatanova, Ivana; Pinto, Cristina; Ngkelo, Anta; Cochain, Clément; Rouanet, Marie; Vilar, José; Lemitre, Mathilde; Stockmann, Christian; Fleischmann, Bernd K.; Mallat, Ziad

2016-01-01

Background— In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. Methods and Results— We generated double-deficient mice for Mertk and Mfge8 (Mertk−/−/Mfge8−/−) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk−/−), or Mfge8-deficient (Mfge8−/−) animals, Mertk−/−/Mfge8−/− mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6CHigh and Low monocytes and macrophages. In parallel, Mertk−/−/Mfge8−/− bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6CHigh and Ly6CHow monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6CHigh/Ly6CLow monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre+/VEGFAfl/fl mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis. Conclusions— After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart. PMID:26819373

Potential interactions among linguistic, autonomic, and motor factors in speech.

PubMed

Kleinow, Jennifer; Smith, Anne

2006-05-01

Though anecdotal reports link certain speech disorders to increases in autonomic arousal, few studies have described the relationship between arousal and speech processes. Additionally, it is unclear how increases in arousal may interact with other cognitive-linguistic processes to affect speech motor control. In this experiment we examine potential interactions between autonomic arousal, linguistic processing, and speech motor coordination in adults and children. Autonomic responses (heart rate, finger pulse volume, tonic skin conductance, and phasic skin conductance) were recorded simultaneously with upper and lower lip movements during speech. The lip aperture variability (LA variability index) across multiple repetitions of sentences that varied in length and syntactic complexity was calculated under low- and high-arousal conditions. High arousal conditions were elicited by performance of the Stroop color word task. Children had significantly higher lip aperture variability index values across all speaking tasks, indicating more variable speech motor coordination. Increases in syntactic complexity and utterance length were associated with increases in speech motor coordination variability in both speaker groups. There was a significant effect of Stroop task, which produced increases in autonomic arousal and increased speech motor variability in both adults and children. These results provide novel evidence that high arousal levels can influence speech motor control in both adults and children. (c) 2006 Wiley Periodicals, Inc.

Care Coordination Challenges Among High-Needs, High-Costs Older Adults in a Medigap Plan

PubMed Central

Wells, Timothy S.; Bhattarai, Gandhi R.; Hawkins, Kevin; Cheng, Yan; Ruiz, Joann; Barnowski, Cynthia A.; Spivack, Barney; Yeh, Charlotte S.

2016-01-01

Purpose of the Study: Many adults 65 years or older have high health care needs and costs. Here, we describe their care coordination challenges. Primary Practice Setting: Individuals with an AARP Medicare Supplement Insurance plan insured by UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare Insurance Company of New York). Methodology and Sample: The three groups included the highest needs, highest costs (the “highest group”), the high needs, high costs (the “high group”), and the “all other group.” Eligibility was determined by applying an internally developed algorithm based upon a number of criteria, including hierarchical condition category score, the Optum ImpactPro prospective risk score, as well as diagnoses of coronary artery disease, congestive heart failure, or diabetes. Results: The highest group comprised 2%, although consumed 12% of health care expenditures. The high group comprised 20% and consumed 46% of expenditures, whereas the all other group comprised 78% and consumed 42% of expenditures. On average, the highest group had $102,798 in yearly health care expenditures, compared with $34,610 and $7,634 for the high and all other groups, respectively. Fifty-seven percent of the highest group saw 16 or more different providers annually, compared with 21% and 2% of the high and all other groups, respectively. Finally, 28% of the highest group had prescriptions from at least seven different providers, compared with 20% and 5% of the high and all other groups, respectively. Implications for Case Management Practice: Individuals with high health care needs and costs have visits to numerous health care providers and receive multiple prescriptions for pharmacotherapy. As a result, these individuals can become overwhelmed trying to manage and coordinate their health care needs. Care coordination programs may help these individuals coordinate their care. PMID:27301064

78 FR 63483 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... 7, 2013. Time: 8:00 a.m. to 2:00 p.m. Agenda: To review and evaluate grant applications. Place: The... Development Data Coordinating Center. Date: November 7, 2013. Time: 2:30 p.m. to 4:00 p.m. Agenda: To review... Institute Special Emphasis Panel; SBIR Phase IIB Bridge Awards. Date: November 8, 2013. Time: 8:00 a.m. to...

Cyanide binding to ferrous and ferric microperoxidase-11.

PubMed

Ascenzi, Paolo; Sbardella, Diego; Santucci, Roberto; Coletta, Massimo

2016-07-01

Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cytc). MP11 is characterized by a covalently linked solvent-exposed heme group, the heme-Fe atom being axially coordinated by a histidyl residue. Here, the reactions of ferrous and ferric MP11 (MP11-Fe(II) and MP11-Fe(III), respectively) with cyanide have been investigated from the kinetic and thermodynamic viewpoints, at pH 7.0 and 20.0 °C. Values of the second-order rate constant for cyanide binding to MP11-Fe(II) and MP11-Fe(III) are 4.5 M(-1) s(-1) and 8.9 × 10(3) M(-1) s(-1), respectively. Values of the first-order rate constant for cyanide dissociation from ligated MP11-Fe(II) and MP11-Fe(III) are 1.8 × 10(-1) s(-1) and 1.5 × 10(-3) s(-1), respectively. Values of the dissociation equilibrium constant for cyanide binding to MP11-Fe(II) and MP11-Fe(III) are 3.7 × 10(-2) and 1.7 × 10(-7) M, respectively, matching very well with those calculated from kinetic parameters so that no intermediate species seem to be involved in the ligand-binding process. The pH-dependence of cyanide binding to MP11-Fe(III) indicates that CN(-) is the only binding species. Present results have been analyzed in parallel with those of several heme-proteins, suggesting that (1) the ligand accessibility to the metal center and cyanide ionization may modulate the formation of heme-Fe-cyanide complexes, and (2) the general polarity of the heme pocket and/or hydrogen bonding of the heme-bound ligand may affect cyanide exit from the protein matrix. Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c. Penta-coordinated MP11 displays a very high reactivity towards cyanide, whereas the reactivity of hexa-coordinated horse heart cytochrome c is very low.

Bridging Computational Genetics and Vectorcardiography: A Robust Platform for the Early Detection of Heart Disease

NASA Astrophysics Data System (ADS)

Sridhar, S.

2017-12-01

By 2030, it is predicted that over 14 million people will die of heart disease annually, many of whom will discover their risk when it is too late to seek effective treatment or pursue lifestyle changes. In this research study, I sought to design a robust computational platform to gauge a patient's risk for cardiac diseases (CDs) based on demographics, genotype, and cardiac action potentials through machine learning, statistical analysis, and vectorcardiography. By analyzing previously published data, I discovered that certain polymorphisms in the ACE and MTHFR genes contribute significantly to CD risk. The deletion allele of the ACE insertion/deletion polymorphism increases ACE serum levels, promoting CD phenotypes. A point mutation in the MTHFR gene curbs the metabolism of folic acid, giving rise to CD phenotypes. I analyzed over 9000 British Medical Journal and American Heart Association patients to determine the CD risk associated with each ACE and MTHFR genotype. In the vectorcardiography phase of my study, I investigated trends in the maximal vectors of the QRS loop of the cardiac wave. Using a database with both normal and diseased vectorcardiographic action potentials, I plotted the maximal vectors on a 3D RAS coordinate plane to analyze their magnitude and direction. From the ACE datasets, I discovered that female patients over 45 and of Indian descent with two ACE deletion alleles exhibited the highest CD risk. Using this spectrum, I successfully constructed a neural network with an accuracy score of 0.867 that predicts CD risk based on ACE genotype, gender, region, and age. Investigation of the MTHFR genome showed that those with a homozygous mutated gene had a significantly higher CD risk. In my vectorcardiography study, I found that healthy QRS vectors pointed predominantly to the right-anterior region of the coordinate plane and exhibited short, consistent magnitudes. On the other hand, diseased vectors pointed to the left-posterior region and exhibited large, varying magnitudes. Since these vectors exhibited a stark dichotomy in orientation, I designed an SVM classifier that was able to distinguish between normal and diseased vectorcardiographs with an F1 score of 0.965. Overall, my neural network and SVM classifiers have the potential to enhance clinical CD diagnosis in developing nations.

The China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) retrospective heart failure study design

PubMed Central

Yu, Yuan; Zhang, Hongzhao; Li, Xi; Lu, Yuan; Masoudi, Frederick A; Li, Jing

2018-01-01

Introduction Heart failure (HF) is a leading cause of hospitalisation in China, which is experiencing a rapid increase in cardiovascular disease prevalence. Yet, little is known about current burden of disease, quality of care and treatment outcomes of HF in China. The objective of this paper is to describe the study methodology, data collection and abstraction, and progress to date of the China Patient-centered Evaluative Assessment of Cardiac Events 5 Retrospective Heart Failure Study (China PEACE 5r-HF). Methods and analysis The China PEACE 5r-HF Study will examine a nationally representative sample of more than 10 000 patient records hospitalised for HF in 2015 in China. The study is a retrospective cohort study. Patients have been selected using a two-stage sampling design stratified by economic–geographical regions. We will collect patient characteristics, diagnostic testing, treatments and in-hospital outcomes, including death and complications, and charges of hospitalisation. Data quality will be monitored by a central coordinating centre and will address case ascertainment, data abstraction and data management. As of October 2017, we have sampled 15 538 medical records from 189 hospitals, and have received 15 057 (96.9%) of these for data collection, and completed data abstraction and quality control on 7971. Ethics and dissemination The Central Ethics Committee at the Chinese National Center for Cardiovascular Diseases approved the study. All collaborating hospitals accepted central ethics committee approval with the exception of 15 hospitals, which obtained local approval by internal ethics committees. Findings will be disseminated in future peer-reviewed papers and will serve as a foundation for improving the care for HF in China. Trial registration number NCT02877914. PMID:29748344

Do disease management programs for patients with coronary heart disease make a difference? Experiences of nine practices.

PubMed

Walsh, Mary N; Simpson, Ross J; Wan, George J; Weiss, Thomas W; Alexander, Charles M; Markson, Leona E; Berger, Marc L; Pearson, Thomas A

2002-11-01

To observe the experience of 9 practice sites in implementing provider-defined disease management programs for coronary heart disease patients. Observational study of provider-defined practice improvement programs. Practices chose from a variety of interventions that included provider- and patient-based disease management tools. Data were collected at baseline, 6, and 12 months. Complete baseline, 6-month, and 12-month data were available for 586 patients (58% of the 1013 patients enrolled). Compared with baseline, 6-month data showed more patients whose total cholesterol was less than 200 mg/dL (56% to 76%; P < or = .001), whose low-density lipoprotein (LDL) cholesterol was less than 100 mg/dL (30% to 54%; P < or = .001), and whose high-density lipoprotein cholesterol was at least 35 mg/dL (75% to 81%; P < or = .001); who exercised rigorously for 30 minutes, 3 times a week (40% to 53%; P < or = .001); who used lipid medication (74% to 80%; P < or = .01); and who used aspirin (84% to 92%; P < or = .001). There were no significant improvements in triglyceride levels, blood pressure control, glycemic control among diabetes patients, smoking cessation, body mass index, and beta-blocker use. The 12-month results were similar to the 6-month results. Sites with a practice coordinator had the highest number of patients achieving their LDL goal (72% to 89%). There may be an opportunity to improve patient care by applying disease management principles with a variety of interventions. Dedicated personnel to help coordinate disease management programs may be critical to the success of such programs.

The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.

PubMed

Garrity, Deborah M; Childs, Sarah; Fishman, Mark C

2002-10-01

Holt-Oram syndrome is one of the autosomal dominant human "heart-hand" disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart. We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium. Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals.

Comorbid condition care quality in cancer survivors: role of primary care and specialty providers and care coordination.

PubMed

Snyder, Claire F; Frick, Kevin D; Herbert, Robert J; Blackford, Amanda L; Neville, Bridget A; Lemke, Klaus W; Carducci, Michael A; Wolff, Antonio C; Earle, Craig C

2015-12-01

The purpose of this study is to investigate provider specialty, care coordination, and cancer survivors' comorbid condition care. This retrospective cross-sectional Surveillance, Epidemiology, and End Results (SEER)-Medicare study included cancer survivors diagnosed in 2004, 2-3 years post-cancer diagnosis, in fee-for-service Medicare. We examined (1) provider specialties (primary care providers (PCPs), oncology specialists, other specialists) visited post-hospitalization, (2) role of provider specialties in chronic and acute condition management, and (3) an ambulatory care coordination measure. Outcome measures covered (1) visits post-hospitalization for nine conditions, (2) chronic disease management (lipid profile, diabetic eye exam, diabetic monitoring), and (3) acute condition management (electrocardiogram (EKG) for congestive heart failure (CHF), imaging for CHF, EKG for transient ischemic attack, cholecystectomy, hip fracture repair). Among 8661 cancer survivors, patients were more likely to visit PCPs than oncologists or other specialists following hospitalizations for 8/9 conditions. Patients visiting a PCP (vs. not) were more likely to receive recommended care for 3/3 chronic and 1/5 acute condition indicators. Patients visiting a nother specialist (vs. not) were more likely to receive recommended care for 3/3 chronic and 2/5 acute condition indicators. Patients visiting an oncology specialist (vs. not) were more likely to receive recommended care on 2/3 chronic indicators and less likely to receive recommended care on 1/5 acute indicators. Patients at greatest risk for poor coordination were more likely to receive appropriate care on 4/6 indicators. PCPs are central to cancer survivors' non-cancer comorbid condition care quality. Implications for Cancer Survivors PCP involvement in cancer survivors' care should be promoted.

Differential effects of professional leaders on health care teams in chronic disease management groups.

PubMed

Wholey, Douglas R; Disch, Joanne; White, Katie M; Powell, Adam; Rector, Thomas S; Sahay, Anju; Heidenreich, Paul A

2014-01-01

Leadership by health care professionals is likely to vary because of differences in the social contexts within which they are situated, socialization processes and societal expectations, education and training, and the way their professions define and operationalize key concepts such as teamwork, collaboration, and partnership. This research examines the effect of the nurse and physician leaders on interdependence and encounter preparedness in chronic disease management practice groups. The aim of this study was to examine the effect of complementary leadership by nurses and physicians involved in jointly producing a health care service on care team functioning. The design is a retrospective observational study based on survey data. The unit of analysis is heart failure care groups in U.S. Veterans Health Administration medical centers. Survey and administrative data were collected in 2009 from 68 Veterans Health Administration medical centers. Key variables include nurse and physician leadership, interdependence, psychological safety, coordination, and encounter preparedness. Reliability and validity of survey measures were assessed with exploratory factor analysis and Cronbach alphas. Multivariate analyses tested hypotheses. Professional leadership by nurses and physicians is related to encounter preparedness by different paths. Nurse leadership is associated with greater team interdependence, and interdependence is positively associated with respect. Physician leadership is positively associated with greater psychological safety, respect, and shared goals but is not associated with interdependence. Respect is associated with involvement in learning activities, and shared goals are associated with coordination. Coordination and involvement in learning activities are positively associated with encounter preparedness. By focusing on increasing interdependence and a constructive climate, nurse and physician leaders have the opportunity to increase care coordination and involvement in learning activities.

Assessment of the swallowing function in older individuals referred to myocardial revascularization surgery.

PubMed

Dantas, Mara de Oliveira Rodrigues Luiz; Auler, José Otávio Costa; Andrade, Claudia Regina Furquim de

2010-01-01

Swallowing evaluation of older individuals with coronary disease referred to heart surgery. To identify the characteristics of the swallowing function in older individuals referred to myocardial revascularization surgery (MR), using an evaluating protocol composed by a water test, cervical auscultation and pulse oximetry. The Assessment Protocol for Dysphagia Risk through a Combined Swallowing test and Vital Signs monitoring was used (PADTC)--measurements of HR and SpO2 (heart rate and oxygen saturation), water swallowing test with 1, 3, 5, 10, 15 e 20 ml, measurement of respiratory rate and cervical auscultation. The electronic stethoscope was used to analyze the number of swallows, response time and swallowing sound classification. In the Research Group (RG) older individuals with heart disease who were referred to MR were included. In the Control Group (CG) healthy older individuals were included. 38 older individuals were evaluated in the RG (mean age 68 years). In the CG, 30 older individuals were evaluated (mean age 70 years). There was a significant difference for the swallowing response time in older individuals with heart disease who presented HR below 60: swallowing response was shorter for 3 ml, 10 ml, 15 ml e 20 ml. HR was lower for individuals with heart disease. No significant difference was found between the groups for the other analyzed parameters. Older individuals with heart disease presented differences in the swallowing function when compared to healthy older individuals. Older individuals with heart disease presented alterations in the temporal coordination between breathing and swallowing, thus indicating risk for dysphagia.

Simulation of blood flow through an artificial heart

NASA Technical Reports Server (NTRS)

Kiris, Cetin; Chang, I-Dee; Rogers, Stuart E.; Kwak, Dochan

1991-01-01

A numerical simulation of the incompressible viscous flow through a prosthetic tilting disk heart valve is presented in order to demonstrate the current capability to model unsteady flows with moving boundaries. Both steady state and unsteady flow calculations are done by solving the incompressible Navier-Stokes equations in 3-D generalized curvilinear coordinates. In order to handle the moving boundary problems, the chimera grid embedding scheme which decomposes a complex computational domain into several simple subdomains is used. An algebraic turbulence model for internal flows is incorporated to reach the physiological values of Reynolds number. Good agreement is obtained between the numerical results and experimental measurements. It is found that the tilting disk valve causes large regions of separated flow, and regions of high shear.

Computation of incompressible viscous flows through artificial heart devices with moving boundaries

NASA Technical Reports Server (NTRS)

Kiris, Cetin; Rogers, Stuart; Kwak, Dochan; Chang, I.-DEE

1991-01-01

The extension of computational fluid dynamics techniques to artificial heart flow simulations is illustrated. Unsteady incompressible Navier-Stokes equations written in 3-D generalized curvilinear coordinates are solved iteratively at each physical time step until the incompressibility condition is satisfied. The solution method is based on the pseudo compressibility approach and uses an implicit upwind differencing scheme together with the Gauss-Seidel line relaxation method. The efficiency and robustness of the time accurate formulation of the algorithm are tested by computing the flow through model geometries. A channel flow with a moving indentation is computed and validated with experimental measurements and other numerical solutions. In order to handle the geometric complexity and the moving boundary problems, a zonal method and an overlapping grid embedding scheme are used, respectively. Steady state solutions for the flow through a tilting disk heart valve was compared against experimental measurements. Good agreement was obtained. The flow computation during the valve opening and closing is carried out to illustrate the moving boundary capability.

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

PubMed Central

Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

2015-01-01

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

Modulation of gene expression in heart and liver of hibernating black bears (Ursus americanus)

PubMed Central

2011-01-01

Background Hibernation is an adaptive strategy to survive in highly seasonal or unpredictable environments. The molecular and genetic basis of hibernation physiology in mammals has only recently been studied using large scale genomic approaches. We analyzed gene expression in the American black bear, Ursus americanus, using a custom 12,800 cDNA probe microarray to detect differences in expression that occur in heart and liver during winter hibernation in comparison to summer active animals. Results We identified 245 genes in heart and 319 genes in liver that were differentially expressed between winter and summer. The expression of 24 genes was significantly elevated during hibernation in both heart and liver. These genes are mostly involved in lipid catabolism and protein biosynthesis and include RNA binding protein motif 3 (Rbm3), which enhances protein synthesis at mildly hypothermic temperatures. Elevated expression of protein biosynthesis genes suggests induction of translation that may be related to adaptive mechanisms reducing cardiac and muscle atrophies over extended periods of low metabolism and immobility during hibernation in bears. Coordinated reduction of transcription of genes involved in amino acid catabolism suggests redirection of amino acids from catabolic pathways to protein biosynthesis. We identify common for black bears and small mammalian hibernators transcriptional changes in the liver that include induction of genes responsible for fatty acid β oxidation and carbohydrate synthesis and depression of genes involved in lipid biosynthesis, carbohydrate catabolism, cellular respiration and detoxification pathways. Conclusions Our findings show that modulation of gene expression during winter hibernation represents molecular mechanism of adaptation to extreme environments. PMID:21453527

Comprehensive electronic medical record implementation levels not associated with 30-day all-cause readmissions within Medicare beneficiaries with heart failure.

PubMed

Patterson, M E; Marken, P; Zhong, Y; Simon, S D; Ketcherside, W

2014-01-01

Regulatory standards for 30-day readmissions incentivize hospitals to improve quality of care. Implementing comprehensive electronic health record systems potentially decreases readmission rates by improving medication reconciliation at discharge, demonstrating the additional benefits of inpatient EHRs beyond improved safety and decreased errors. To compare 30-day all-cause readmission incidence rates within Medicare fee-for-service with heart failure discharged from hospitals with full implementation levels of comprehensive EHR systems versus those without. This retrospective cohort study uses data from the American Hospital Association Health IT survey and Medicare Part A claims to measure associations between hospital EHR implementation levels and beneficiary readmissions. Multivariable Cox regressions estimate the hazard ratio of 30-day all-cause readmissions within beneficiaries discharged from hospitals implementing comprehensive EHRs versus those without, controlling for beneficiary health status and hospital organizational factors. Propensity scores are used to account for selection bias. The proportion of heart failure patients with 30-day all-cause readmissions was 30%, 29%, and 32% for those discharged from hospitals with full, some, and no comprehensive EHR systems. Heart failure patients discharged from hospitals with fully implemented comprehensive EHRs compared to those with no comprehensive EHR systems had equivalent 30-day readmission incidence rates (HR = 0.97, 95% CI 0.73 - 1.3). Implementation of comprehensive electronic health record systems does not necessarily improve a hospital's ability to decrease 30-day readmission rates. Improving the efficiency of post-acute care will require more coordination of information systems between inpatient and ambulatory providers.

Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

PubMed Central

Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F.; Sadoshima, Junichi; Tian, Bin

2011-01-01

Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842

Foxo Transcription Factors Blunt Cardiac Hypertrophy by Inhibiting Calcineurin Signaling

PubMed Central

Ni, Yan G.; Berenji, Kambeez; Wang, Na; Oh, Misook; Sachan, Nita; Dey, Asim; Cheng, Jun; Lu, Guangrong; Morris, David J.; Castrillon, Diego H.; Gerard, Robert D.; Rothermel, Beverly A.; Hill, Joseph A.

2014-01-01

Background Cellular hypertrophy requires coordinated regulation of progrowth and antigrowth mechanisms. In cultured neonatal cardiomyocytes, Foxo transcription factors trigger an atrophy-related gene program that counters hypertrophic growth. However, downstream molecular events are not yet well defined. Methods and Results Here, we report that expression of either Foxo1 or Foxo3 in cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist-induced hypertrophic growth. Consistent with these results, Foxo proteins decrease calcineurin phosphatase activity and repress both basal and hypertrophic agonist-induced expression of MCIP1.4, a direct downstream target of the calcineurin/NFAT pathway. Furthermore, hearts from Foxo3-null mice exhibit increased MCIP1.4 abundance and a hypertrophic phenotype with normal systolic function at baseline. Together, these results suggest that Foxo proteins repress cardiac growth at least in part through inhibition of the calcineurin/NFAT pathway. Given that hypertrophic growth of the heart occurs in multiple contexts, our findings also suggest that certain hypertrophic signals are capable of overriding the antigrowth program induced by Foxo. Consistent with this, multiple hypertrophic agonists triggered inactivation of Foxo proteins in cardiomyocytes through a mechanism requiring the PI3K/Akt pathway. In addition, both Foxo1 and Foxo3 are phosphorylated and consequently inactivated in hearts undergoing hypertrophic growth induced by hemodynamic stress. Conclusions This study suggests that inhibition of the calcineurin/NFAT signaling cascade by Foxo and release of this repressive action by the PI3K/Akt pathway are important mechanisms whereby Foxo factors govern cell growth in the heart. PMID:16952979

Effect of spironolactone on 30-day death and heart failure rehospitalization (from the COACH Study).

PubMed

Maisel, Alan; Xue, Yang; van Veldhuisen, Dirk J; Voors, Adriaan A; Jaarsma, Tiny; Pang, Peter S; Butler, Javed; Pitt, Bertram; Clopton, Paul; de Boer, Rudolf A

2014-09-01

The aim of our study is to investigate the effect of spironolactone on 30-day outcomes in patients with acute heart failure (AHF) and the association between treatment and outcomes stratified by biomarkers. We conducted a secondary analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone therapy was initiated and terminated at the discretion of the treating physician; 30-day outcomes were compared between patients who were treated with spironolactone and those who were not. Outcomes with spironolactone therapy were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at discharge (158 new and 139 continued). There were 19 deaths and 30 HF rehospitalizations among 46 patients by 30 days. Patients discharged on spironolactone had significantly less 30-day event (hazard ratio 0.538, p = 0.039) after adjustment for multiple risk factors. Initiation of spironolactone in patients who were not on spironolactone before admission was associated with a significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival benefit of spironolactone was more prominent in patient groups with elevations of creatinine, N-terminal pro-B-type natriuretic peptide, ST2, or galectin-3. In conclusion, AHF patients who received spironolactone during hospitalization had significantly fewer 30-day mortality and HF rehospitalizations, especially in high-risk patients. Copyright © 2014 Elsevier Inc. All rights reserved.

DoD And VA Health Care: Federal Recovery Coordination Program Continues to Expand But Faces Significant Challenges

DTIC Science & Technology

2011-03-01

FRCP) Enrollees, September 2010 Diagnoses Percentage of enrollees Traumatic brain injury 54 Psychological diagnosis 43 Orthopedic injury 25...analysis of FRCP data. Note: These diagnoses may not represent each enrollee’s primary medical diagnosis . Additionally, approximately 70 percent of...FRCP enrollees have more than one diagnosis . a“Medical diagnosis ” includes diagnoses such as stroke, heart attack, and cancer. b“Other” includes

[Cardiauvergne is a remote monitoring and care coordination service for patients with severe heart failure].

PubMed

Boiteux, Marie-Claire; Rey, Philippe; Cadiou, Françoise; Chauvet, Caroline

2016-11-01

Since 2011, thanks to the cooperation of frontline healthcare professionals, it has provided care to more than 1 200 patients across the Auvergne health region. The organisation, blending telemedicine and human contact, has made this initiative a successful example of how the boundaries between community and hospital healthcare can be removed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months.

PubMed

Haley, David W; Grunau, Ruth E; Weinberg, Joanne; Keidar, Adi; Oberlander, Tim F

2010-04-01

We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants. Copyright 2009 Elsevier Inc. All rights reserved.

Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

PubMed

Jollis, James G; Al-Khalidi, Hussein R; Roettig, Mayme L; Berger, Peter B; Corbett, Claire C; Dauerman, Harold L; Fordyce, Christopher B; Fox, Kathleen; Garvey, J Lee; Gregory, Tammy; Henry, Timothy D; Rokos, Ivan C; Sherwood, Matthew W; Suter, Robert E; Wilson, B Hadley; Granger, Christopher B

2016-08-02

Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans. We established leadership teams, coordinated protocols, and provided regular feedback for 484 hospitals and 1253 emergency medical services (EMS) agencies in 16 regions across the United States. Between July 2012 and December 2013, 23 809 patients presented with acute STEMI (direct to percutaneous coronary intervention hospital: 11 765 EMS transported and 6502 self-transported; 5542 transferred). EMS-transported patients differed from self-transported patients in symptom onset to first medical contact time (median, 47 versus 114 minutes), incidence of cardiac arrest (10% versus 3%), shock on admission (11% versus 3%), and in-hospital mortality (8% versus 3%; P<0.001 for all comparisons). There was a significant increase in the proportion of patients meeting guideline goals of first medical contact-to-device time, including those directly presenting via EMS (50% to 55%; P<0.001) and transferred patients (44%-48%; P=0.002). Despite regional variability, the greatest gains occurred among patients in the 5 most improved regions, increasing from 45% to 57% (direct EMS; P<0.001) and 38% to 50% (transfers; P<0.001). This Mission: Lifeline STEMI Systems Accelerator demonstration project represents the largest national effort to organize regional STEMI care. By focusing on first medical contact-to-device time, coordinated treatment protocols, and regional data collection and reporting, we were able to increase significantly the proportion of patients treated within guideline goals. © 2016 American Heart Association, Inc.

Adult cardiothoracic transplant nursing: an ISHLT consensus document on the current adult nursing practice in heart and lung transplantation.

PubMed

Coleman, Bernice; Blumenthal, Nancy; Currey, Judy; Dobbels, Fabienne; Velleca, Angela; Grady, Kathleen L; Kugler, Christiane; Murks, Catherine; Ohler, Linda; Sumbi, Christine; Luu, Minh; Dark, John; Kobashigawa, Jon; White-Williams, Connie

2015-02-01

The role of nurses in cardiothoracic transplantation has evolved over the last 25 years. Transplant nurses work in a variety of roles in collaboration with multidisciplinary teams to manage complex pre- and post-transplantation issues. There is lack of clarity and consistency regarding required qualifications to practice transplant nursing, delineation of roles and adequate levels of staffing. A consensus conference with workgroup sessions, consisting of 77 nurse participants with clinical experience in cardiothoracic transplantation, was arranged. This was followed by subsequent discussion with the ISHLT Nursing, Health Science and Allied Health Council. Evidence and expert opinions regarding key issues were reviewed. A modified nominal group technique was used to reach consensus. Consensus reached included: (1) a minimum of 2 years nursing experience is required for transplant coordinators, nurse managers or advanced practice nurses; (2) a baccalaureate in nursing is the minimum education level required for a transplant coordinator; (3) transplant coordinator-specific certification is recommended; (4) nurse practitioners, clinical nurse specialists and nurse managers should hold at least a master's degree; and (5) strategies to retain transplant nurses include engaging donor call teams, mentoring programs, having flexible hours and offering career advancement support. Future research should focus on the relationships between staffing levels, nurse education and patient outcomes. Delineation of roles and guidelines for education, certification, licensure and staffing levels of transplant nurses are needed to support all nurses working at the fullest extent of their education and licensure. This consensus document provides such recommendations and draws attention to areas for future research. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Myocardial strain abnormalities in fetal congenital heart disease assessed by speckle tracking echocardiography.

PubMed

Germanakis, Ioannis; Matsui, Hikoro; Gardiner, Helena M

2012-01-01

To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiography. We prospectively stored and analyzed 4-chamber loops of 28 fetuses with CHD (median gestation 27 weeks, range 20.9-37.0). The peak longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived original coordinates. Strain values from the first examination were compared with normative data from the same population using ANOVA with post hoc tests and serial examinations described in 14 fetuses. Simple shunt lesions (0.82) and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV strain ratios compared to normal fetuses (1.01; 95% CI 0.97-1.05). Fetuses with hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic coarctation and aortic stenosis, but not in one developing important mitral regurgitation. Increased right ventricular loading in a fetus developing pulmonary regurgitation was associated with increasing RVs. Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses. Copyright © 2012 S. Karger AG, Basel.

Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart.

PubMed

Burmeister, Brian T; Taglieri, Domenico M; Wang, Li; Carnegie, Graeme K

2012-11-23

AKAP-Lbc is a scaffold protein that coordinates cardiac hypertrophic signaling. AKAP-Lbc interacts with Shp2, facilitating its regulation by PKA. AKAP-Lbc integrates PKA and Shp2 signaling in the heart. Under pathological hypertrophic conditions Shp2 is phosphorylated by PKA, and phosphatase activity is inhibited. Inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote pathological cardiac hypertrophy. Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy.

Comprehensive evaluation of lung allograft function in infants after lung and heart-lung transplantation.

PubMed

Hayes, Don; Naguib, Aymen; Kirkby, Stephen; Galantowicz, Mark; McConnell, Patrick I; Baker, Peter B; Kopp, Benjamin T; Lloyd, Eric A; Astor, Todd L

2014-05-01

Limited data exist on methods to evaluate allograft function in infant recipients of lung and heart-lung transplants. At our institution, we developed a procedural protocol in coordination with pediatric anesthesia where infants were sedated to perform infant pulmonary function testing, computed tomography imaging of the chest, and flexible fiberoptic bronchoscopy with transbronchial biopsies. A retrospective review was performed of children aged younger than 1 year who underwent lung or heart-lung transplantation at our institution to assess the effect of this procedural protocol in the evaluation of infant lung allografts. Since 2005, 5 infants have undergone thoracic transplantation (3 heart-lung, 2 lung). At time of transplant, the mean ± standard deviation age was 7.2 ± 2.8 months (range, 3-11 months). Of 24 procedural sessions performed to evaluate lung allografts, 83% (20 of 24) were considered surveillance where the patients were completely asymptomatic. Of the surveillance procedures, 80% were performed as an outpatient, whereas 20% were done as inpatients during the lung or heart-lung transplant post-operative period before discharge home. Sedation was performed with propofol alone (23 of 24) or in addition to ketamine (1 of 24) infusion; mean sedation time was 141 ± 39 minutes (range, 70-214) minutes. Of the 16 outpatient procedures, patients were discharged after 14 (88%) on the same day, and after 2 (12%) were admitted for observation, with 1 being due to transportation issues and the other due to fever during the observation period. A comprehensive procedural protocol to evaluate allograft function in infant lung and heart-lung transplant recipients was performed safely as an outpatient. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

PubMed Central

Andresen, M. C.; Armour, J. A.; Billman, G. E.; Chen, P.‐S.; Foreman, R. D.; Herring, N.; O'Leary, D. S.; Sabbah, H. N.; Schultz, H. D.; Sunagawa, K.; Zucker, I. H.

2016-01-01

Abstract Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various ‘levels’ become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

Neuropeptide action in insects and crustaceans.

PubMed

Mykles, Donald L; Adams, Michael E; Gäde, Gerd; Lange, Angela B; Marco, Heather G; Orchard, Ian

2010-01-01

Physiological processes are regulated by a diverse array of neuropeptides that coordinate organ systems. The neuropeptides, many of which act through G protein-coupled receptors, affect the levels of cyclic nucleotides (cAMP and cGMP) and Ca(2+) in target tissues. In this perspective, their roles in molting, osmoregulation, metabolite utilization, and cardiovascular function are highlighted. In decapod crustaceans, inhibitory neuropeptides (molt-inhibiting hormone and crustacean hyperglycemic hormone) suppress the molting gland through cAMP- and cGMP-mediated signaling. In insects, the complex movements during ecdysis are controlled by ecdysis-triggering hormone and a cascade of downstream neuropeptides. Adipokinetic/hypertrehalosemic/hyperprolinemic hormones mobilize energy stores in response to increased locomotory activity. Crustacean cardioacceleratory (cardioactive) peptide, proctolin, and FMRFamide-related peptides act on the heart, accessory pulsatile organs, and excurrent ostia to control hemolymph distribution to tissues. The osmoregulatory challenge of blood gorging in Rhodnius prolixus requires the coordinated release of serotonin and diuretic and antidiuretic hormones acting on the midgut and Malpighian tubules. These studies illustrate how multiple neuropeptides allow for flexibility in response to physiological challenges.

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care. In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care. Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs.

Joint Force Quarterly. Issue 41, 2nd Quarter, April 2006

DTIC Science & Technology

2006-04-01

crisis . Notably, USSOUTHCOM is the first regional combatant command to incorporate the State Department Office of the Coordinator for Reconstruction...only entered into conflicts in areas that were undergoing some sort of humani- tarian crisis , which has either been a focal point of the war effort or...a critical factor in winning the hearts and minds of the local populace. In these operations, winning the war and solving the humanitarian crisis

Visualizing collaborative electronic health record usage for hospitalized patients with heart failure.

PubMed

Soulakis, Nicholas D; Carson, Matthew B; Lee, Young Ji; Schneider, Daniel H; Skeehan, Connor T; Scholtens, Denise M

2015-03-01

To visualize and describe collaborative electronic health record (EHR) usage for hospitalized patients with heart failure. We identified records of patients with heart failure and all associated healthcare provider record usage through queries of the Northwestern Medicine Enterprise Data Warehouse. We constructed a network by equating access and updates of a patient's EHR to a provider-patient interaction. We then considered shared patient record access as the basis for a second network that we termed the provider collaboration network. We calculated network statistics, the modularity of provider interactions, and provider cliques. We identified 548 patient records accessed by 5113 healthcare providers in 2012. The provider collaboration network had 1504 nodes and 83 998 edges. We identified 7 major provider collaboration modules. Average clique size was 87.9 providers. We used a graph database to demonstrate an ad hoc query of our provider-patient network. Our analysis suggests a large number of healthcare providers across a wide variety of professions access records of patients with heart failure during their hospital stay. This shared record access tends to take place not only in a pairwise manner but also among large groups of providers. EHRs encode valuable interactions, implicitly or explicitly, between patients and providers. Network analysis provided strong evidence of multidisciplinary record access of patients with heart failure across teams of 100+ providers. Further investigation may lead to clearer understanding of how record access information can be used to strategically guide care coordination for patients hospitalized for heart failure. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Regulation of heart rate and rumen temperature in red deer: effects of season and food intake

PubMed Central

Turbill, Christopher; Ruf, Thomas; Mang, Thomas; Arnold, Walter

2012-01-01

SUMMARY Red deer, Cervus elaphus, like other temperate-zone animals, show a large seasonal fluctuation in energy intake and expenditure. Many seasonal phenotypic adjustments are coordinated by endogenous signals entrained to the photoperiod. The cues determining variation in the resting metabolism of ungulates remain equivocal, however, largely because of the confounding effects of food intake and thus the heat increment of feeding. To distinguish endogenous seasonal and environmental effects on metabolism, we subjected 15 female red deer to two feeding treatments, 80% food restriction and low/high protein content, over two winter seasons in a cross-over design experiment. We used rumen-located transmitters to measure heart rate and rumen temperature, which provided indices of metabolism and core body temperature, respectively. Our mixed model (R2=0.85) indicated a residual seasonal effect on mean daily heart rate that was unexplained by the pellet food treatments, activity, body mass or air temperature. In addition to an apparently endogenous down-regulation of heart rate in winter, the deer further reduced heart rate over about 8 days in response to food restriction. We found a strong correlation between rumen temperature and seasonal or periodic variation in heart rate. An effect of lowered rumen (and hence core body) temperature was enhanced during winter, perhaps owing to peripheral cooling, which is known to accompany bouts of hypometabolism. Our experimental results therefore support the hypothesis that a reduction in body temperature is a physiological mechanism employed even by large mammals, like red deer, to reduce their energy expenditure during periods of negative energy balance. PMID:21346124

Multidsciplinary heart failure management and end of life care.

PubMed

Ryder, Mary; Beattie, James M; O'Hanlon, Rory; McDonald, Kenneth

2011-12-01

There has been much improvement in the treatment of heart failure over the past decade through the implementation of a multidisciplinary team approach to disease management focused on optimizing medication, the application of device-based therapy, surgical intervention and in promoting the education of patients and carers in self-management. This multidisciplinary strategy has now been extended to try and improve the care of those with advanced heart failure in the latter phases of the disease trajectory nearing the end of their lives. A growing consensus has emerged in the literature that confirms the need to extend multidisciplinary management beyond the early targets of reducing heart failure-related mortality and morbidity to address the significant care needs of those who decline due to the often inexorable progression of this syndrome. Multidisciplinary management facilitates the development of a comprehensive care plan that is specifically tailored to accommodate the requirements of individual patients and their families and fosters a collaborative approach to care to optimize symptom management, avoid potential treatments conflicts, and to fulfil their supportive care needs. Partnership working between the three principal clinical disciplines of cardiology, specialist palliative care and general practice is central to this process and promotes coordinated care across hospital, hospice and community-based services. Advanced heart failure management has improved over time; however, the incorporation of a multidisciplinary care model appears to offer significant promise in dealing with complex care needs of heart failure patients towards the end of life. Delivery of this practice requires the development of bespoke care structures that are relevant to the spectrum of healthcare service environments.

Optical Electrophysiology in the Developing Heart.

PubMed

Thomas, Kandace; Goudy, Julie; Henley, Trevor; Bressan, Michael

2018-05-11

The heart is the first organ system to form in the embryo. Over the course of development, cardiomyocytes with differing morphogenetic, molecular, and physiological characteristics are specified and differentiate and integrate with one another to assemble a coordinated electromechanical pumping system that can function independently of any external stimulus. As congenital malformation of the heart presents the leading class of birth defects seen in humans, the molecular genetics of heart development have garnered much attention over the last half century. However, understanding how genetic perturbations manifest at the level of the individual cell function remains challenging to investigate. Some of the barriers that have limited our capacity to construct high-resolution, comprehensive models of cardiac physiological maturation are rapidly being removed by advancements in the reagents and instrumentation available for high-speed live imaging. In this review, we briefly introduce the history of imaging approaches for assessing cardiac development, describe some of the reagents and tools required to perform live imaging in the developing heart, and discuss how the combination of modern imaging modalities and physiological probes can be used to scale from subcellular to whole-organ analysis. Through these types of imaging approaches, critical insights into the processes of cardiac physiological development can be directly examined in real-time. Moving forward, the synthesis of modern molecular biology and imaging approaches will open novel avenues to investigate the mechanisms of cardiomyocyte maturation, providing insight into the etiology of congenital heart defects, as well as serving to direct approaches for designing stem-cell or regenerative medicine protocols for clinical application.

What Is New in Heart Failure Management in 2017? Update on ACC/AHA Heart Failure Guidelines.

PubMed

Bozkurt, Biykem

2018-04-17

The goal of this paper is to provide a summary of the new recommendations in the most recent 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. The intent is to provide the background and the supporting evidence for the recommendations and to provide practical guidance for management strategies in treatment of heart failure patients. In the 2017 ACC/AHA/HFSA Focused Update of HF guidelines, important additions include new information on biomarkers, specifically on the topics of the diagnostic, prognostic role of natriuretic peptides in heart failure, and the role of natriuretic peptides in screening in patients high risk for HF and prevention of HF. There are important recommendations for treatment of patients with HF with reduced EF (HFrEF), including the beneficial role of angiotensin receptor blocker and neprilysin inhibition (ARNI) treatment in reducing outcomes including mortality, ivabradine in reducing heart failure hospitalizations in stable HFrEF patients with sinus rhythm and heart rate ≥ 70 bpm despite β-blockers. In patients with HF with preserved EF (HFpEF), though there are no studies demonstrating survival benefit, potential benefit with aldosterone antagonism in reducing HF hospitalizations is noted. In treatment of comorbidities, optimization of blood pressure control to less than 130 mmHg is recommended in hypertensive patients to prevent HF or in patients with hypertension and HFrEF or HFpEF. In addition to recognition on the potential role of treatment of iron deficiency anemia to improve symptoms and functional capacity, caution against use of adaptive servo-ventilation in patients with HFrEF and central sleep apnea and against use of erythropoietin stimulating agents in patients with HFrEF is provided. There are new treatment strategies that are associated with significant improvements in mortality and other outcomes in patients with HF. Successful management of HF requires recognition of indications, contraindications, benefits, safety, and risk of these new therapies. In addition to incorporation of these new treatment strategies, it is critical to focus also on patient education, care coordination, identification of goals of care, monitoring, management of comorbidities, and individualization of therapies. New treatment modalities increase the choices for treatment and provide the opportunity to implement individualized treatment strategies for our patients.

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.

PubMed

Rakov, Helena; Engels, Kathrin; Hönes, Georg Sebastian; Strucksberg, Karl-Heinz; Moeller, Lars Christian; Köhrle, Josef; Zwanziger, Denise; Führer, Dagmar

2016-01-01

Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver. Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue in line with altered functional and metabolic traits of hyper- and hypothyroidism. These data demonstrate that the phenotypes of hypo- and hyperthyroidism differ between male and female mice and indicate that sex is an important modifier of phenotypic manifestations.

Synthesis and Biodistribution of Lipophilic Monocationic Gallium Radiopharmaceuticals Derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: Potential Agents for PET Myocardial Imaging with 68Ga

PubMed Central

Hsiao, Yui-May; Mathias, Carla J.; Wey, Shiaw-Pyng; Fanwick, Phillip E.; Green, Mark A.

2009-01-01

Introduction In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga-radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiologic processes. Methods The lipophilic, monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands, the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-methoxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6− salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates determined in rats following i.v. administration and compared to the biodistribution of [86Rb]rubidium chloride. Results The [Ga(4-MeOsal)2BAPDMEN]+PF6− complex exhibits the expected pseudo-octahedral N4O22− coordination sphere about the Ga3+ center with a trans-disposition of the phenolate oxygen atoms. All five of the 67Ga-radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart at both 1-minute and 2-hours post-injection and very high heart/non-target ratios (heart/blood ratios of 7.6 ± 1.0 and 54 ± 10 at 1-min and 120-min, respectively; heart/liver ratios of 1.8 ± 0.4 and 39 ± 3 at 1-min and 120-min, respectively). Conclusions Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicyaldimines) of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga. PMID:19181267

Myocardial ischaemia and the cardiac nervous system.

PubMed

Armour, J A

1999-01-01

The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some tentative ideas concerning the importance of this nervous system in cardiac disease states with a view to stimulating further interest in neural control of the heart so that appropriate neurocardiological strategies can be devised for the management of heart disease.

GSK3- and PRMT-1–dependent modifications of desmoplakin control desmoplakin–cytoskeleton dynamics

PubMed Central

Albrecht, Lauren V.; Zhang, Lichao; Shabanowitz, Jeffrey; Purevjav, Enkhsaikhan; Towbin, Jeffrey A.; Hunt, Donald F.

2015-01-01

Intermediate filament (IF) attachment to intercellular junctions is required for skin and heart integrity, but how the strength and dynamics of this attachment are modulated during normal and pathological remodeling is poorly understood. We show that glycogen synthase kinase 3 (GSK3) and protein arginine methyltransferase 1 (PRMT-1) cooperate to orchestrate a series of posttranslational modifications on the IF-anchoring protein desmoplakin (DP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion. Front-end electron transfer dissociation mass spectrometry analyses of DP revealed six novel serine phosphorylation sites dependent on GSK3 signaling and four novel arginine methylation sites including R2834, the mutation of which has been associated with arrhythmogenic cardiomyopathy (AC). Inhibition of GSK3 or PRMT-1 or overexpression of the AC-associated mutant R2834H enhanced DP–IF associations and delayed junction assembly. R2834H blocked the GSK3 phosphorylation cascade and reduced DP–GSK3 interactions in cultured keratinocytes and in the hearts of transgenic R2834H DP mice. Interference with this regulatory machinery may contribute to skin and heart diseases. PMID:25733715

Quality of life and coping in patients awaiting heart transplantation.

PubMed

Muirhead, J; Meyerowitz, B E; Leedham, B; Eastburn, T E; Merrill, W H; Frist, W H

1992-01-01

The psychosocial adaptation of patients awaiting heart transplantation has not been defined. Forty-one patients (36 men, 5 women; mean age, 48 years) completed standardized questionnaires before transplantation to assess quality of life, physical symptoms, marital/social adjustment, psychiatric morbidity, coping, and compliance to medical regimens. Also, data were obtained from spouses/partners and the transplantation nurse coordinator. Unlike previously reported findings with patients after transplantation, those awaiting transplantation report moderate dissatisfaction with quality of life. Patients report physical symptoms, functional disabilities, sexual dysfunction, and psychological distress. Nonetheless, reported levels of compliance with the medical regimens and of social support were high, and both patients and spouses/partners provided marital adjustment ratings on the Dyadic Adjustment Scale that were comparable to those of well-adjusted, happily married couples. High levels of coping also were recorded. Having a positive attitude and seeking social support were the most common coping strategies, whereas confrontation, acceptance, and escapism were relatively uncommon. In conclusion, patients awaiting heart transplantation, although dissatisfied with quality of life, maintain positive psychological and social adjustment.

Image-Based Predictive Modeling of Heart Mechanics.

PubMed

Wang, V Y; Nielsen, P M F; Nash, M P

2015-01-01

Personalized biophysical modeling of the heart is a useful approach for noninvasively analyzing and predicting in vivo cardiac mechanics. Three main developments support this style of analysis: state-of-the-art cardiac imaging technologies, modern computational infrastructure, and advanced mathematical modeling techniques. In vivo measurements of cardiac structure and function can be integrated using sophisticated computational methods to investigate mechanisms of myocardial function and dysfunction, and can aid in clinical diagnosis and developing personalized treatment. In this article, we review the state-of-the-art in cardiac imaging modalities, model-based interpretation of 3D images of cardiac structure and function, and recent advances in modeling that allow personalized predictions of heart mechanics. We discuss how using such image-based modeling frameworks can increase the understanding of the fundamental biophysics behind cardiac mechanics, and assist with diagnosis, surgical guidance, and treatment planning. Addressing the challenges in this field will require a coordinated effort from both the clinical-imaging and modeling communities. We also discuss future directions that can be taken to bridge the gap between basic science and clinical translation.

Hatching behavior of eastern long-necked turtles (Chelodina longicollis): The influence of asynchronous environments on embryonic heart rate and phenotype.

PubMed

McGlashan, Jessica K; Loudon, Fiona K; Thompson, Michael B; Spencer, Ricky-John

2015-10-01

Variable temperatures within a nest cause asynchronous development within clutches of freshwater turtle embryos, yet synchronous hatching occurs and is thought to be an important survival strategy for hatchlings. Metabolic compensation and circadian rhythms in heart rates of embryonic turtles indicate the potential of communication between embryos in a nest. Heart rates were used to identify metabolic circadian rhythms in clutches of an Australian freshwater turtle (Chelodina longicollis) and determine whether embryos metabolically compensate and hatch synchronously when incubated in asynchronous environments. The effects of a group environment during incubation on egg development and incubation period were also investigated during the final 3 weeks of development. Chelodina longicollis hatch synchronously and metabolically compensate so that less advanced embryos catch up to more advanced clutch-mates. Heart rates of embryos remained stable from week 4-7 in asynchronous (M=89 bpm) and synchronous (M=92 bpm) groups and declined in the final 2 weeks of incubation (M=72 and 77 bpm). Circadian rhythms were present throughout development and diel heart rates of embryos in asynchronous groups showed less deviation from the mean (M=-0.5 bpm) than synchronous groups (M=-4 bpm). Eggs incubated in groups had a significantly shorter incubation period than eggs incubated individually. Phenotypic traits including size, performance, and growth of all hatchlings were not affected. Egg position within a turtle nest is important for coordinating development throughout incubation and facilitating synchronous hatching. Copyright © 2015 Elsevier Inc. All rights reserved.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Demaerschalk, Bart M; Kleindorfer, Dawn O; Adeoye, Opeolu M; Demchuk, Andrew M; Fugate, Jennifer E; Grotta, James C; Khalessi, Alexander A; Levy, Elad I; Palesch, Yuko Y; Prabhakaran, Shyam; Saposnik, Gustavo; Saver, Jeffrey L; Smith, Eric E

2016-02-01

To critically review and evaluate the science behind individual eligibility criteria (indication/inclusion and contraindications/exclusion criteria) for intravenous recombinant tissue-type plasminogen activator (alteplase) treatment in acute ischemic stroke. This will allow us to better inform stroke providers of quantitative and qualitative risks associated with alteplase administration under selected commonly and uncommonly encountered clinical circumstances and to identify future research priorities concerning these eligibility criteria, which could potentially expand the safe and judicious use of alteplase and improve outcomes after stroke. Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge and, when appropriate, formulated recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on and approved the final version of this document. The document underwent extensive American Heart Association internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. After a review of the current literature, it was clearly evident that the levels of evidence supporting individual exclusion criteria for intravenous alteplase vary widely. Several exclusionary criteria have already undergone extensive scientific study such as the clear benefit of alteplase treatment in elderly stroke patients, those with severe stroke, those with diabetes mellitus and hyperglycemia, and those with minor early ischemic changes evident on computed tomography. Some exclusions such as recent intracranial surgery are likely based on common sense and sound judgment and are unlikely to ever be subjected to a randomized, clinical trial to evaluate safety. Most other contraindications or warnings range somewhere in between. However, the differential impact of each exclusion criterion varies not only with the evidence base behind it but also with the frequency of the exclusion within the stroke population, the probability of coexistence of multiple exclusion factors in a single patient, and the variation in practice among treating clinicians. © 2015 American Heart Association, Inc.

Description of hot debriefings after in-hospital cardiac arrests in an international pediatric quality improvement collaborative.

PubMed

Sweberg, Todd; Sen, Anita I; Mullan, Paul C; Cheng, Adam; Knight, Lynda; Del Castillo, Jimena; Ikeyama, Takanari; Seshadri, Roopa; Hazinski, Mary Fran; Raymond, Tia; Niles, Dana E; Nadkarni, Vinay; Wolfe, Heather

2018-05-22

The American Heart Association recommends debriefing after attempted resuscitation from in-hospital cardiac arrest (IHCA) to improve resuscitation quality and outcomes. This is the first published study detailing the utilization, process and content of hot debriefings after pediatric IHCA. Using prospective data from the Pediatric Resuscitation Quality Collaborative (pediRES-Q), we analyzed data from 227 arrests occurring between February 1, 2016, and August 31, 2017. Hot debriefings, defined as occurring within minutes to hours of IHCA, were evaluated using a modified Team Emergency Assessment Measure framework for qualitative content analysis of debriefing comments. Hot debriefings were performed following 108 of 227 IHCAs (47%). The median interval to debriefing was 130 min (Interquartile range [IQR] 45, 270). Median debriefing duration was 15 min (IQR 10, 20). Physicians facilitated 95% of debriefings, with a median of 9 participants (IQR 7, 11). After multivariate analysis, accounting for hospital site, debriefing frequency was not associated with patient age, gender, race, illness category or unit type. The most frequent positive (plus) comments involved cooperation/coordination (60%), communication (47%) and clinical standards (41%). The most frequent negative (delta) comments involved equipment (46%), cooperation/coordination (45%), and clinical standards (36%). Approximately half of pediatric IHCAs were followed by hot debriefings. Hot debriefings were multi-disciplinary, timely, and often addressed issues of team cooperation/coordination, communication, clinical standards, and equipment. Additional studies are warranted to identify barriers to hot debriefings and to evaluate the impact of these debriefings on patient outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

PubMed

Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

2016-07-15

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Possible influence of solar extreme events and related geomagnetic disturbances on human cardio-vascular state: Results of collaborative Bulgarian-Azerbaijani studies

NASA Astrophysics Data System (ADS)

Dimitrova, S.; Mustafa, F. R.; Stoilova, I.; Babayev, E. S.; Kazimov, E. A.

2009-02-01

This collaborative study is based on the analysis and comparison of results of coordinated experimental investigations conducted in Bulgaria and Azerbaijan for revealing a possible influence of solar activity changes and related geomagnetic activity variations on the human cardio-vascular state. Arterial blood pressure and heart rate of 86 healthy volunteers were measured on working days during a period of comparatively high solar and geomagnetic activity (2799 measurements in autumn 2001 and spring 2002) in Sofia. Daily experimental investigations of parameters of cardio-vascular health state were performed in Azerbaijan with a permanent group of examined persons. Heart rate and electrocardiograms were digitally registered (in total 1532 records) for seven functionally healthy persons on working days and Saturdays, in the Laboratory of Heliobiology at the Medical Center INAM in Baku, from 15.07.2006 to 13.11.2007. Obtained digital recordings were subjected to medical, statistical and spectral analyses. Special attention was paid to effects of solar extreme events, particularly those of November 2001 and December 2006. The statistical method of the analysis of variance (ANOVA) and post hoc analysis were applied to check the significance of the influence of geomagnetic activity on the cardio-vascular parameters under consideration. Results revealed statistically significant increments for the mean systolic and diastolic blood pressure values of the group with geomagnetic activity increase. Arterial blood pressure values started increasing two days prior to geomagnetic storms and kept their high values up to two days after the storms. Heart rate reaction was ambiguous and not significant for healthy persons examined (for both groups) under conditions with geomagnetic activity changes. It is concluded that heart rate for healthy persons at middle latitudes can be considered as a more stable physiological parameter which is not so sensitive to environmental changes while the dynamics of arterial blood pressure reveals a compensatory reaction of the human organism for adaptation.

The China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) retrospective heart failure study design.

PubMed

Yu, Yuan; Zhang, Hongzhao; Li, Xi; Lu, Yuan; Masoudi, Frederick A; Krumholz, Harlan M; Li, Jing

2018-05-10

Heart failure (HF) is a leading cause of hospitalisation in China, which is experiencing a rapid increase in cardiovascular disease prevalence. Yet, little is known about current burden of disease, quality of care and treatment outcomes of HF in China. The objective of this paper is to describe the study methodology, data collection and abstraction, and progress to date of the China Patient-centered Evaluative Assessment of Cardiac Events 5 Retrospective Heart Failure Study (China PEACE 5r-HF). The China PEACE 5r-HF Study will examine a nationally representative sample of more than 10 000 patient records hospitalised for HF in 2015 in China. The study is a retrospective cohort study. Patients have been selected using a two-stage sampling design stratified by economic-geographical regions. We will collect patient characteristics, diagnostic testing, treatments and in-hospital outcomes, including death and complications, and charges of hospitalisation. Data quality will be monitored by a central coordinating centre and will address case ascertainment, data abstraction and data management. As of October 2017, we have sampled 15 538 medical records from 189 hospitals, and have received 15 057 (96.9%) of these for data collection, and completed data abstraction and quality control on 7971. The Central Ethics Committee at the Chinese National Center for Cardiovascular Diseases approved the study. All collaborating hospitals accepted central ethics committee approval with the exception of 15 hospitals, which obtained local approval by internal ethics committees. Findings will be disseminated in future peer-reviewed papers and will serve as a foundation for improving the care for HF in China. NCT02877914. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.

PubMed

Lam, Maggie P Y; Wang, Ding; Lau, Edward; Liem, David A; Kim, Allen K; Ng, Dominic C M; Liang, Xiangbo; Bleakley, Brian J; Liu, Chenguang; Tabaraki, Jason D; Cadeiras, Martin; Wang, Yibin; Deng, Mario C; Ping, Peipei

2014-04-01

Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide (2H2O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of β-adrenergic-induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to large-scale biomolecular investigations of human disease mechanisms with a temporal perspective.

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

PubMed Central

Lam, Maggie P.Y.; Wang, Ding; Lau, Edward; Liem, David A.; Kim, Allen K.; Ng, Dominic C.M.; Liang, Xiangbo; Bleakley, Brian J.; Liu, Chenguang; Tabaraki, Jason D.; Cadeiras, Martin; Wang, Yibin; Deng, Mario C.; Ping, Peipei

2014-01-01

Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide (2H2O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of β-adrenergic–induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to large-scale biomolecular investigations of human disease mechanisms with a temporal perspective. PMID:24614109

Left ventricular volume analysis as a basic tool to describe cardiac function.

PubMed

Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

2018-03-01

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway.

PubMed

Carnegie, Graeme K; Soughayer, Joseph; Smith, F Donelson; Pedroja, Benjamin S; Zhang, Fang; Diviani, Dario; Bristow, Michael R; Kunkel, Maya T; Newton, Alexandra C; Langeberg, Lorene K; Scott, John D

2008-10-24

Elevated catecholamines in the heart evoke transcriptional activation of the Myocyte Enhancer Factor (MEF) pathway to induce a cellular response known as pathological myocardial hypertrophy. We have discovered that the A-Kinase Anchoring Protein (AKAP)-Lbc is upregulated in hypertrophic cardiomyocytes. It coordinates activation and movement of signaling proteins that initiate MEF2-mediated transcriptional reprogramming events. Live-cell imaging, fluorescent kinase activity reporters, and RNA interference techniques show that AKAP-Lbc couples activation of protein kinase D (PKD) with the phosphorylation-dependent nuclear export of the class II histone deacetylase HDAC5. These studies uncover a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac myocytes toward a pathophysiological outcome.

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

PubMed Central

Schulz, Rainer; Görge, Philipp Maximilian; Görbe, Anikó; Ferdinandy, Péter; Lampe, Paul D.; Leybaert, Luc

2015-01-01

Connexins are widely distributed proteins in the body that are crucially important for heart and brain function. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localisation at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodelling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injury as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissue following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection. PMID:26073311

[Organization of clinical research: in a large scale department for cardiothoracic surgery].

PubMed

Sarikouch, S; Schilling, T; Haverich, A

2010-04-01

Translation of basic research results into routine patient care is delayed in parts by lack of institutionalization in clinical research. In this article the research structure and organization of our Department of Cardiac, Thoracic, Transplantation and Vascular Surgery are described.Basic research, separately directed, is accomplished in the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) and within the scope of the Excellence cluster "REBIRTH--from Regenerative Biology to Reconstructive Therapy".Clinical research is directed by heads of the subdepartments of our institution (valve and coronary surgery, aortic surgery, surgical electrophysiology, vascular surgery, thoracic surgery, cardiac assist systems, thoracic transplantation, intensive care and pediatric heart surgery).A separate subdepartment for clinical research is responsible for study coordination and accompanies clinical studies from study design and patient screening to publication. This subdepartment also serves as a constant contact to sponsors and superordinated research organizations within the Hannover Medical School.

Expert Comment: Is Medication Titration in Heart Failure too Complex?

PubMed Central

Hickey, Annabel

2017-01-01

Abstract Large-scale randomised controlled trials (RCTs) have demonstrated that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers decrease mortality and hospitalisation in patients with heart failure (HF) associated with a reduced left ventricular ejection fraction. This has led to high prescription rates; however, these drugs are generally prescribed at much lower doses than the doses achieved in the RCTs. A number of strategies have been evaluated to improve medication titration in HF, including forced medication up-titration protocols, point-of-care decision support and extended scope of clinical practice for nurses and pharmacists. Most successful strategies have been multifaceted and have adapted existing multidisciplinary models of care. Furthermore, given the central role of general practitioners in long-term monitoring and care coordination in HF patients, these strategies should engage with primary care to facilitate the transition between the acute and primary healthcare sectors. PMID:28785472

Sequential Notch activation regulates ventricular chamber development

PubMed Central

D'Amato, Gaetano; Luxán, Guillermo; del Monte-Nieto, Gonzalo; Martínez-Poveda, Beatriz; Torroja, Carlos; Walter, Wencke; Bochter, Matthew S.; Benedito, Rui; Cole, Susan; Martinez, Fernando; Hadjantonakis, Anna-Katerina; Uemura, Akiyoshi; Jiménez-Borreguero, Luis J.; de la Pompa, José Luis

2016-01-01

Ventricular chambers are essential for the rhythmic contraction and relaxation occurring in every heartbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is poorly understood. We show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation, and later coordinates ventricular patterning and compaction with coronary vessel development to generate the mature chamber, through a temporal sequence of ligand signalling determined by the glycosyltransferase manic fringe (MFng). Early endocardial expression of MFng promotes Dll4–Notch1 signalling, which induces trabeculation in the developing ventricle. Ventricular maturation and compaction require MFng and Dll4 downregulation in the endocardium, which allows myocardial Jag1 and Jag2 signalling to Notch1 in this tissue. Perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. PMID:26641715

Learning distance function for regression-based 4D pulmonary trunk model reconstruction estimated from sparse MRI data

NASA Astrophysics Data System (ADS)

Vitanovski, Dime; Tsymbal, Alexey; Ionasec, Razvan; Georgescu, Bogdan; Zhou, Shaohua K.; Hornegger, Joachim; Comaniciu, Dorin

2011-03-01

Congenital heart defect (CHD) is the most common birth defect and a frequent cause of death for children. Tetralogy of Fallot (ToF) is the most often occurring CHD which affects in particular the pulmonary valve and trunk. Emerging interventional methods enable percutaneous pulmonary valve implantation, which constitute an alternative to open heart surgery. While minimal invasive methods become common practice, imaging and non-invasive assessment tools become crucial components in the clinical setting. Cardiac computed tomography (CT) and cardiac magnetic resonance imaging (cMRI) are techniques with complementary properties and ability to acquire multiple non-invasive and accurate scans required for advance evaluation and therapy planning. In contrary to CT which covers the full 4D information over the cardiac cycle, cMRI often acquires partial information, for example only one 3D scan of the whole heart in the end-diastolic phase and two 2D planes (long and short axes) over the whole cardiac cycle. The data acquired in this way is called sparse cMRI. In this paper, we propose a regression-based approach for the reconstruction of the full 4D pulmonary trunk model from sparse MRI. The reconstruction approach is based on learning a distance function between the sparse MRI which needs to be completed and the 4D CT data with the full information used as the training set. The distance is based on the intrinsic Random Forest similarity which is learnt for the corresponding regression problem of predicting coordinates of unseen mesh points. Extensive experiments performed on 80 cardiac CT and MR sequences demonstrated the average speed of 10 seconds and accuracy of 0.1053mm mean absolute error for the proposed approach. Using the case retrieval workflow and local nearest neighbour regression with the learnt distance function appears to be competitive with respect to "black box" regression with immediate prediction of coordinates, while providing transparency to the predictions made.

The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure.

PubMed

de Boer, Rudolf A; Cao, Qi; Postmus, Douwe; Damman, Kevin; Voors, Adriaan A; Jaarsma, Tiny; van Veldhuisen, Dirk J; Arnold, William D; Hillege, Hans L; Silljé, Herman H W

2013-04-01

This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF). Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment. Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model. HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Mechanical circulatory support and heart transplantation in the Asia Pacific region.

PubMed

Sivathasan, Cumaraswamy; Lim, Choon Pin; Kerk, Ka Lee; Sim, David K L; Mehra, Mandeep R

2017-01-01

Globalization has resulted in epidemiologic transition in developing countries from infectious disease and nutritional deficiencies to non-communicable diseases. Epidemiologic data on heart failure (HF), particularly advanced HF therapy, in Asia are increasingly becoming available, although they remain sparse. Heart transplantation for advanced stage HF remains very low in Asia-approximately 0.075 heart transplants per 1 million population. North America, which comprises 7.5% of the world population, accounted for 55.8% of transplants recorded in the 2012 International Society for Heart and Lung Transplantation (ISHLT) Registry, whereas Asia, with 62.5% of the world population, accounted for 5.7% of transplants. There is also lack of reporting from heart transplant centers in Asia to the ISHLT Registry. Most transplant programs in Asia are in economically stable South East Asian countries, whereas in other parts of developing countries, the cost and health care infrastructures remain prohibitive for the development of these programs. Multi-cultural and racial factors, religious beliefs, and diverse traditions of many centuries have resulted in reluctance to organ donation. Mechanical circulatory support (MCS) is emerging as a viable alternative to transplantation, but despite technical capabilities, limitations in embracing MCS in Asia exist. Discrepant practices in the reimbursement of costly MCS therapy have led to differences in the availability of these devices to patients in the region. The HeartMate II (St. Jude Medical, Inc, St. Paul, MN) left ventricular assist device is currently the most widely used durable device in Asia, whereas the HeartWare HVAD (HeartWare, Inc, Framingham, MA) is used most often in Australia. By September 9, 2015, 341 HeartMate implants (293 as bridge to transplant and 48 as destination therapy) had been performed, of which 180 implants were in Japan. The overall 4-year survival is 88%. The longest duration of support is 6.5 years. By the end of 2015, 243 HeartWare HVADs had been implanted in Asia Pacific. There is a need for focused efforts at improving the reporting of data and intensifying health policy within the region to advocate organ transplantation. Individual governments need to take national responsibility to fulfill organ donation and transplantation needs of their populations. International collaboratives, coordinated by societies such as the ISHLT, will be essential in moving this field forward in Asia Pacific. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Distinct mechanisms determine organ left-right asymmetry patterning in an uncoupled way.

PubMed

Huang, Sizhou; Xu, Wenming; Su, Bingyin; Luo, Lingfei

2014-03-01

Disruption of Nodal in the lateral plate mesoderm (LPM) usually leads to left-right (LR) patterning defects in multiple organs. However, whether the LR patterning of organs is always regulated in a coupled way has largely not yet been elucidated. In addition, whether other crucial regulators exist in the LPM that coordinate with Nodal in regulating organ LR patterning is also undetermined. In this paper, after briefly summarizing the common process of LR patterning, the most puzzling question regarding the initiation of asymmetry is considered and the divergent mechanisms underlying the uncoupled LR patterning in different organs are discussed. On the basis of cases in which different organ LR patterning is determined in an uncoupled way via an independent mechanism or at a different time, we propose that there are other critical factors in the LPM that coordinate with Nodal to regulate heart LR asymmetry patterning during early LR patterning. © 2014 WILEY Periodicals, Inc.

Deployment of lean six sigma in care coordination: an improved discharge process.

PubMed

Breslin, Susan Ellen; Hamilton, Karen Marie; Paynter, Jacquelyn

2014-01-01

This article presents a quality improvement project to reduce readmissions in the Medicare population related to heart failure, acute myocardial infarction, and pneumonia. The article describes a systematic approach to the discharge process aimed at improving transitions of care from hospital to post-acute care, utilizing Lean Six Sigma methodology. Inpatient acute care hospital. A coordinated discharge process, which includes postdischarge follow-up, can reduce avoidable readmissions. Implications for The quality improvement project demonstrated the significant role case management plays in preventing costly readmissions and improving outcomes for patients through better transitions of care from the hospital to the community. By utilizing Lean Six Sigma methodology, hospitals can focus on eliminating waste in their current processes and build more sustainable improvements to deliver a safe, quality, discharge process for their patients. Case managers are leading this effort to improve care transitions and assure a smoother transition into the community postdischarge..

Use of donor bladder tissues for in vitro research.

PubMed

Garthwaite, Mary; Hinley, Jennifer; Cross, William; Warwick, Ruth M; Ambrose, Anita; Hardaker, Henry; Eardley, Ian; Southgate, Jennifer

2014-01-01

To evaluate deceased non-heart beating (DNHB) donors and deceased heart beating (DHB) brain-stem dead donors, as sources of viable urological tissue for use in biomedical research. To identify sources of viable human bladder tissue as an essential resource for cell biological research aimed at understanding human diseases of the bladder and for developing new tissue engineering and regenerative medicine strategies for bladder reconstruction. Typically, normal human urinary tract tissue is obtained from adult or paediatric surgical patients with benign urological conditions, but few surgical procedures yield useful quantities of healthy bladder tissue for research. Research ethics committee approval was obtained for collection of donor bladder tissue. Consent for DHB donors was undertaken by the Donor Transplant Coordinators. Tissue Donor Coordinators were responsible for consent for DNHB donors and the retrieval of bladders was coordinated through the National Blood Service Tissue Banking Service. All retrievals were performed by practicing urologists and care was taken to maintain sterility and to minimise bacterial contamination. Two bladders were retrieved from DNHB donors and four were retrieved from DHB donors. By histology, DNHB donor bladder tissue exhibited marked urothelial tissue damage and necrosis, with major loss or absence of urothelium. No cell cultures could be established from these specimens, as the urothelial cells were not viable in primary culture. Bladder urothelium from DHB donors was intact, but showed some damage, including loss of superficial cells and variable separation from the basement membrane. All four DHB bladder specimens yielded viable urothelial cells that attached in primary culture, but cell growth was slow to establish and cultures showed a limited capacity to form a functional barrier epithelium and a propensity to senesce early. We have shown that normal human bladder urothelial cell cultures can be established and serially propagated from DHB donor bladders. However, our study suggests that rapid post-mortem changes to the bladder affect the quality and viability of the urothelium, rendering tissue from DNHB donors an inadequate source for urothelial cell culture. Our experience is that whereas patients are willing to donate surgical tissue for research, there is a barrier to obtaining consent from next of kin for retrieved tissues to be used for research purposes. © 2013 The Authors. BJU International © 2013 BJU International.

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning

PubMed Central

Azarov, Ivan; Wang, Ling; Rose, Jason J.; Xu, Qinzi; Huang, Xueyin N.; Belanger, Andrea; Wang, Ying; Guo, Lanping; Liu, Chen; Ucer, Kamil B.; McTiernan, Charles F.; O’Donnell, Christopher P.; Shiva, Sruti; Tejero, Jesús; Kim-Shapiro, Daniel B.; Gladwin, Mark T.

2016-01-01

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, with no available antidotal therapy. We introduce a potential treatment paradigm for CO poisoning, based on near-irreversible binding of CO by an engineered human neuroglobin (Ngb). Ngb is a six-coordinate hemoprotein, with the heme iron coordinated by two histidine residues. We mutated the distal histidine to glutamine (H64Q) and substituted three surface cysteines with less reactive amino acids to form a five-coordinate heme protein (Ngb-H64Q-CCC). This molecule exhibited an unusually high affinity for gaseous ligands, with a P50 value for oxygen of 0.015 mmHg. Ngb-H64Q-CCC bound CO about 500 times more strongly than did hemoglobin. Incubation of Ngb-H64Q-CCC with 100% CO-saturated hemoglobin, either cell-free or encapsulated in human red blood cells, reduced the half-life of carboxy-hemoglobin to 0.11 and 0.41 minutes, respectively, from a value that is ≥ 200 minutes when the hemoglobin or cells are only exposed to air. Infusions of Ngb-H64Q-CCC to CO-poisoned mice enhanced CO removal from red blood cells, restored heart rate and blood pressure, increased survival, and were followed by rapid renal elimination of CO-bound Ngb-H64Q-CCC. Heme-based scavenger molecules with very high CO binding affinity such as our mutant five-coordinate Ngb are potential antidotes for CO poisoning by virtue of their ability to bind and eliminate CO. PMID:27928027

Reciprocal transcriptional regulation of metabolic and signaling pathways correlates with disease severity in heart failure.

PubMed

Barth, Andreas S; Kumordzie, Ami; Frangakis, Constantine; Margulies, Kenneth B; Cappola, Thomas P; Tomaselli, Gordon F

2011-10-01

Systolic heart failure (HF) is a complex systemic syndrome that can result from a wide variety of clinical conditions and gene mutations. Despite phenotypic similarities, characterized by ventricular dilatation and reduced contractility, the extent of common and divergent gene expression between different forms of HF remains a matter of intense debate. Using a meta-analysis of 28 experimental (mouse, rat, dog) and human HF microarray studies, we demonstrate that gene expression changes are characterized by a coordinated and reciprocal regulation of major metabolic and signaling pathways. In response to a wide variety of stressors in animal models of HF, including ischemia, pressure overload, tachypacing, chronic isoproterenol infusion, Chagas disease, and transgenic mouse models, major metabolic pathways are invariably downregulated, whereas cell signaling pathways are upregulated. In contrast to this uniform transcriptional pattern that recapitulates a fetal gene expression program in experimental animal models of HF, human HF microarray studies displayed a greater heterogeneity, with some studies even showing upregulation of metabolic and downregulation of signaling pathways in end-stage human hearts. These discrepant results between animal and human studies are due to a number of factors, prominently cardiac disease and variable exposure to cold cardioplegic solution in nonfailing human samples, which can downregulate transcripts involved in oxidative phosphorylation (OXPHOS), thus mimicking gene expression patterns observed in failing samples. Additionally, β-blockers and ACE inhibitor use in end-stage human HF was associated with higher levels of myocardial OXPHOS transcripts, thus partially reversing the fetal gene expression pattern. In human failing samples, downregulation of metabolism was associated with hemodynamic markers of disease severity. Irrespective of the etiology, gene expression in failing myocardium is characterized by downregulation of metabolic transcripts and concomitant upregulation of cell signaling pathways. Gene expression changes along this metabolic-signaling axis in mammalian myocardium are a consistent feature in the heterogeneous transcriptional response observed in phenotypically similar models of HF.

Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats.

PubMed

Ghule, Arvindkumar E; Kulkarni, Chetan P; Bodhankar, Subhash L; Pandit, Vijaya A

2009-12-01

Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions. The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats. Albino male Wistar rats (250-300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9-18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician. A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]). Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart.

Maintaining evaluation designs in long term community based health promotion programmes: Heartbeat Wales case study.

PubMed Central

Nutbeam, D; Smith, C; Murphy, S; Catford, J

1993-01-01

STUDY OBJECTIVE--To examine the difficulties of developing and maintaining outcome evaluation designs in long term, community based health promotion programmes. DESIGN--Semistructured interviews of health promotion managers. SETTING--Wales and two reference health regions in England. PARTICIPANTS--Nine health promotion managers in Wales and 18 in England. MEASUREMENTS AND MAIN RESULTS--Information on selected heart health promotion activity undertaken or coordinated by health authorities from 1985-90 was collected. The Heartbeat Wales coronary heart disease prevention programme was set up in 1985, and a research and evaluation strategy was established to complement the intervention. A substantial increase in the budget occurred over the period. In the reference health regions in England this initiative was noted and rapidly taken up, thus compromising their use as control areas. CONCLUSION--Information on large scale, community based health promotion programmes can disseminate quickly and interfere with classic intervention/evaluation control designs through contamination. Alternative experimental designs for assessing the effectiveness of long term intervention programmes need to be considered. These should not rely solely on the use of reference populations, but should balance the measurement of outcome with an assessment of the process of change in communities. The development and use of intervention exposure measures together with well structured and comprehensive process evaluation in both the intervention and reference areas is recommended. PMID:8326270

Exergames for Physical Education Courses: Physical, Social, and Cognitive Benefits.

PubMed

Staiano, Amanda E; Calvert, Sandra L

2011-06-01

Digital games combining exercise with game play, known as exergames, can improve youths' health status and provide social and academic benefits. Exergame play increases caloric expenditure, heart rate, and coordination. Psychosocial and cognitive impacts of exergame play may include increased self-esteem, social interaction, motivation, attention, and visual-spatial skills. This article summarizes the literature on exergames, with a special emphasis on physical education courses and the potential of exergames to improve students' physical health, as well as transfer effects that may benefit related physical, social, and academic outcomes.

Exergames for Physical Education Courses: Physical, Social, and Cognitive Benefits

PubMed Central

Staiano, Amanda E.; Calvert, Sandra L.

2012-01-01

Digital games combining exercise with game play, known as exergames, can improve youths’ health status and provide social and academic benefits. Exergame play increases caloric expenditure, heart rate, and coordination. Psychosocial and cognitive impacts of exergame play may include increased self-esteem, social interaction, motivation, attention, and visual–spatial skills. This article summarizes the literature on exergames, with a special emphasis on physical education courses and the potential of exergames to improve students’ physical health, as well as transfer effects that may benefit related physical, social, and academic outcomes. PMID:22563349

Experiences and Outcomes of Transition from Pediatric to Adult Health Care Services for Young People with Congenital Heart Disease: A Systematic Review.

PubMed

Heery, Emily; Sheehan, Aisling M; While, Alison E; Coyne, Imelda

2015-01-01

This review synthesizes the empirical literature on outcomes and experiences of transfer and transition from pediatric to adult care for young people with congenital heart disease. A systematic review of papers published between January 2001 and May 2013 that examined outcomes or experiences of transfer and transition among young people with congenital heart disease was conducted. Data were extracted by two independent reviewers with the outcomes data combined using narrative synthesis and the experiences data integrated using thematic synthesis. Thirteen papers were included in the review: six reported outcomes following transfer, six reported experiences of transfer and transition, and one reported both outcomes and experiences. The review data indicate that high proportions of young people were lost to follow-up or experienced long gaps in care after leaving pediatric cardiology. Factors that protected against loss to follow-up or lapse in care included: beliefs that specialized adult care was necessary; poorer health status; attendance at pediatric appointments without parents; and pediatric referral to an adult congenital heart disease center. Data on experiences highlighted that many young people were unconcerned about transition, but lacked knowledge about their condition and were insufficiently prepared for transfer. In terms of adult services, many young people desired continuity in the quality of care, youth-oriented facilities, a personalized approach, and for their parents to remain involved in their care, but in a secondary, supportive capacity. In conclusion, the high proportions of young people lost to follow-up highlight the need for formal transition programs, which ensure a planned and coordinated transfer. Patients with congenital heart disease need education throughout adolescence about the implications of their condition, the differences between pediatric and adult services, and self-care management. © 2015 Wiley Periodicals, Inc.

Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

PubMed

Inoue, Takahiro; Kobirumaki-Shimozawa, Fuyu; Kagemoto, Tatsuya; Fujii, Teruyuki; Terui, Takako; Kusakari, Yoichiro; Hongo, Kenichi; Morimoto, Sachio; Ohtsuki, Iwao; Hashimoto, Kazuhiro; Fukuda, Norio

2013-10-01

It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation. © 2013.

Three-dimensional quantification of cardiac surface motion: a newly developed three-dimensional digital motion-capture and reconstruction system for beating heart surgery.

PubMed

Watanabe, Toshiki; Omata, Sadao; Odamura, Motoki; Okada, Masahumi; Nakamura, Yoshihiko; Yokoyama, Hitoshi

2006-11-01

This study aimed to evaluate our newly developed 3-dimensional digital motion-capture and reconstruction system in an animal experiment setting and to characterize quantitatively the three regional cardiac surface motions, in the left anterior descending artery, right coronary artery, and left circumflex artery, before and after stabilization using a stabilizer. Six pigs underwent a full sternotomy. Three tiny metallic markers (diameter 2 mm) coated with a reflective material were attached on three regional cardiac surfaces (left anterior descending, right coronary, and left circumflex coronary artery regions). These markers were captured by two high-speed digital video cameras (955 frames per second) as 2-dimensional coordinates and reconstructed to 3-dimensional data points (about 480 xyz-position data per second) by a newly developed computer program. The remaining motion after stabilization ranged from 0.4 to 1.01 mm at the left anterior descending, 0.91 to 1.52 mm at the right coronary artery, and 0.53 to 1.14 mm at the left circumflex regions. Significant differences before and after stabilization were evaluated in maximum moving velocity (left anterior descending 456.7 +/- 178.7 vs 306.5 +/- 207.4 mm/s; right coronary artery 574.9 +/- 161.7 vs 446.9 +/- 170.7 mm/s; left circumflex 578.7 +/- 226.7 vs 398.9 +/- 192.6 mm/s; P < .0001) and maximum acceleration (left anterior descending 238.8 +/- 137.4 vs 169.4 +/- 132.7 m/s2; right coronary artery 315.0 +/- 123.9 vs 242.9 +/- 120.6 m/s2; left circumflex 307.9 +/- 151.0 vs 217.2 +/- 132.3 m/s2; P < .0001). This system is useful for a precise quantification of the heart surface movement. This helps us better understand the complexity of the heart, its motion, and the need for developing a better stabilizer for beating heart surgery.

Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection.

PubMed

Teutsch, Christine; Kondo, Richard P; Dederko, Dorothy A; Chrast, Jacqueline; Chien, Kenneth R; Giles, Wayne R

2007-03-01

Regional differences in repolarizing K(+) current densities and expression levels of their molecular components are important for coordinating the pattern of electrical excitation and repolarization of the heart. The small size of hearts from mice may obscure these interventricular and/or transmural expression differences of K(+) channels. We have examined this possibility in adult mouse ventricle using a technology that provides very high spatial resolution of tissue collection. Conventional manual dissection and laser capture microdissection (LCM) were utilized to dissect tissue from distinct ventricular regions. RNA was isolated from epicardial, mid-myocardial and endocardial layers of both the right and left ventricles. Real-time RT-PCR was used to quantify the transcript expression in these different regions. LCM revealed significant interventricular and transmural gradients for both Kv4.2 and the alpha-subunit of KChIP2. The expression profile of a second K(+) channel transcript, Kir2.1, which is responsible for the inwardly rectifying K(+) current I(k1), showed no interventricular or transmural gradients and therefore served as a negative control. Our findings are in contrast to previous reports of a relatively uniform left ventricular transmural pattern of expression of Kv4.2, Kv4.3 and KChIP2 in adult mouse heart, which appear to be different than that in larger mammals. Specifically, our results demonstrate significant epi- to endocardial differences in the patterns of expression of both Kv4.2 and KChIP2.

Potential clinical relevance of the 'little brain' on the mammalian heart.

PubMed

Armour, J A

2008-02-01

It is hypothesized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This 'little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue.

IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload

PubMed Central

Sbroggiò, Mauro; Carnevale, Daniela; Bertero, Alessandro; Cifelli, Giuseppe; De Blasio, Emanuele; Mascio, Giada; Hirsch, Emilio; Bahou, Wadie F.; Turco, Emilia; Silengo, Lorenzo; Brancaccio, Mara; Lembo, Giuseppe; Tarone, Guido

2011-01-01

Aims The Raf-MEK1/2-ERK1/2 (ERK1/2—extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements in coordinating signalling molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold for the ERK1/2 cascade, in heart function and remodelling in response to pressure overload. Methods and results IQGAP1-null mice have unaltered basal heart function. When subjected to pressure overload, IQGAP1-null mice initially develop a compensatory hypertrophy indistinguishable from that of wild-type (WT) mice. However, upon a prolonged stimulus, the hypertrophic response develops towards a thinning of left ventricular walls, chamber dilation, and a decrease in contractility, in an accelerated fashion compared with WT mice. This unfavourable cardiac remodelling is characterized by blunted reactivation of the foetal gene programme, impaired cardiomyocyte hypertrophy, and increased cardiomyocyte apoptosis. Analysis of signalling pathways revealed two temporally distinct waves of both ERK1/2 and AKT phosphorylation peaking, respectively, at 10 min and 4 days after aortic banding in WT hearts. IQGAP1-null mice show strongly impaired phosphorylation of MEK1/2-ERK1/2 and AKT following 4 days of pressure overload, but normal activation of these kinases after 10 min. Pull-down experiments indicated that IQGAP1 is able to bind the three components of the ERK cascade, namely c-Raf, MEK1/2, and ERK1/2, as well as AKT in the heart. Conclusion These data demonstrate, for the first time, a key role for the scaffold protein IQGAP1 in integrating hypertrophy and survival signals in the heart and regulating long-term left ventricle remodelling upon pressure overload. PMID:21493702

Computational optogenetics: A novel continuum framework for the photoelectrochemistry of living systems

NASA Astrophysics Data System (ADS)

Wong, Jonathan; Abilez, Oscar J.; Kuhl, Ellen

2012-06-01

Electrical stimulation is currently the gold standard treatment for heart rhythm disorders. However, electrical pacing is associated with technical limitations and unavoidable potential complications. Recent developments now enable the stimulation of mammalian cells with light using a novel technology known as optogenetics. The optical stimulation of genetically engineered cells has significantly changed our understanding of electrically excitable tissues, paving the way towards controlling heart rhythm disorders by means of photostimulation. Controlling these disorders, in turn, restores coordinated force generation to avoid sudden cardiac death. Here, we report a novel continuum framework for the photoelectrochemistry of living systems that allows us to decipher the mechanisms by which this technology regulates the electrical and mechanical function of the heart. Using a modular multiscale approach, we introduce a non-selective cation channel, channelrhodopsin-2, into a conventional cardiac muscle cell model via an additional photocurrent governed by a light-sensitive gating variable. Upon optical stimulation, this channel opens and allows sodium ions to enter the cell, inducing electrical activation. In side-by-side comparisons with conventional heart muscle cells, we show that photostimulation directly increases the sodium concentration, which indirectly decreases the potassium concentration in the cell, while all other characteristics of the cell remain virtually unchanged. We integrate our model cells into a continuum model for excitable tissue using a nonlinear parabolic second-order partial differential equation, which we discretize in time using finite differences and in space using finite elements. To illustrate the potential of this computational model, we virtually inject our photosensitive cells into different locations of a human heart, and explore its activation sequences upon photostimulation. Our computational optogenetics tool box allows us to virtually probe landscapes of process parameters, and to identify optimal photostimulation sequences with the goal to pace human hearts with light and, ultimately, to restore mechanical function.

Measurement and reconstruction of the leaflet geometry for a pericardial artificial heart valve.

PubMed

Jiang, Hongjun; Campbell, Gord; Xi, Fengfeng

2005-03-01

This paper describes the measurement and reconstruction of the leaflet geometry for a pericardial heart valve. Tasks involved include mapping the leaflet geometries by laser digitizing and reconstructing the 3D freeform leaflet surface based on a laser scanned profile. The challenge is to design a prosthetic valve that maximizes the benefits offered to the recipient as compared to the normally operating naturally-occurring valve. This research was prompted by the fact that artificial heart valve bioprostheses do not provide long life durability comparable to the natural heart valve, together with the anticipated benefits associated with defining the valve geometries, especially the leaflet geometries for the bioprosthetic and human valves, in order to create a replicate valve fabricated from synthetic materials. Our method applies the concept of reverse engineering in order to reconstruct the freeform surface geometry. A Brown & Shape coordinate measuring machine (CMM) equipped with a HyMARC laser-digitizing system was used to measure the leaflet profiles of a Baxter Carpentier-Edwards pericardial heart valve. The computer software, Polyworks was used to pre-process the raw data obtained from the scanning, which included merging images, eliminating duplicate points, and adding interpolated points. Three methods, creating a mesh model from cloud points, creating a freeform surface from cloud points, and generating a freeform surface by B-splines are presented in this paper to reconstruct the freeform leaflet surface. The mesh model created using Polyworks can be used for rapid prototyping and visualization. To fit a freeform surface to cloud points is straightforward but the rendering of a smooth surface is usually unpredictable. A surface fitted by a group of B-splines fitted to cloud points was found to be much smoother. This method offers the possibility of manually adjusting the surface curvature, locally. However, the process is complex and requires additional manipulation. Finally, this paper presents a reverse engineered design for the pericardial heart valve which contains three identical leaflets with reconstructed geometry.

Computational Optogenetics: A Novel Continuum Framework for the Photoelectrochemistry of Living Systems.

PubMed

Wong, Jonathan; Abilez, Oscar J; Kuhl, Ellen

2012-06-01

Electrical stimulation is currently the gold standard treatment for heart rhythm disorders. However, electrical pacing is associated with technical limitations and unavoidable potential complications. Recent developments now enable the stimulation of mammalian cells with light using a novel technology known as optogenetics. The optical stimulation of genetically engineered cells has significantly changed our understanding of electrically excitable tissues, paving the way towards controlling heart rhythm disorders by means of photostimulation. Controlling these disorders, in turn, restores coordinated force generation to avoid sudden cardiac death. Here, we report a novel continuum framework for the photoelectrochemistry of living systems that allows us to decipher the mechanisms by which this technology regulates the electrical and mechanical function of the heart. Using a modular multiscale approach, we introduce a non-selective cation channel, channelrhodopsin-2, into a conventional cardiac muscle cell model via an additional photocurrent governed by a light-sensitive gating variable. Upon optical stimulation, this channel opens and allows sodium ions to enter the cell, inducing electrical activation. In side-by-side comparisons with conventional heart muscle cells, we show that photostimulation directly increases the sodium concentration, which indirectly decreases the potassium concentration in the cell, while all other characteristics of the cell remain virtually unchanged. We integrate our model cells into a continuum model for excitable tissue using a nonlinear parabolic second order partial differential equation, which we discretize in time using finite differences and in space using finite elements. To illustrate the potential of this computational model, we virtually inject our photosensitive cells into different locations of a human heart, and explore its activation sequences upon photostimulation. Our computational optogenetics tool box allows us to virtually probe landscapes of process parameters, and to identify optimal photostimulation sequences with the goal to pace human hearts with light and, ultimately, to restore mechanical function.

Meeting the challenges of chronic illness: a nurse-led collaborative community care program in Thailand.

PubMed

Sindhu, Siriorn; Pholpet, Chennet; Puttapitukpol, Somjai

2010-01-01

Chronic illness is of concern to health care systems globally. Although a significant evidence base supports the concept of nurse-led interventions, less data is available to address unique features of health care systems in the developing world. The purpose of this study aimed to undertake preliminary testing of an intervention of nurse-led community care program, the Network Collaborative Action Plan (N-CAP), to assess the impact on disease severity and patient satisfaction. A quasi-experimental study, using historical controls, evaluated a collaborative nurse-led intervention to promote coordination and continuity of care for patients with chronic illness. Participants, diagnosed with chronic obstructive lung disease (COPD), coronary heart disease (CHD) and chronic heart failure (CHF) were recruited. Prospective consecutive patient meeting the study criteria (n=47) were assigned into the control group and following development and implementation of the intervention eligible consenting patients were enrolled in the experimental group (n=44). Participants in the experimental group had significantly tower scores on severity of disease measurements during the third week (F = 4.61, p = 0.035) and the eighth week hospital (F = 4.30, p = .041) following hospital discharge than those in the control group. Participants in the experimental group expressed significantly higher scores on satisfaction with community care than those in the control group. A nurse-led, collaboratively developed program has potential to improve satisfaction and decrease symptom development in people with chronic illnesses in Thailand.

Regulation of cardiac excitation and contraction by p21 activated kinase-1.

PubMed

Ke, Yunbo; Lei, Ming; Solaro, R John

2008-01-01

Cardiac excitation and contraction are regulated by a variety of signaling molecules. Central to the regulatory scheme are protein kinases and phosphatases that carry out reversible phosphorylation of different effectors. The process of beta-adrenergic stimulation mediated by cAMP dependent protein kinase (PKA) forms a well-known pathway considered as the most significant control mechanism in excitation and contraction as well as many other regulatory mechanisms in cardiac function. However, although dephosphorylation pathways are critical to these regulatory processes, signaling to phosphatases is relatively poorly understood. Emerging evidence indicates that regulation of phosphatases, which dampen the effect of beta-adrenergic stimulation, is also important. We review here functional studies of p21 activated kinase-1 (Pak1) and its potential role as an upstream signal for protein phosphatase PP2A in the heart. Pak1 is a serine/threonine protein kinase directly activated by the small GTPases Cdc42 and Rac1. Pak1 is highly expressed in different regions of the heart and modulates the activities of ion channels, sarcomeric proteins, and other phosphoproteins through up-regulation of PP2A activity. Coordination of Pak1 and PP2A activities is not only potentially involved in regulation of normal cardiac function, but is likely to be important in patho-physiological conditions.

Association Study of Gut Flora in Coronary Heart Disease through High-Throughput Sequencing.

PubMed

Cui, Li; Zhao, Tingting; Hu, Haibing; Zhang, Wen; Hua, Xiuguo

2017-01-01

Objectives. We aimed to explore the impact of gut microbiota in coronary heart disease (CHD) patients through high-throughput sequencing. Methods. A total of 29 CHD in-hospital patients and 35 healthy volunteers as controls were included. Nucleic acids were extracted from fecal samples, followed by α diversity and principal coordinate analysis (PCoA). Based on unweighted UniFrac distance matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were created. Results. After data optimization, an average of 121312 ± 19293 reads in CHD patients and 234372 ± 108725 reads in controls was obtained. Reads corresponding to 38 phyla, 90 classes, and 584 genera were detected in CHD patients, whereas 40 phyla, 99 classes, and 775 genera were detected in controls. The proportion of phylum Bacteroidetes (56.12%) was lower and that of phylum Firmicutes was higher (37.06%) in CHD patients than those in the controls (60.92% and 32.06%, P < 0.05). PCoA and UPGMA tree analysis showed that there were significant differences of gut microbial compositions between the two groups. Conclusion. The diversity and compositions of gut flora were different between CHD patients and healthy controls. The incidence of CHD might be associated with the alteration of gut microbiota.

New Mathematical Model for the Surface Area of the Left Ventricle by the Truncated Prolate Spheroid

PubMed Central

Vale, Marcos de Paula; Martinez, Carlos Barreira

2017-01-01

The main aim of this study was the formula application of the superficial area of a truncated prolate spheroid (TPS) in Cartesian coordinates in obtaining a cardiac parameter that is not so much discussed in literature, related to the left ventricle (LV) surface area of the human heart, by age and sex. First we obtain a formula for the area of a TPS. Then a simple mathematical model of association of the axes measures of a TPS with the axes of the LV is built. Finally real values of the average dimensions of the humans LV are used to measure surface areas approximations of this heart chamber. As a result, the average superficial area of LV for normal patients is obtained and it is observed that the percentage differences of areas between men and women and their consecutive age groups are constant. A strong linear correlation between the obtained areas and the ventricular volumes normalized by the body areas was observed. The obtained results indicate that the superficial area of the LV, besides enabling a greater knowledge of the geometrical characteristics of the human LV, may be used as one of the normality cardiac verification criteria and be useful for medical and biological applications. PMID:28547001

Asian tsunami relief: Department of Defense public health response: policy and strategic coordination considerations.

PubMed

Tarantino, Dave

2006-10-01

The Asian tsunami of December 26, 2004, was one of the most devastating natural disasters in modern history. In particular, this disaster created massive, unique, public health threats, necessitating equally massive public health response efforts. The U.S. government (USG), including the Department of Defense (DoD), played a pivotal role in the response. This article examines some of the central policy issues and strategic coordination and planning measures involved in the public health response. The nearly unanimous consensus of international public health experts has been that the potential public health crisis in the aftermath of the Asian tsunami was averted largely because of the coordinated efforts of host nation officials and professionals, international and nongovernmental health organizations, and bilateral donors, especially the USG, including the DoD. The DoD played a central role in public health efforts through coordination and communication assistance, logistical and materiel support, disease surveillance activities, health needs assessments, and the contributions of the USS Mercy hospital ship. The core lessons involve the importance of an early, dedicated, public health response as a component of the overall disaster relief effort, as well as seamless coordination of health sector stakeholders in the USG and with those of the international community and affected host nations, which allows each organization to play to its strengths and to avoid duplication. The Asian tsunami relief effort highlighted the value of civil-military cooperation in disaster relief, particularly in the area of public health. The prominent role of the DoD in tsunami relief efforts, including public health efforts, also yielded beneficial secondary effects by bolstering security cooperation and winning "hearts and minds" in the region.

Care Coordination Challenges Among High-Needs, High-Costs Older Adults in a Medigap Plan.

PubMed

Wells, Timothy S; Bhattarai, Gandhi R; Hawkins, Kevin; Cheng, Yan; Ruiz, Joann; Barnowski, Cynthia A; Spivack, Barney; Yeh, Charlotte S

Many adults 65 years or older have high health care needs and costs. Here, we describe their care coordination challenges. Individuals with an AARP Medicare Supplement Insurance plan insured by UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare Insurance Company of New York). The three groups included the highest needs, highest costs (the "highest group"), the high needs, high costs (the "high group"), and the "all other group." Eligibility was determined by applying an internally developed algorithm based upon a number of criteria, including hierarchical condition category score, the Optum ImpactPro prospective risk score, as well as diagnoses of coronary artery disease, congestive heart failure, or diabetes. The highest group comprised 2%, although consumed 12% of health care expenditures. The high group comprised 20% and consumed 46% of expenditures, whereas the all other group comprised 78% and consumed 42% of expenditures. On average, the highest group had $102,798 in yearly health care expenditures, compared with $34,610 and $7,634 for the high and all other groups, respectively. Fifty-seven percent of the highest group saw 16 or more different providers annually, compared with 21% and 2% of the high and all other groups, respectively. Finally, 28% of the highest group had prescriptions from at least seven different providers, compared with 20% and 5% of the high and all other groups, respectively. Individuals with high health care needs and costs have visits to numerous health care providers and receive multiple prescriptions for pharmacotherapy. As a result, these individuals can become overwhelmed trying to manage and coordinate their health care needs. Care coordination programs may help these individuals coordinate their care.

Pediatric Solid Organ Transplant Recipients: Transition to Home and Chronic Illness Care

PubMed Central

Lerret, Stacee M; Weiss, Marianne; Stendahl, Gail; Chapman, Shelley; Menendez, Jerome; Williams, Laurel; Nadler, Michelle; Neighbors, Katie; Amsden, Katie; Cao, Yumei; Nugent, Melodee; Alonso, Estella; Simpson, Pippa

2014-01-01

Pediatric solid organ transplant recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child’s complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at 3-week, 3-month, and 6-months following discharge from the hospital. Care coordination (p = .02) and quality of discharge teaching (p < .01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = .02) at 3-weeks, adherence with medication administration (p = .03) at 3-months, and post-discharge coping difficulty (p = .04) and family management (p = .02) at 6-months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care. PMID:25425201

Costs of the 'Hartslag Limburg' community heart health intervention

PubMed Central

Ronckers, Emma T; Groot, Wim; Steenbakkers, Mieke; Ruland, Erik; Ament, Andre

2006-01-01

Background Little is known about the costs of community programmes to prevent cardiovascular diseases. The present study calculated the economic costs of all interventions within a Dutch community programme called Hartslag Limburg, in such a way as to facilitate generalisation to other countries. It also calculated the difference between the economic costs and the costs incurred by the coordinating institution. Methods Hartslag Limburg was a large-scale community programme that consisted of many interventions to prevent cardiovascular diseases. The target population consisted of all inhabitants of the region (n = 180.000). Special attention was paid to reach persons with a low socio-economic status. Costs were calculated using the guidelines for economic evaluation in health care. An overview of the material and staffing input involved was drawn up for every single intervention, and volume components were attached to each intervention component. These data were gathered during to the implementation of the intervention. Finally, the input was valued, using Dutch price levels for 2004. Results The economic costs of the interventions that were implemented within the five-year community programme (n = 180,000) were calculated to be about €900,000. €555,000 was spent on interventions to change people's exercise patterns, €250,000 on improving nutrition, €50,000 on smoking cessation, and €45,000 on lifestyle in general. The coordinating agency contributed about 10% to the costs of the interventions. Other institutions that were part of the programme's network and external subsidy providers contributed the other 90% of the costs. Conclusion The current study calculated the costs of a community programme in a detailed and systematic way, allowing the costs to be easily adapted to other countries and regions. The study further showed that the difference between economic costs and the costs incurred by the coordinating agency can be very large. Cost sharing was facilitated by the unique approach used in the Hartslag Limburg programme. PMID:16512909

Coronary veins determine the pattern of sympathetic innervation in the developing heart

PubMed Central

Nam, Joseph; Onitsuka, Izumi; Hatch, John; Uchida, Yutaka; Ray, Saugata; Huang, Siyi; Li, Wenling; Zang, Heesuk; Ruiz-Lozano, Pilar; Mukouyama, Yoh-suke

2013-01-01

Anatomical congruence of peripheral nerves and blood vessels is well recognized in a variety of tissues. Their physical proximity and similar branching patterns suggest that the development of these networks might be a coordinated process. Here we show that large diameter coronary veins serve as an intermediate template for distal sympathetic axon extension in the subepicardial layer of the dorsal ventricular wall of the developing mouse heart. Vascular smooth muscle cells (VSMCs) associate with large diameter veins during angiogenesis. In vivo and in vitro experiments demonstrate that these cells mediate extension of sympathetic axons via nerve growth factor (NGF). This association enables topological targeting of axons to final targets such as large diameter coronary arteries in the deeper myocardial layer. As axons extend along veins, arterial VSMCs begin to secrete NGF, which allows axons to reach target cells. We propose a sequential mechanism in which initial axon extension in the subepicardium is governed by transient NGF expression by VSMCs as they are recruited to coronary veins; subsequently, VSMCs in the myocardium begin to express NGF as they are recruited by remodeling arteries, attracting axons toward their final targets. The proposed mechanism underlies a distinct, stereotypical pattern of autonomic innervation that is adapted to the complex tissue structure and physiology of the heart. PMID:23462468

A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress

PubMed Central

Judge, Luke M.; Perez-Bermejo, Juan A.; Truong, Annie; Ribeiro, Alexandre J.S.; Yoo, Jennie C.; Jensen, Christina L.; Mandegar, Mohammad A.; Huebsch, Nathaniel; Kaake, Robyn M.; So, Po-Lin; Srivastava, Deepak; Krogan, Nevan J.

2017-01-01

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity. PMID:28724793

A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress.

PubMed

Judge, Luke M; Perez-Bermejo, Juan A; Truong, Annie; Ribeiro, Alexandre Js; Yoo, Jennie C; Jensen, Christina L; Mandegar, Mohammad A; Huebsch, Nathaniel; Kaake, Robyn M; So, Po-Lin; Srivastava, Deepak; Pruitt, Beth L; Krogan, Nevan J; Conklin, Bruce R

2017-07-20

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity.

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure.

PubMed

Ziman, Melanie E; Bui, Hien T; Smith, Craig S; Tsukiji, Lori A; Asmatey, Veda M; Chu, Steven B; Miano, John S

2012-04-01

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.

The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.

PubMed

Flotte, Terence R; Daniels, Eric; Benson, Janet; Bevett-Rose, Jeneé M; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie; Sepelak, Susan; van der Loo, Johannes C M; Wilson, James M; McDonald, Cheryl L

2017-12-01

Over a 10-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice clinical-grade vector cores for recombinant adeno-associated virus and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early-phase clinical trials. In addition, the GTRP has utilized a Steering Committee and a Scientific Review Board to guide overall progress and effectiveness and to evaluate individual proposals. These resources have been deployed to assist 82 investigators with 172 approved service proposals. These efforts have assisted in clinical trial implementation across a wide range of genetic, cardiac, pulmonary, and blood diseases. Program outcomes and potential future directions of the program are discussed.

Feeling the right force: How to contextualize the cell mechanical behavior in physiologic turnover and pathologic evolution of the cardiovascular system.

PubMed

Pesce, Maurizio; Santoro, Rosaria

2017-03-01

Although traditionally linked to the physiology of tissues in 'motion', the ability of the cells to transduce external forces into coordinated gene expression programs is emerging as an integral component of the fundamental structural organization of multicellular organisms with consequences for cell differentiation even from the beginning of embryonic development. The ability of the cells to 'feel' the surrounding mechanical environment, even in the absence of tissue motion, is then translated into 'positional' or 'social' sensing that instructs, before the organ renewal, the correct patterning of the embryos. In the present review, we will highlight how these basic concepts, emerging from the employment of novel cell engineering tools, can be linked to pathophysiology of the cardiovascular system, and may contribute to understanding the molecular bases of some of the major cardiovascular diseases like heart failure, heart valve stenosis and failure of the venous aorto-coronary bypass. Copyright © 2016 Elsevier Inc. All rights reserved.

CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

PubMed

Huynh, Kevin W; Jiang, Jiansen; Abuladze, Natalia; Tsirulnikov, Kirill; Kao, Liyo; Shao, Xuesi; Newman, Debra; Azimov, Rustam; Pushkin, Alexander; Zhou, Z Hong; Kurtz, Ira

2018-03-02

Na + -coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na + -coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.

Cardiac and respiratory patterns synchronize between persons during choir singing.

PubMed

Müller, Viktor; Lindenberger, Ulman

2011-01-01

Dyadic and collective activities requiring temporally coordinated action are likely to be associated with cardiac and respiratory patterns that synchronize within and between people. However, the extent and functional significance of cardiac and respiratory between-person couplings have not been investigated thus far. Here, we report interpersonal oscillatory couplings among eleven singers and one conductor engaged in choir singing. We find that: (a) phase synchronization both in respiration and heart rate variability increase significantly during singing relative to a rest condition; (b) phase synchronization is higher when singing in unison than when singing pieces with multiple voice parts; (c) directed coupling measures are consistent with the presence of causal effects of the conductor on the singers at high modulation frequencies; (d) the different voices of the choir are reflected in network analyses of cardiac and respiratory activity based on graph theory. Our results suggest that oscillatory coupling of cardiac and respiratory patterns provide a physiological basis for interpersonal action coordination.

Cardiac and Respiratory Patterns Synchronize between Persons during Choir Singing

PubMed Central

Müller, Viktor; Lindenberger, Ulman

2011-01-01

Dyadic and collective activities requiring temporally coordinated action are likely to be associated with cardiac and respiratory patterns that synchronize within and between people. However, the extent and functional significance of cardiac and respiratory between-person couplings have not been investigated thus far. Here, we report interpersonal oscillatory couplings among eleven singers and one conductor engaged in choir singing. We find that: (a) phase synchronization both in respiration and heart rate variability increase significantly during singing relative to a rest condition; (b) phase synchronization is higher when singing in unison than when singing pieces with multiple voice parts; (c) directed coupling measures are consistent with the presence of causal effects of the conductor on the singers at high modulation frequencies; (d) the different voices of the choir are reflected in network analyses of cardiac and respiratory activity based on graph theory. Our results suggest that oscillatory coupling of cardiac and respiratory patterns provide a physiological basis for interpersonal action coordination. PMID:21957466

Commandeering Channel Voltage Sensors for Secretion, Cell Turgor, and Volume Control.

PubMed

Karnik, Rucha; Waghmare, Sakharam; Zhang, Ben; Larson, Emily; Lefoulon, Cécile; Gonzalez, Wendy; Blatt, Michael R

2017-01-01

Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate turgor, mineral and water transport. Plants use strongly electrogenic H + -ATPases, and the substantial membrane voltages they foster, to drive solute accumulation and generate turgor pressure for cell expansion. Vesicle traffic adds membrane surface and contributes to wall remodelling as the cell grows. Although a balance between vesicle traffic and ion transport is essential for cell turgor and volume control, the mechanisms coordinating these processes have remained obscure. Recent discoveries have now uncovered interactions between conserved subsets of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that drive the final steps in secretory vesicle traffic and ion channels that mediate in inorganic solute uptake. These findings establish the core of molecular links, previously unanticipated, that coordinate cellular homeostasis and cell expansion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Image Pro Plus Software to Develop Particle Mapping on Genesis Solar Wind Collector Surfaces

NASA Technical Reports Server (NTRS)

Rodriquez, Melissa C.; Allton, J. H.; Burkett, P. J.

2012-01-01

The continued success of the Genesis mission science team in analyzing solar wind collector array samples is partially based on close collaboration of the JSC curation team with science team members who develop cleaning techniques and those who assess elemental cleanliness at the levels of detection. The goal of this collaboration is to develop a reservoir of solar wind collectors of known cleanliness to be available to investigators. The heart and driving force behind this effort is Genesis mission PI Don Burnett. While JSC contributes characterization, safe clean storage, and benign collector cleaning with ultrapure water (UPW) and UV ozone, Burnett has coordinated more exotic and rigorous cleaning which is contributed by science team members. He also coordinates cleanliness assessment requiring expertise and instruments not available in curation, such as XPS, TRXRF [1,2] and synchrotron TRXRF. JSC participates by optically documenting the particle distributions as cleaning steps progress. Thus, optical document supplements SEM imaging and analysis, and elemental assessment by TRXRF.

Expression and Production of SH2 Domain Proteins.

PubMed

Liu, Bernard A; Ogiue-Ikeda, Mari; Machida, Kazuya

2017-01-01

The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.

Patient-Centered Medical Home Features and Health Care Expenditures of Medicare Beneficiaries with Chronic Disease Dyads.

PubMed

Philpot, Lindsey M; Stockbridge, Erica L; Padrón, Norma A; Pagán, José A

2016-06-01

Three out of 4 Medicare beneficiaries have multiple chronic conditions, and managing the care of this growing population can be complex and costly because of care coordination challenges. This study assesses how different elements of the patient-centered medical home (PCMH) model may impact the health care expenditures of Medicare beneficiaries with the most prevalent chronic disease dyads (ie, co-occurring high cholesterol and high blood pressure, high cholesterol and heart disease, high cholesterol and diabetes, high cholesterol and arthritis, heart disease and high blood pressure). Data from the 2007-2011 Medical Expenditure Panel Survey suggest that increased access to PCMH features may differentially impact the distribution of health care expenditures across health care service categories depending on the combination of chronic conditions experienced by each beneficiary. For example, having no difficulty contacting a provider after regular hours was associated with significantly lower outpatient expenditures for beneficiaries with high cholesterol and diabetes (n = 635; P = 0.038), but it was associated with significantly higher inpatient expenditures for beneficiaries with high blood pressure and high cholesterol (n = 1599; P = 0.015), and no significant differences in expenditures in any category for beneficiaries with high blood pressure and heart disease (n = 1018; P > 0.05 for all categories). However, average total health care expenditures are largely unaffected by implementing the PCMH features considered. Understanding how the needs of Medicare beneficiaries with multiple chronic conditions can be met through the adoption of the PCMH model is important not only to be able to provide high-quality care but also to control costs. (Population Health Management 2016;19:206-211).

[Effects of multidisciplinary blood management strategy on transfusion and outcomes in patients undergoing valvular heart surgery].

PubMed

Ji, Hongwen; Li, Zhiyuan; Sun, Hansong; Li, Lihuan; Long, Cun; Ma, Li; Chen, Lei; Wang, Wei; Hu, Shengshou

2014-02-25

To evaluate the effect of multidisciplinary blood management strategy in adults patients undergoing valvular heart surgery. A multidisciplinary patient blood management (PBM) strategy was instituted in Fuwai Hospital since January 2009. It includes Establishment of a multidisciplinary blood transfusion management team and designation of a coordinator; Enactment perioperative transfusion triggers (Hb < 80 g/L) for adults patients undergoing cardiac surgery; recommendation of antifibrinolytics, cell salvage, reduced cardiopulmonary bypass circuit; setting up Blood Consumption Announcement and Scoring System, which regularly publishes notifications of blood volume consumed per case, per single procedure and per surgeon. Clinical date before and after multidisciplinary patient blood management strategy will be presented. A total of 3 951 consecutive patients underwent Valvular Heart Surgery were analyzed. 1 713 cases were in pre-PBM group, and 2 238 cases were in post-PBM group. Both incidence and average units of allogeneic red blood cell transfusion perioperatively in post-PBM group were decreased (28.5% vs 75.3%, P = 0.000, and 1.2 U vs 4.0 U, P = 0.000). The postoperative length of stay in hospital and incidence of pneumonia were reduced in post-PBM group (8.2 d vs 10.5 d, P = 0.02, and 2.7% vs 3.5%, P = 0.04). The post-PBM group had lower in-hospital mortality (0.6% vs 1.2%, P = 0.000). Multidisciplinary patient blood management strategy significantly reduced blood transfusion, morbidity and mortality in patients underwent valvular heart surgery. It save plenty of blood resources.

Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments

PubMed Central

Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm

2016-01-01

Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease. PMID:27162358

Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments.

PubMed

Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm

2016-05-24

Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease.

e_Disease Management. A system for the management of the chronic conditions.

PubMed

Guillén, Sergio; Meneu, Maria Teresa; Serafin, Riccardo; Arredondo, Maria Teresa; Castellano, Elena; Valdivieso, Bernardo

2010-01-01

Disease Management (DM) is a system of coordinated healthcare intervention and communications for populations with conditions in which patient self-care efforts are significant. e-DM makes reference to processes of DM based on clinical guidelines sustained in the scientific medical evidence and supported by the intervention of Information and Telecommunication Technology (ICT) in all levels where these plans are developed. This paper discusses the design and implementation of a e-DM system which meets the requirements for the integrated chronic disease management following the recommendations of the Disease Management Association and the American Heart Association.

Cardiac integrins the ties that bind.

PubMed

Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

1998-01-01

An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

Beyond Synchrony: Joint Action in a Complex Production Task Reveals Beneficial Effects of Decreased Interpersonal Synchrony

PubMed Central

Mitkidis, Panagiotis; Roepstorff, Andreas

2016-01-01

A variety of joint action studies show that people tend to fall into synchronous behavior with others participating in the same task, and that such synchronization is beneficial, leading to greater rapport, satisfaction, and performance. It has been noted that many of these task environments require simple interactions that involve little planning of action coordination toward a shared goal. The present study utilized a complex joint construction task in which dyads were instructed to build model cars while their hand movements and heart rates were measured. Participants built these models under varying conditions, delimiting how freely they could divide labor during a build session. While hand movement synchrony was sensitive to the different tasks and outcomes, the heart rate measure did not show any effects of interpersonal synchrony. Results for hand movements show that the more participants were constrained by a particular building strategy, the greater their behavioral synchrony. Within the different conditions, the degree of synchrony was predictive of subjective satisfaction and objective product outcomes. However, in contrast to many previous findings, synchrony was negatively associated with superior products, and, depending on the constraints on the interaction, positively or negatively correlated with higher subjective satisfaction. These results show that the task context critically shapes the role of synchronization during joint action, and that in more complex tasks, not synchronization of behavior, but rather complementary types of behavior may be associated with superior task outcomes. PMID:27997558

Mathematical Development and Computational Analysis of Harmonic Phase-Magnetic Resonance Imaging (HARP-MRI) Based on Bloch Nuclear Magnetic Resonance (NMR) Diffusion Model for Myocardial Motion.

PubMed

Dada, Michael O; Jayeoba, Babatunde; Awojoyogbe, Bamidele O; Uno, Uno E; Awe, Oluseyi E

2017-09-13

Harmonic Phase-Magnetic Resonance Imaging (HARP-MRI) is a tagged image analysis method that can measure myocardial motion and strain in near real-time and is considered a potential candidate to make magnetic resonance tagging clinically viable. However, analytical expressions of radially tagged transverse magnetization in polar coordinates (which is required to appropriately describe the shape of the heart) have not been explored because the physics required to directly connect myocardial deformation of tagged Nuclear Magnetic Resonance (NMR) transverse magnetization in polar geometry and the appropriate harmonic phase parameters are not yet available. The analytical solution of Bloch NMR diffusion equation in spherical geometry with appropriate spherical wave tagging function is important for proper analysis and monitoring of heart systolic and diastolic deformation with relevant boundary conditions. In this study, we applied Harmonic Phase MRI method to compute the difference between tagged and untagged NMR transverse magnetization based on the Bloch NMR diffusion equation and obtained radial wave tagging function for analysis of myocardial motion. The analytical solution of the Bloch NMR equations and the computational simulation of myocardial motion as developed in this study are intended to significantly improve healthcare for accurate diagnosis, prognosis and treatment of cardiovascular related deceases at the lowest cost because MRI scan is still one of the most expensive anywhere. The analysis is fundamental and significant because all Magnetic Resonance Imaging techniques are based on the Bloch NMR flow equations.

Cardiac rehabilitation with a nurse case manager (GoHeart) across local and regional health authorities improves risk factors, self-care and psychosocial outcomes. A one-year follow-up study.

PubMed

Hansen, Vibeke Brogaard; Maindal, Helle Terkildsen

2014-01-01

In Denmark, the local and regional health authorities share responsibility for cardiac rehabilitation (CR). The objective was to assess effectiveness of CR across sectors coordinated by a nurse case manager (NCM). A one-year follow-up study. A CR programme (GoHeart) was evaluated in a cohort at Lillebaelt Hospital Vejle, DK from 2010 to 2011. Consecutive patients admitted to CR were included. The inclusion criteria were the event of acute myocardial infarction or stable angina and invasive revascularization (left ventricular ejection fraction (LVEF) ≥45%). Cardiac risk factors, stratified self-care and self-reported psychosocial factors (SF12 and Hospital Anxiety and Depression Scale (HADS)) were assessed at admission (phase IIa), at three months at discharge (phase IIb) and at one-year follow-up (phase III). Intention-to-treat and predefined subgroup analysis on sex was performed. Of 241 patients, 183 (75.9%) were included (mean age 63.8 years). At discharge improvements were found in total-cholesterol (p < 0.001), low density lipoprotein (LDL; p < 0.001), functional capacities (metabolic equivalent of tasks (METS), p < 0.01), self-care management (p < 0.001), Health status Short Form 12 version (SF12; physical; p < 0.001 and mental; p < 0.01) and in depression symptoms (p < 0.01). At one-year follow-up these outcomes were maintained; additionally there was improvement in body mass index (BMI; p < 0.05), and high density lipoprotein (HDL; p < 0.05). There were no sex differences. CR shared between local and regional health authorities led by a NCM (GoHeart) improves risk factors, self-care and psychosocial factors. Further improvements in most variables were at one-year follow-up.

Acute coordinative exercise improves attentional performance in adolescents.

PubMed

Budde, Henning; Voelcker-Rehage, Claudia; Pietrabyk-Kendziorra, Sascha; Ribeiro, Pedro; Tidow, Günter

2008-08-22

Teachers complain about growing concentration deficits and reduced attention in adolescents. Exercise has been shown to positively affect cognitive performance. Due to the neuronal connection between the cerebellum and the frontal cortex, we hypothesized that cognitive performance might be influenced by bilateral coordinative exercise (CE) and that its effect on cognition might be already visible after short bouts of exercise. One hundred and fifteen healthy adolescents aged 13-16 years of an elite performance school were randomly assigned to an experimental and a control group and tested using the d2-test, a test of attention and concentration. Both groups performed the d2-test after a regular school lesson (pre-test), after 10 min of coordinative exercise and of a normal sport lesson (NSL, control group), respectively (post-test). Exercise was controlled for heart rate (HR). CE and NSL enhanced the d2-test performance from pre- to post-test significantly. ANOVA revealed a significant group (CE, NSL) by performance interaction in the d2-test indicating a higher improvement of CE as compared to NSL. HR was not significantly different between the groups. CE was more effective in completing the concentration and attention task. With the HR being the same in both groups we assume that the coordinative character of the exercise might be responsible for the significant differences. CE might lead to a pre-activation of parts of the brain which are also responsible for mediating functions like attention. Thus, our results support the request for more acute CE in schools, even in elite performance schools.

Promise-based management: the essence of execution.

PubMed

Sull, Donald N; Spinosa, Charles

2007-04-01

Critical initiatives stall for a variety of reasons--employee disengagement, a lack of coordination between functions, complex organizational structures that obscure accountability, and so on. To overcome such obstacles, managers must fundamentally rethink how work gets done. Most of the challenges stem from broken or poorly crafted commitments. That's because every company is, at its heart, a dynamic network of promises made between employees and colleagues, customers, outsourcing partners, or other stakeholders. Executives can overcome many problems in the short-term and foster productive, reliable workforces for the long-term by practicing what the authors call "promise-based management," which involves cultivating and coordinating commitments in a systematic way. Good promises share five qualities: They are public, active, voluntary, explicit, and mission based. To develop and execute an effective promise, the "provider" and the "customer" in the deal should go through three phases of conversation. The first, achieving a meeting of minds, entails exploring the fundamental questions of coordinated effort: What do you mean? Do you understand what I mean? What should I do? What will you do? Who else should we talk to? In the next phase, making it happen, the provider executes on the promise. In the final phase, closing the loop, the customer publicly declares that the provider has either delivered the goods or failed to do so. Leaders must weave and manage their webs of promises with great care-encouraging iterative conversation and making sure commitments are fulfilled reliably. If they do, they can enhance coordination and cooperation among colleagues, build the organizational agility required to seize new business opportunities, and tap employees' entrepreneurial energies.

Perceived Impact of Care Managers’ Work on Patient and Clinician Outcomes

PubMed Central

Carayon, Pascale; Hundt, Ann Schoofs; Hoonakker, Peter; Kianfar, Sarah; Alyousef, Bashar; Salek, Doreen; Cartmill, Randi; Walker, James M.; Tomcavage, Janet

2015-01-01

Objectives The aim of this study is to assess the contributions of care management as perceived by care managers themselves. Study Design Focus groups and interviews with care managers who coordinate care for chronic obstructive pulmonary disease and congestive heart failure patients, as well as patients undergoing major surgery. Methods We collected data in focus groups and interviews with 12 care managers working in the Keystone Beacon Community project, including 5 care managers working in hospitals, 2 employed in outpatient clinics and 4 telephoning discharged patients from a Transitions of Care (TOC) call center. Results Inpatient care managers believe that (1) ensuring primary care provider follow-up, (2) coordinating appropriate services, (3) providing patient education, and (4) ensuring accurate medication reconciliation have the greatest impact on patient clinical outcomes. In contrast, outpatient and TOC care managers believe that (1) teaching patients the signs and symptoms of acute exacerbations and (2) building effective relationships with patients improve patient outcomes most. Some care management activities were perceived to have greater impact on patients with certain conditions (e.g., outpatient and TOC care managers saw effective relationships as having more impact on patients with COPD). All care managers believed that relationships with patients have the greatest impact on patient satisfaction, while the support they provide clinicians has the greatest impact on clinician satisfaction. Conclusions These findings may improve best practice for care managers by focusing interventions on the most effective activities for patients with specific medical conditions. PMID:26273476

Influence of the heart rate and atrioventricular delays on vortex evolution and blood transport inside the left ventricle

NASA Astrophysics Data System (ADS)

Hendabadi, Sahar; Martinez-Legazpi, Pablo; Benito, Yolanda; Bermejo, Javier; Del Alamo, Juan Carlos; Shadden, Shawn

2013-11-01

Cardiac resynchronization therapy (CRT) is used to help restore coordinated pumping of the ventricles by overcoming delays in electrical conduction due to cardiac disease. This is accomplished by a specialized cardiac pacemaker that is able to adjust the atrioventricular (AV) delay.A major clinical challenge is to adjust the pacing strategy to best coordinate the blood flow mechanics of ventricular filling and ejection. To this end, we have studied the difference in the vortex formation and its evolution inside the left ventricle (LV) for 4 different AV delays in a cohort of patients with implanted pacemakers. A reconstruction algorithm was used to obtain 2D velocity over the apical long-axis view of the LV from color Doppler and B-mode ultrasound data. To study blood transport, we have identified Lagrangian coherent structures to determine moving boundaries of the blood volumes injected to the LV in diastole and ejected to the aorta in systole. In all cases, we have analyzed the differences in filling and ejection patterns and the blood transport during the E-wave and A-wave formation.Finally we have assessed the influence of the AV delay on 2 indices of stasis, direct flow and residence time.The findings shed insight to the optimization of AV delays in patients undergoing CRT. NIH award 5R21HL108268 and grants PIS09/02603 and RD06/0010 from the Plan Nacional de Investigacion Cientifica, Spain.

Health system responsiveness and chronic disease care - What is the role of disease management programs? An analysis based on cross-sectional survey and administrative claims data.

PubMed

Röttger, Julia; Blümel, Miriam; Linder, Roland; Busse, Reinhard

2017-07-01

Health system responsiveness is an important aspect of health systems performance. The concept of responsiveness relates to the interpersonal and contextual aspects of health care. While disease management programs (DMPs) aim to improve the quality of health care (e.g. by improving the coordination of care), it has not been analyzed yet whether these programs improve the perceived health system responsiveness. Our study aims to close this gap by analyzing the differences in the perceived health system responsiveness between DMP-participants and non-participants. We used linked survey- and administrative claims data from 7037 patients with coronary heart disease in Germany. Of those, 5082 were enrolled and 1955 were not enrolled in the DMP. Responsiveness was assessed with an adapted version of the WHO responsiveness questionnaire in a postal survey in 2013. The survey covered 9 dimensions of responsiveness and included 17 items for each, GP and specialist care. Each item had five answer categories (very good - very bad). We handled missing values in the covariates by multiple imputation and applied propensity score matching (PSM) to control for differences between the two groups (DMP/non-DMP). We used Wilcoxon-signed-rank and McNemar test to analyze differences regarding the reported responsiveness. The PSM led to a matched and well balanced sample of 1921 pairs. Overall, DMP-participants rated the responsiveness of care more positive. The main difference was found for the coordination of care at the GP, with 62.0% of 1703 non-participants reporting a "good" or "very good" experience, compared to 69.1% of 1703 participants (p < 0.001). The results of our study indicate an overall high responsiveness for CHD-care, as well for DMP-participants as for non-participants. Yet, the results also clearly indicate that there is still a need to improve the coordination of care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Meshless deformable models for 3D cardiac motion and strain analysis from tagged MRI.

PubMed

Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Schaerer, Joël; Qian, Zhen; Huh, Suejung; Metaxas, Dimitris; Axel, Leon

2015-01-01

Tagged magnetic resonance imaging (TMRI) provides a direct and noninvasive way to visualize the in-wall deformation of the myocardium. Due to the through-plane motion, the tracking of 3D trajectories of the material points and the computation of 3D strain field call for the necessity of building 3D cardiac deformable models. The intersections of three stacks of orthogonal tagging planes are material points in the myocardium. With these intersections as control points, 3D motion can be reconstructed with a novel meshless deformable model (MDM). Volumetric MDMs describe an object as point cloud inside the object boundary and the coordinate of each point can be written in parametric functions. A generic heart mesh is registered on the TMRI with polar decomposition. A 3D MDM is generated and deformed with MR image tagging lines. Volumetric MDMs are deformed by calculating the dynamics function and minimizing the local Laplacian coordinates. The similarity transformation of each point is computed by assuming its neighboring points are making the same transformation. The deformation is computed iteratively until the control points match the target positions in the consecutive image frame. The 3D strain field is computed from the 3D displacement field with moving least squares. We demonstrate that MDMs outperformed the finite element method and the spline method with a numerical phantom. Meshless deformable models can track the trajectory of any material point in the myocardium and compute the 3D strain field of any particular area. The experimental results on in vivo healthy and patient heart MRI show that the MDM can fully recover the myocardium motion in three dimensions. Copyright © 2014. Published by Elsevier Inc.

Meshless deformable models for 3D cardiac motion and strain analysis from tagged MRI

PubMed Central

Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Schaerer, Joël; Qian, Zhen; Huh, Suejung; Metaxas, Dimitris; Axel, Leon

2016-01-01

Tagged magnetic resonance imaging (TMRI) provides a direct and noninvasive way to visualize the in-wall deformation of the myocardium. Due to the through-plane motion, the tracking of 3D trajectories of the material points and the computation of 3D strain field call for the necessity of building 3D cardiac deformable models. The intersections of three stacks of orthogonal tagging planes are material points in the myocardium. With these intersections as control points, 3D motion can be reconstructed with a novel meshless deformable model (MDM). Volumetric MDMs describe an object as point cloud inside the object boundary and the coordinate of each point can be written in parametric functions. A generic heart mesh is registered on the TMRI with polar decomposition. A 3D MDM is generated and deformed with MR image tagging lines. Volumetric MDMs are deformed by calculating the dynamics function and minimizing the local Laplacian coordinates. The similarity transformation of each point is computed by assuming its neighboring points are making the same transformation. The deformation is computed iteratively until the control points match the target positions in the consecutive image frame. The 3D strain field is computed from the 3D displacement field with moving least squares. We demonstrate that MDMs outperformed the finite element method and the spline method with a numerical phantom. Meshless deformable models can track the trajectory of any material point in the myocardium and compute the 3D strain field of any particular area. The experimental results on in vivo healthy and patient heart MRI show that the MDM can fully recover the myocardium motion in three dimensions. PMID:25157446

KLF2 and KLF4 control endothelial identity and vascular integrity

PubMed Central

Sangwung, Panjamaporn; Zhou, Guangjin; Nayak, Lalitha; Chan, E. Ricky; Kang, Dong-Won; Zhang, Rongli; Lu, Yuan; Sugi, Keiki; Fujioka, Hisashi; Shi, Hong; Lapping, Stephanie D.; Ghosh, Chandra C.; Higgins, Sarah J.; Parikh, Samir M.; Jain, Mukesh K.

2017-01-01

Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. PMID:28239661

Altered cardiorespiratory coupling in young male adults with excessive online gaming.

PubMed

Chang, Jae Seung; Kim, Eun Young; Jung, Dooyoung; Jeong, Seong Hoon; Kim, Yeni; Roh, Myoung-Sun; Ahn, Yong Min; Hahm, Bong-Jin

2015-09-01

This study aimed to investigate changes in heart rate variability and cardiorespiratory coupling in male college students with problematic Internet use (PIU) excessive gaming type during action video game play to assess the relationship between PIU tendency and central autonomic regulation. Electrocardiograms and respiration were simultaneously recorded from 22 male participants with excessive online gaming and 22 controls during action video game play. Sample entropy (SampEn) was computed to assess autonomic regularity, and cross-SampEn was calculated to quantify autonomic coordination. During video game play, reduced cardiorespiratory coupling (CRC) was observed in individuals with PIU excessive gaming type compared with controls, implicating central autonomic dysregulation. The PIU tendency was associated with the severity of autonomic dysregulation. These findings indicate impaired CRC in PIU excessive gaming type, which may reflect alterations of central inhibitory control over autonomic responses to pleasurable online stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

The Whole Heliosphere Interval: Campaign Summaries and Early Results

NASA Technical Reports Server (NTRS)

Thompson, Barbara J.; Gibson, Sarah E.; Kozyra, Janet U.

2008-01-01

The Whole Heliosphere Interval (WHI) is an internationally coordinated observing and modeling effort to characterize the 3-dimensional interconnected solar-heliospheric-planetary system - a.k.a. the "heliophysical" system. The heart of the WHI campaign is the study of the interconnected 3-D heliophysical domain, from the interior of the Sun, to the Earth, outer planets, and into interstellar space. WHI observing campaigns began with the 3-0 solar structure from solar Carrington Rotation 2068, which ran from March 20 - April 16, 2008. Observations and models of the outer heliosphere and planetary impacts extended beyond those dates as necessary; for example, the solar wind transit time to outer planets can take months. WHI occurs during solar minimum, which optimizes our ability to characterize the 3-D heliosphere and trace the structure to the outer limits of the heliosphere. A summary of some of the key results from the WHI first workshop in August 2008 will be given.

Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology.

PubMed

Stramba-Badiale, Marco; Fox, Kim M; Priori, Silvia G; Collins, Peter; Daly, Caroline; Graham, Ian; Jonsson, Benct; Schenck-Gustafsson, Karin; Tendera, Michal

2006-04-01

Cardiovascular diseases (CVD) are the leading cause of mortality both in men and women. In Europe, about 55% of all females' deaths are caused by CVD, especially coronary heart disease and stroke. Unfortunately, however, the risk of heart disease in women is underestimated because of the perception that women are 'protected' against ischaemic heart disease. What is not fully understood is that women during the fertile age have a lower risk of cardiac events, but this protection fades after menopause thus leaving women with untreated risk factors vulnerable to develop myocardial infarction, heart failure, and sudden cardiac death. Furthermore, clinical manifestations of ischaemic heart disease in women may be different from those commonly observed in males and this factor may account for under-recognition of the disease. The European Society of Cardiology has recently initiated an extensive 'Women at heart' program to coordinate research and educational initiatives on CVD in women. A Policy Conference on CVD in Women was one of the first steps in the development of this program. The objective of the conference was to collect the opinion of experts in the field coming from the European Society of Cardiology member countries to: (1) summarize the state-of-the-art from an European perspective; (2) to identify the scientific gaps on CVD in women; and (3) to delineate the strategies for changing the misperception of CVD in women, improving risk stratification, diagnosis, and therapy from a gender perspective and increasing women representation in clinical trials. The Policy Conference has provided the opportunity to review and comment on the current status of knowledge on CVD in women and to prioritize the actions needed to advance this area of knowledge in cardiology. In the preparation of this document we intend to provide the medical community and the stakeholders of this field with an overview of the more critical aspects that have emerged during the discussion. We also propose some immediate actions that should be undertaken with the hope that synergic activities will be implemented at European level with the support of national health care authorities.

Consensus statement: Palliative and supportive care in advanced heart failure.

PubMed

Goodlin, Sarah J; Hauptman, Paul J; Arnold, Robert; Grady, Kathleen; Hershberger, Ray E; Kutner, Jean; Masoudi, Frederick; Spertus, John; Dracup, Kathleen; Cleary, James F; Medak, Ruth; Crispell, Kathy; Piña, Ileana; Stuart, Brad; Whitney, Christy; Rector, Thomas; Teno, Joan; Renlund, Dale G

2004-06-01

A consensus conference was convened to define the current state and important gaps in knowledge and needed research on "Palliative and Supportive Care in Advanced Heart Failure." Evidence was drawn from expert opinion and from extensive review of the medical literature, evidence-based guidelines, and reviews. The conference identified gaps in current knowledge, practice, and research relating to prognostication, symptom management, and supportive care for advanced heart failure (HF). Specific conclusions include: (1) although supportive care should be integrated throughout treatment of patients with advanced HF, data are needed to understand how to best decrease physical and psychosocial burdens of advanced HF and to meet patient and family needs; (2) prognostication in advanced HF is difficult and data are needed to understand which patients will benefit from which interventions and how best to counsel patients with advanced HF; (3) research is needed to identify which interventions improve quality of life and best achieve the outcomes desired by patients and family members; (4) care should be coordinated between sites of care, and barriers to evidence-based practice must be addressed programmatically; and (5) more research is needed to identify the content and technique of communicating prognosis and treatment options with patients with advanced HF; physicians caring for patients with advanced HF must develop skills to better integrate the patient's preferences into the goals of care.

The Miracle Baby Grows Up: Hypoplastic Left Heart Syndrome in the Adult.

PubMed

Lewis, Matthew; Rosenbaum, Marlon

2017-08-01

Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of the mitral valve, left ventricle, and aorta and is ultimately palliated with a single-ventricle repair. Universally fatal in infancy prior to the advent of modern surgical techniques, the majority of HLHS patients will now reach adulthood. However, despite improvements in early survival, the HLHS population continues to face significant morbidity and early mortality. This review delineates common sources of patient morbidity and highlights areas in need of additional research for this growing segment of the adult congenital heart disease population. It has become increasingly clear that palliated adult single ventricle patients, like those with HLHS, face significant life-long morbidity from elevated systemic venous pressures as a consequence of the Fontan procedure. Downstream organ dysfunction secondary to elevated Fontan pressures has the potential to significantly impact long-term management decisions, including strategies of organ allocation. Because of the presence of a morphologic systemic right ventricle, HLHS patients may be at even higher risk than other adult patients with a Fontan. Because the adult HLHS population continues to grow, recognition of common sources of patient morbidity and mortality is becoming increasingly important. A coordinated effort between patients and providers is necessary to address the many remaining areas of clinical uncertainty to help ensure continued improvement in patient prognosis and quality of life.

Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

PubMed Central

Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

2013-01-01

Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Inferring dynamic gene regulatory networks in cardiac differentiation through the integration of multi-dimensional data.

PubMed

Gong, Wuming; Koyano-Nakagawa, Naoko; Li, Tongbin; Garry, Daniel J

2015-03-07

Decoding the temporal control of gene expression patterns is key to the understanding of the complex mechanisms that govern developmental decisions during heart development. High-throughput methods have been employed to systematically study the dynamic and coordinated nature of cardiac differentiation at the global level with multiple dimensions. Therefore, there is a pressing need to develop a systems approach to integrate these data from individual studies and infer the dynamic regulatory networks in an unbiased fashion. We developed a two-step strategy to integrate data from (1) temporal RNA-seq, (2) temporal histone modification ChIP-seq, (3) transcription factor (TF) ChIP-seq and (4) gene perturbation experiments to reconstruct the dynamic network during heart development. First, we trained a logistic regression model to predict the probability (LR score) of any base being bound by 543 TFs with known positional weight matrices. Second, four dimensions of data were combined using a time-varying dynamic Bayesian network model to infer the dynamic networks at four developmental stages in the mouse [mouse embryonic stem cells (ESCs), mesoderm (MES), cardiac progenitors (CP) and cardiomyocytes (CM)]. Our method not only infers the time-varying networks between different stages of heart development, but it also identifies the TF binding sites associated with promoter or enhancers of downstream genes. The LR scores of experimentally verified ESCs and heart enhancers were significantly higher than random regions (p <10(-100)), suggesting that a high LR score is a reliable indicator for functional TF binding sites. Our network inference model identified a region with an elevated LR score approximately -9400 bp upstream of the transcriptional start site of Nkx2-5, which overlapped with a previously reported enhancer region (-9435 to -8922 bp). TFs such as Tead1, Gata4, Msx2, and Tgif1 were predicted to bind to this region and participate in the regulation of Nkx2-5 gene expression. Our model also predicted the key regulatory networks for the ESC-MES, MES-CP and CP-CM transitions. We report a novel method to systematically integrate multi-dimensional -omics data and reconstruct the gene regulatory networks. This method will allow one to rapidly determine the cis-modules that regulate key genes during cardiac differentiation.

Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH.

PubMed

Meijers, Wouter C; de Boer, Rudolf A; van Veldhuisen, Dirk J; Jaarsma, Tiny; Hillege, Hans L; Maisel, Alan S; Di Somma, Salvatore; Voors, Adriaan A; Peacock, W Frank

2015-12-01

Traditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. This analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180 days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (± SD) age was 71 (± 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180 days (OR 8.1, 95% confidence interval 1.06-50.0, P = 0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P = 0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiolog.

The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS-III): A research program striving to improve blood donor and transfusion recipient outcomes

PubMed Central

Kleinman, Steven; Busch, Michael P; Murphy, Edward L; Shan, Hua; Ness, Paul; Glynn, Simone A.

2014-01-01

Background The Recipient Epidemiology and Donor Evaluation Study -III (REDS-III) is a 7-year multicenter transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute. Study design The domestic component involves 4 blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa which involve US and in-country investigators. Results REDS-III is using two major methods to address key research priorities in blood banking/transfusion medicine. First, there will be numerous analyses of large “core” databases; the international programs have each constructed a donor/donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Secondly, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that are either in progress or scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization; transfusion outcomes; non-infectious transfusion risks; HIV-related safety issues (particularly in the international programs); emerging infectious agents; blood component quality; donor health and safety; and other donor issues. Conclusions It is intended that REDS-III serve as an impetus for more widespread recipient and linked donor-recipient research in the US as well as to help assure a safe and available blood supply in the US and in international locations. PMID:24188564

Immune Modulation of Cardiac Repair and Regeneration: The Art of Mending Broken Hearts

PubMed Central

Zlatanova, Ivana; Pinto, Cristina; Silvestre, Jean-Sébastien

2016-01-01

The accumulation of immune cells is among the earliest responses that manifest in the cardiac tissue after injury. Both innate and adaptive immunity coordinate distinct and mutually non-exclusive events governing cardiac repair, including elimination of the cellular debris, compensatory growth of the remaining cardiac tissue, activation of resident or circulating precursor cells, quantitative and qualitative modifications of the vascular network, and formation of a fibrotic scar. The present review summarizes the mounting evidence suggesting that the inflammatory response also guides the regenerative process following cardiac damage. In particular, recent literature has reinforced the central role of monocytes/macrophages in poising the refreshment of cardiomyocytes in myocardial infarction- or apical resection-induced cardiac insult. Macrophages dictate cardiac myocyte renewal through stimulation of preexisting cardiomyocyte proliferation and/or neovascularization. Nevertheless, substantial efforts are required to identify the nature of these macrophage-derived factors as well as the molecular mechanisms engendered by the distinct subsets of macrophages pertaining in the cardiac tissue. Among the growing inflammatory intermediaries that have been recognized as essential player in heart regeneration, we will focus on the role of interleukin (IL)-6 and IL-13. Finally, it is likely that within the mayhem of the injured cardiac tissue, additional types of inflammatory cells, such as neutrophils, will enter the dance to ignite and refresh the broken heart. However, the protective and detrimental inflammatory pathways have been mainly deciphered in animal models. Future research should be focused on understanding the cellular effectors and molecular signals regulating inflammation in human heart to pave the way for the development of factual therapies targeting the inflammatory compartment in cardiac diseases. PMID:27790620

Immune Modulation of Cardiac Repair and Regeneration: The Art of Mending Broken Hearts.

PubMed

Zlatanova, Ivana; Pinto, Cristina; Silvestre, Jean-Sébastien

2016-01-01

The accumulation of immune cells is among the earliest responses that manifest in the cardiac tissue after injury. Both innate and adaptive immunity coordinate distinct and mutually non-exclusive events governing cardiac repair, including elimination of the cellular debris, compensatory growth of the remaining cardiac tissue, activation of resident or circulating precursor cells, quantitative and qualitative modifications of the vascular network, and formation of a fibrotic scar. The present review summarizes the mounting evidence suggesting that the inflammatory response also guides the regenerative process following cardiac damage. In particular, recent literature has reinforced the central role of monocytes/macrophages in poising the refreshment of cardiomyocytes in myocardial infarction- or apical resection-induced cardiac insult. Macrophages dictate cardiac myocyte renewal through stimulation of preexisting cardiomyocyte proliferation and/or neovascularization. Nevertheless, substantial efforts are required to identify the nature of these macrophage-derived factors as well as the molecular mechanisms engendered by the distinct subsets of macrophages pertaining in the cardiac tissue. Among the growing inflammatory intermediaries that have been recognized as essential player in heart regeneration, we will focus on the role of interleukin (IL)-6 and IL-13. Finally, it is likely that within the mayhem of the injured cardiac tissue, additional types of inflammatory cells, such as neutrophils, will enter the dance to ignite and refresh the broken heart. However, the protective and detrimental inflammatory pathways have been mainly deciphered in animal models. Future research should be focused on understanding the cellular effectors and molecular signals regulating inflammation in human heart to pave the way for the development of factual therapies targeting the inflammatory compartment in cardiac diseases.

[Intrathoracic movement of the normal and hypertrophied hearts measured by biplane coronary cineangiography].

PubMed

Osato, S; Ishikawa, K; Kanamasa, K; Ogai, T; Oda, A; Katori, R

1984-06-01

The shift of the heart during systole within the thorax was measured using bifurcations of the left coronary artery as cineangiographic markers. Biplane coronary cineangiography was performed in 13 normal subjects and 6 patients with non-obstructive hypertrophic cardiomyopathy (HCM). The spatial coordinates (X, Y, Z) of the bifurcations on the cineangiograms were measured using a motion analizer-digitizer-computer system. The systolic excursion of the motion of a bifurcation located at the anterior-basal point of the heart was 1.4 +/- 0.1 (+/-SD) cm leftward, 3.0 +/- 0.3 cm caudally and 2.5 +/- 0.1 cm anteriorly in normal subjects. In the cases with HCM, on the other hand, the bifurcation moved 2.2 +/- 1.1, 2.7 +/- 1.2 and 2.2 +/- 0.6 cm during systole, respectively. The movement at the apex in the normal subjects was 1.7 +/- 0.2 cm rightward, 1.5 +/- 0.2 cm caudally and 1.5 +/- 0.2 cm posteriorly, although the direction was reversed as compared to that of the anterior wall of the cardiac base. The amplitude of the excursion was also reduced at the apex, suggesting the systolic twist of the ventricular wall. The excursion of the apex in HCM was 0.6 +/- 1.7, 1.5 +/- 1.8 and 2.5 +/- 1.4 cm, respectively, toward the base of the heart as in the normal subjects. The maximum speeds of these motions were 34.0 +/- 9.2 cm/sec leftward, caudally and anteriory at the anterior-basal point and 36.2 +/- 7.3 cm/sec rightward, caudally and posteriorly in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular dysfunction in ischemic heart disease: fundamental importance of the fibrous matrix.

PubMed

Swan, H J

1994-05-01

The contractile function of the myocardium is coordinated by a fibrous matrix of exquisite organization and complexity. In the normal heart, and apparently in physiological hypertrophy, this matrix is submicroscopic. In pathological states changes are frequent, and usually progressive. Thickening of the many elements of the fine structure is due to an increased synthesis of Type I collagen, This change, which affects the myocardium in a global manner, can be observed by light microscopy using special techniques. Perivascular fibrosis, with an increase in vascular smooth muscle, is accompanied by development of fibrous septa, with a decrease in diastolic compliance. These structural changes are believed to be due to increased activation of the renin-angiotensin-aldosterone system, and to be independent of the processes of myocyte hypertrophy. Reparative or replacement fibrosis is a separate process by means of which small and large areas of necrosis heal, with the development of coarse collagen structures, which lack a specific organizational pattern. Regarding ischemic heart disease, an increase in tissue collagenase is found in experimental myocardial "stunning" and in the very early phase of acute infarction. Absence of elements of the fibrous matrix allow for myocyte slippage, and--if the affected area is large--cardiac dilatation. If, subsequently, the necrosis becomes transmural, there is further disturbance of collagen due to both mechanical strain and continued autolysis, During healing collagen synthesis increases greatly to allow for reparative scarring in the available tissue matrix. In cases of infarction with moderate or severe initial dilatation, pathological hypertrophy of the spared myocardium is progressive, accounting for late heart failure and poor survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Coordination of locomotor and cardiorespiratory networks of Lymnaea stagnalis by a pair of identified interneurones.

PubMed

Syed, N I; Winlow, W

1991-07-01

1. The morphology and electrophysiology of a newly identified bilateral pair of interneurones in the central nervous system of the pulmonate pond snail Lymnaea stagnalis is described. 2. These interneurones, identified as left and right pedal dorsal 11 (L/RPeD11), are electrically coupled to each other as well as to a large number of foot and body wall motoneurones, forming a fast-acting neural network which coordinates the activities of foot and body wall muscles. 3. The left and right sides of the body wall of Lymnaea are innervated by left and right cerebral A cluster neurones. Although these motoneurones have only ipsilateral projections, they are indirectly electrically coupled to their contralateral homologues via their connections with L/RPeD11. Similarly, the activities of left and right pedal G cluster neurones, which are known to be involved in locomotion, are also coordinated by L/RPeD11. 4. Selective ablation of both neurones PeD11 results in the loss of coordination between the bilateral cerebral A clusters. 5. Interneurones L/RPeD11 are multifunctional. In addition to coordinating motoneuronal activity, they make chemical excitatory connections with heart motoneurones. They also synapse upon respiratory motoneurones, hyperpolarizing those involved in pneumostome opening (expiration) and depolarizing those involved in pneumostome closure (inspiration). 6. An identified respiratory interneurone involved in pneumostome closure (visceral dorsal 4) inhibits L/RPeD11 together with all their electrically coupled follower cells. 7. Both L/RPeD11 have strong excitatory effects on another pair of electrically coupled neurones, visceral dorsal 1 and right parietal dorsal 2, which have previously been shown to be sensitive to changes in the partial pressure of environmental oxygen (PO2). 8. Although L/RPeD11 participate in whole-body withdrawal responses, electrical stimulation applied directly to these neurones was not sufficient to induce this behaviour.

The “Tail” of Connexin43: An Unexpected Journey from Alternative Translation to Trafficking

PubMed Central

Basheer, Wassim; Shaw, Robin

2015-01-01

With each heartbeat, Connexin43 (Cx43) cell-cell communication gap junctions are needed to rapidly spread and coordinate excitation signals for an effective heart contraction. The correct formation and delivery of channels to their respective membrane subdomain is referred to as protein trafficking. Altered Cx43 trafficking is a dangerous complication of diseased myocardium which contributes to the arrhythmias of sudden cardiac death. Cx43 has also been found to regulate many other cellular processes that cannot be explained by cell-cell communication. We recently identified the existence of up to six endogenous internally translated Cx43 N-terminal truncated isoforms from the same full-length mRNA molecule. This is the first evidence that alternative translation is possible for human ion channels and in human heart. Interestingly, we found that these internally translated isoforms, more specifically the 20 kDa isoform (GJA1-20k), is important for delivery of Cx43 to its respective membrane subdomain. This review covers recent advances in Cx43 trafficking and potential importance of alternatively translated Cx43 truncated isoforms. PMID:26526689

Team training for safer birth.

PubMed

Cornthwaite, Katie; Alvarez, Mary; Siassakos, Dimitrios

2015-11-01

Effective and coordinated teamworking is key to achieving safe birth for mothers and babies. Confidential enquiries have repeatedly identified deficiencies in teamwork as factors contributing to poor maternal and neonatal outcomes. The ingredients of a successful multi-professional team are varied, but research has identified some fundamental teamwork behaviours, with good communication, proficient leadership and situational awareness at the heart. Simple, evidence-based methods in teamwork training can be seamlessly integrated into a core, mandatory obstetric emergency training. Training should be an enjoyable, inclusive and beneficial experience for members of staff. Training in teamwork can lead to improved clinical outcomes and better birth experience for women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2

PubMed Central

Bylund, Jeffery B.; Trinh, Linh T.; Awgulewitsch, Cassandra P.; Paik, David T.; Jetter, Christopher; Jha, Rajneesh; Zhang, Jianhua; Nolan, Kristof; Xu, Chunhui; Thompson, Thomas B.; Kamp, Timothy J.

2017-01-01

Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling. PMID:28125926

Attention deficit disorders--drugs or nutrition?

PubMed

Matsudaira, Toshiko

2007-01-01

3-9% of schoolchildren in the U.K. suffer Attention Deficit and Hyperactivity Disorder (ADHD). Since the 1950s stimulants have been used. particularly methylphenidate and dextroamphetamine, with some 75% response rate. The first non-stimulant medication--atmoxetine hydrochloride, has also been used. However, side effects have included: growth retardation; appetite loss: headache: stomachache: heart problem: insomnia: seizure; change of character: addiction or even suicidal thoughts. Alternative treatments have been used including omega-3s, yet the way they benefit in ADHD is uncertain. They may be important in remodelling dendrites and synapses, and/or sustaining: blood brain barrier, neuronal membrane. neurotransmitter channel, receptors and ion channel. Stevens in 2003 found long-chain polyunsaturated fatty acids (LCPUFAs) effective for oppositional defiant disorder, whereas Eicosapentaenoic acid (EPA) specifically was helpful with disruptive behaviour. Docosahexaenoic acid (DHA) is important during gestation and early infancy, particularly for neurodevelopment. The Durham Trial by Richardson published in 2005, tested omega-3s with omega-6s on schoolchildren with developmental coordination disorder (many of them had ADHD symptoms), improving scores in co-ordination and short term memory.

Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2.

PubMed

Bylund, Jeffery B; Trinh, Linh T; Awgulewitsch, Cassandra P; Paik, David T; Jetter, Christopher; Jha, Rajneesh; Zhang, Jianhua; Nolan, Kristof; Xu, Chunhui; Thompson, Thomas B; Kamp, Timothy J; Hatzopoulos, Antonis K

2017-05-01

Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling.

SIRT3 mediates multi-tissue coupling for metabolic fuel switching.

PubMed

Dittenhafer-Reed, Kristin E; Richards, Alicia L; Fan, Jing; Smallegan, Michael J; Fotuhi Siahpirani, Alireza; Kemmerer, Zachary A; Prolla, Tomas A; Roy, Sushmita; Coon, Joshua J; Denu, John M

2015-04-07

SIRT3 is a member of the Sirtuin family of NAD(+)-dependent deacylases and plays a critical role in metabolic regulation. Organism-wide SIRT3 loss manifests in metabolic alterations; however, the coordinating role of SIRT3 among metabolically distinct tissues is unknown. Using multi-tissue quantitative proteomics comparing fasted wild-type mice to mice lacking SIRT3, innovative bioinformatic analysis, and biochemical validation, we provide a comprehensive view of mitochondrial acetylation and SIRT3 function. We find SIRT3 regulates the acetyl-proteome in core mitochondrial processes common to brain, heart, kidney, liver, and skeletal muscle, but differentially regulates metabolic pathways in fuel-producing and fuel-utilizing tissues. We propose an additional maintenance function for SIRT3 in liver and kidney where SIRT3 expression is elevated to reduce the acetate load on mitochondrial proteins. We provide evidence that SIRT3 impacts ketone body utilization in the brain and reveal a pivotal role for SIRT3 in the coordination between tissues required for metabolic homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Heart Repair and Regeneration: Recent Insights from Zebrafish Studies

PubMed Central

Lien, Ching-Ling; Harrison, Michael R.; Tuan, Tai-Lan; Starnes, Vaughn A

2012-01-01

Cardiovascular disease is the leading cause of death in United States and worldwide. Failure to properly repair or regenerate damaged cardiac tissues after myocardial infarction is a major cause of heart failure. In contrast to humans and other mammals, zebrafish hearts regenerate after substantial injury or tissue damage. Here, we review recent progress in studying zebrafish heart regeneration, addressing the molecular and cellular responses in the three tissue layers of the heart: myocardium, epicardium, and endocardium. We also compare different injury models utilized to study zebrafish heart regeneration, and discuss the differences in responses to injury between mammalian and zebrafish hearts. By learning how zebrafish hearts regenerate naturally, we can better design therapeutic strategies for repairing human hearts after myocardial infarction. PMID:22818295

Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

NASA Astrophysics Data System (ADS)

Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

2014-03-01

Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

Plasma microvesicle analysis identifies microRNA 129-5p as a biomarker of heart failure in univentricular heart disease.

PubMed

Ramachandran, Sweta; Lowenthal, Alexander; Ritner, Carissa; Lowenthal, Shiri; Bernstein, Harold S

2017-01-01

Biomarkers of heart failure in adults have been extensively studied. However, biomarkers to monitor the progression of heart failure in children with univentricular physiology are less well understood. We proposed that as mediators of diverse pathophysiology, miRNAs contained within circulating microvesicles could serve as biomarkers for the presence and progression of heart failure in univentricular patients. To test this, we studied the association of heart failure with elevations in specific miRNAs isolated from circulating microvesicles in a cohort of children with univentricular heart disease and heart failure. We conducted a single site cross-sectional observational study of 71 children aged 1 month-7 years with univentricular heart disease and heart failure. We demonstrated that levels of miR129-5p isolated from plasma microvesicles were inversely related to the degree of clinical heart failure as assessed by Ross score. We then showed that miR129-5p levels are downregulated in HL1 cells and human embryonic stem cell-derived cardiomyocytes exposed to oxidative stress. We demonstrated that bone morphogenetic protein receptor 2, which has been implicated in the development of pulmonary vascular disease, is a target of miR129-5p, and conversely regulated in response to oxidative stress in cell culture. Levels of miR129-5p were inversely related to the degree of clinical heart failure in patients with univentricular heart disease. This study demonstrates that miR129-5p is a sensitive and specific biomarker for heart failure in univentricular heart disease independent of ventricular morphology or stage of palliation. Further study is warranted to understand the targets affected by miR129-5p with the development of heart failure in patients with univentricular physiology.

The SPURS Data Management System: Real-time Situational Awareness at Sea

NASA Astrophysics Data System (ADS)

Bingham, F.; Chao, Y.; Li, P.; Vu, Q. A.

2012-12-01

SPURS (Salinity Processes in the Upper ocean Regional Study) is a field program in the North Atlantic to study the subtropical surface salinity maximum. It is a heterogeneous array consisting of research ships, profiling floats, surface drifters, gliders, microstructure profilers and moorings, as well as satellite observations and models. The SPURS Data Management System aims to capture the status of the observing system in near-real time and allow SPURS science team members to deploy observational assets "on the fly". At the heart of this is a visualization system that tracks the positions of the various assets and displays them in a an interface using Google Earth. The interface was used by program participants on land and at sea to coordinate the deployment of instrumentation. Before the Fall AGU, SPURS will have completed the first part of its mission with a 6-week cruise to the study area. This poster presents some of the highlights of the field campaign, and details the lessons learned in doing real-time oceanography on the high seas.

Xenopus: An Emerging Model for Studying Congenital Heart Disease

PubMed Central

Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

2011-01-01

Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome.

PubMed

An, Meng-Yao; Sun, Kai; Li, Yan; Pan, Ying-Ying; Yin, Yong-Qiang; Kang, Yi; Sun, Tao; Wu, Hong; Gao, Wei-Zhen; Lou, Jian-Shi

2018-03-01

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH 2 CH 2 CH 2 SO 3 )2· H 2 O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 μmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD 50 ) and 90% repolarization (APD 90 ), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (I Ks ), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC 50 value of 201.1 μmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, I Ks , thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability.

PubMed

Jennings, J Richard; Sheu, Lei K; Kuan, Dora C-H; Manuck, Stephen B; Gianaros, Peter J

2016-04-01

Resting high-frequency heart rate variability (HF-HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF-HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes-open, 5-min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF-HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF-HRV. However, HF-HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF-HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF-HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment. © 2015 Society for Psychophysiological Research.

Human nutrition and food research: opportunities and challenges in the post-genomic era.

PubMed Central

Fairweather-Tait, Susan J

2003-01-01

Sequencing of the human genome has opened the door to the most exciting new era for nutritional science. It is now possible to study the underlying mechanisms for diet-health relationships, and in the near future dietary advice (and possibly tailored food products) for promoting optimal health could be provided on an individual basis, in relation to genotype and lifestyle. The role of food in human evolution is briefly reviewed, from palaeolithic times to modern-day hunter-gatherer societies. The aetiology of 'diseases of modern civilization', such as diabetes, heart disease and cancer, and the effect of changes in dietary patterns are discussed. The risk of disease is often associated with common single nucleotide polymorphisms, but the effect is dependent on dietary intake and nutritional status, and is often more apparent in intervention studies employing a metabolic challenge. To understand the link between diet and health, nutritional research must cover a broad range of areas, from molecular to whole body studies, and is an excellent example of integrative biology, requiring a systems biology approach. The annual cost to the National Health Service of diet-related diseases is estimated to be in excess of 15 billion, and although diet is a key component of any preventative strategy, it is not given the prominence it deserves. For example, less than 1% of the pound 1.6 billion budget for coronary heart disease is spent on prevention. The polygenic and multifactorial nature of chronic diseases requires substantial resources but the potential rewards, in terms of quality of life and economics, are enormous. It is timely therefore to consider investing in a long-term coordinated national programme for nutrition research, combining nutritional genomics with established approaches, to improve the health of individuals and of the nation. PMID:14561328

The Neural Network In Coordinate Transformation

NASA Astrophysics Data System (ADS)

Urusan, Ahmet Yucel

2011-12-01

In international literature, Coordinate operations is divided into two categories. They are coordinate conversion and coordinate transformation. Coordinates converted from coordinate system A to coordinate system B in the same datum (mean origine, scale and axis directions are same) by coordinate conversion. There are two different datum in coordinate transformation. The basis of each datum to a different coordinate reference system. In Coordinate transformation, coordinates are transformed from coordinate reference system A to coordinate referance system B. Geodetic studies based on physical measurements. Coordinate transformation needs identical points which were measured in each coordinate reference system (A and B). However it is difficult (and need a big reserved budget) to measure in some places like as top of mountain, boundry of countries and seaside. In this study, this sample problem solution was researched. The method of learning which is one of the neural network methods, was used for solution of this problem.

A protocol to study ex vivo mouse working heart at human-like heart rate.

PubMed

Feng, Han-Zhong; Jin, Jian-Ping

2018-01-01

Genetically modified mice are widely used as experimental models to study human heart function and diseases. However, the fast rate of normal mouse heart at 400-600bpm limits its capacity of assessing kinetic parameters that are important for the physiology and pathophysiology of human heart that beats at a much slower rate (75-180bpm). To extend the value of mouse models, we established a protocol to study ex vivo mouse working hearts at a human-like heart rate. In the presence of 300μM lidocaine to lower pacemaker and conductive activities and prevent arrhythmia, a stable rate of 120-130bpm at 37°C is achieved for ex vivo mouse working hearts. The negative effects of decreased heart rate on force-frequency dependence and lidocaine as a myocardial depressant on intracellular calcium can be compensated by using a higher but still physiological level of calcium (2.75mM) in the perfusion media. Multiple parameters were studied to compare the function at the human-like heart rate with that of ex vivo mouse working hearts at the standard rate of 480bpm. The results showed that the conditions for slower heart rate in the presence of 300μM lidocaine did not have depressing effect on left ventricular pressure development, systolic and diastolic velocities and stroke volume with maintained positive inotropic and lusitropic responses to β-adrenergic stimulation. Compared with that at 480bpm, the human-like heart rate increased ventricular filling and end diastolic volume with enhanced Frank-Starling responses. Coronary perfusion was increased from longer relaxation time and interval between beats whereas cardiac efficiency was significantly improved. Although the intrinsic differences between mouse and human heart remain, this methodology for ex vivo mouse hearts to work at human-like heart rate extends the value of using genetically modified mouse models to study cardiac function and human heart diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Not just another Wii training": a graded Wii protocol to increase physical fitness in adolescent girls with probable developmental coordination disorder-a pilot study.

PubMed

Bonney, Emmanuel; Rameckers, Eugene; Ferguson, Gillian; Smits-Engelsman, Bouwien

2018-02-22

Adolescents with low motor competence participate less in physical activity and tend to exhibit decreased physical fitness compared to their peers with high motor competence. It is therefore essential to identify new methods of enhancing physical fitness in this population. Active video games (AVG) have been shown to improve motor performance, yet investigations of its impact on physical fitness are limited. The objective of this study was to examine the impact of the graded Wii protocol in adolescent girls with probable Developmental Coordination Disorder (p-DCD). A single-group pre-post design was conducted to assess the impact of a newly developed Wii protocol in adolescent girls attending school in a low income community of Cape Town, South Africa. Sixteen participants (aged 13-16 years) with p-DCD (≤16th percentile on the MABC-2 test) were recruited. Participants received 45 min Wii training for 14 weeks. Outcome measures included the six-minute walk distance and repeated sprint ability. Information on heart rate, enjoyment and perceived exertion ratings were also collected. Significant improvements in aerobic and anaerobic fitness were observed. The participants reported high enjoyment scores and low perceived exertion ratings. The graded Wii protocol was easily adaptable and required little resources (space, equipment and expertise) to administer. The findings provide preliminary evidence to support the use of the graded Wii protocol for promoting physical fitness in adolescent girls with p-DCD. Further studies are needed to confirm these results and to validate the clinical efficacy of the protocol in a larger sample with a more robust design.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

PubMed

Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

2017-05-01

Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

Effect of uterine contractions on fetal heart rate in pregnancy: a prospective observational study.

PubMed

Sletten, Julie; Kiserud, Torvid; Kessler, Jörg

2016-10-01

The new Holter monitoring technology enables long-term electrocardiographic recording of the fetal heart rate without discomfort for the mother. The aim of the study was to assess the feasibility of a fetal Holter monitor. This technology was further used to study fetal heart rate outside the hospital setting during normal daily activities and to test the hypothesis that uterine activity during pregnancy influences fetal heart rate. Prospective observational study including 12 healthy pregnant women at 20-40 weeks of gestation. Data were collected using the Monica AN24 system. Outcome measures were fetal heart rate, maternal heart rate, and uterine activity categorized according to the strength of the electrohysterographic signal. The recordings had a median length of 18.8 h, and fetal heart rate and maternal heart rate were obtained with success rates of 73.1 and 99.9%, respectively. Uterine activity was found to affect fetal heart rate in all participants. Compared with the basal tone and mild levels of uterine activity, moderate and strong levels of uterine activity were associated with increases in fetal heart rate of 4.0 and 5.7 beats/min, respectively. At night, the corresponding increases were 4.9 and 7.6 beats/min. Linear correlations were found between maternal heart rate and fetal heart rate in 11 of the 12 cases, with a mean coefficient beta of 0.189. Both maternal heart rate and fetal heart rate exhibited a diurnal pattern, with lower heart rates being recorded at night. Uterine activity during pregnancy is associated with a graded response in fetal heart rate and may represent a physiological challenge for the development and adaptation of the fetal cardiovascular system. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Long‐term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study

PubMed Central

Ho, Jennifer E.; Larson, Martin G.; Ghorbani, Anahita; Cheng, Susan; Coglianese, Erin E.; Vasan, Ramachandran S.; Wang, Thomas J.

2014-01-01

Background Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow‐up. Methods and Results Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all‐cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions Individuals with a higher heart rate are at elevated long‐term risk for cardiovascular events, in particular, heart failure, and all‐cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation. PMID:24811610

Effects of short-term exposure to powerline-frequency electromagnetic field on the electrical activity of the heart.

PubMed

Elmas, Onur; Comlekci, Selcuk; Koylu, Halis

2012-01-01

ABSTRACT The heart is a contractile organ that can generate its own rhythm. The contraction, or the rhythm, of the heart may be influenced by electromagnetic field (EMF) exposure, because of the heart's excitability characteristic. In previous studies, different methods have been used to study the possible effects of an extremely low frequency electromagnetic field (ELF-EMF) on the heart. But the studies' designs were not similar, and the results were also different. Recent studies have shown some evidence that short-term EMF exposure can influence the heart more than long-term exposure. This study investigated how the heart is affected in the first EMF exposure. In a simulation of the daily exposure of humans to a power frequency, Wistar albino rats were used. By utilizing the Helmholtz-coil set, we obtained a 50-Hz, 1-μT EMF and examined rat heart activity during short-term EMF exposure. No effect was observed under this exposure condition. The results obtained do not confirm a possible mechanism in the electrical activity of the rat heart model.

Cost-of-illness studies in heart failure: a systematic review 2004-2016.

PubMed

Lesyuk, Wladimir; Kriza, Christine; Kolominsky-Rabas, Peter

2018-05-02

Heart failure is a major and growing medical and economic problem worldwide as 1-2% of the healthcare budget are spent for heart failure. The prevalence of heart failure has increased over the past decades and it is expected that there will be further raise due to the higher proportion of elderly in the western societies. In this context cost-of-illness studies can significantly contribute to a better understanding of the drivers and problems which lead to the increasing costs in heart failure. The aim of this study was to perform a systematic review of published cost-of-illness studies related to heart failure to highlight the increasing cost impact of heart failure. A systematic review was conducted from 2004 to 2016 to identify cost-of-illness studies related to heart failure, searching PubMed (Medline), Cochrane, Science Direct (Embase), Scopus and CRD York Database. Of the total of 16 studies identified, 11 studies reported prevalence-based estimates, 2 studies focused on incidence-based data and 3 articles presented both types of cost data. A large variation concerning cost components and estimates can be noted. Only three studies estimated indirect costs. Most of the included studies have shown that the costs for hospital admission are the most expensive cost element. Estimates for annual prevalence-based costs for heart failure patients range from $868 for South Korea to $25,532 for Germany. The lifetime costs for heart failure patients have been estimated to $126.819 per patient. Our review highlights the considerable and growing economic burden of heart failure on the health care systems. The cost-of-illness studies included in this review show large variations in methodology used and the cost results vary consequently. High quality data from cost-of-illness studies with a robust methodology applied can inform policy makers about the major cost drivers of heart failure and can be used as the basis of further economic evaluations.

Effective components of nurse-coordinated care to prevent recurrent coronary events: a systematic review and meta-analysis.

PubMed

Snaterse, Marjolein; Dobber, Jos; Jepma, Patricia; Peters, Ron J G; Ter Riet, Gerben; Boekholdt, S Matthijs; Buurman, Bianca M; Scholte op Reimer, Wilma J M

2016-01-01

Current guidelines on secondary prevention of cardiovascular disease recommend nurse-coordinated care (NCC) as an effective intervention. However, NCC programmes differ widely and the efficacy of NCC components has not been studied. To investigate the efficacy of NCC and its components in secondary prevention of coronary heart disease by means of a systematic review and meta-analysis of randomised controlled trials. 18 randomised trials (11 195 patients in total) using 15 components of NCC met the predefined inclusion criteria. These components were placed into three main intervention strategies: (1) risk factor management (13 studies); (2) multidisciplinary consultation (11 studies) and (3) shared decision making (10 studies). Six trials combined NCC components from all three strategies. In total, 30 outcomes were observed. We summarised observed outcomes in four outcome categories: (1) risk factor levels (16 studies); (2) clinical events (7 studies); (3) patient-perceived health (7 studies) and (4) guideline adherence (3 studies). Compared with usual care, NCC lowered systolic blood pressure (weighted mean difference (WMD) 2.96 mm Hg; 95% CI 1.53 to 4.40 mm Hg) and low-density lipoprotein cholesterol (WMD 0.23 mmol/L; 95% CI 0.10 to 0.36 mmol/L). NCC also improved smoking cessation rates by 25% (risk ratio 1.25; 95% CI 1.08 to 1.43). NCC demonstrated to have an effect on a small number of outcomes. NCC that incorporated blood pressure monitoring, cholesterol control and smoking cessation has an impact on the improvement of secondary prevention. Additionally, NCC is a heterogeneous concept. A shared definition of NCC may facilitate better comparisons of NCC content and outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Assessment of deformation of the mitral valve complex during off-pump coronary artery bypass surgery using three-dimensional echocardiography in a porcine model.

PubMed

Igarashi, Takashi; Iwai-Takano, Masumi; Wakamatsu, Hiroki; Haruta, Mineyuki; Omata, Sadao; Yokoyama, Hitoshi

2018-01-01

This study aimed to assess the deformation of the mitral valve complex during the displacement of the beating heart by using three-dimensional echocardiography in a porcine off-pump coronary artery bypass grafting (OPCAB) model. In nine healthy swine, we positioned the beating heart as an OPCAB model, i.e. control, left anterior descending artery (LAD), right coronary artery (RCA), and left circumflex artery (LCX) positions. In each position, three-dimensional echocardiography was performed to assess the mitral valve complex with hemodynamic parameters. We analyzed the deformation of the mitral valve and the three-dimensional coordinates of the papillary muscles. There was a significant increase in maximum tenting length and tenting volume (control 0.70±0.30, LAD 0.65±0.27, RCA 0.79±0.23, LCX 0.95±0.34cm 3 , p<0.05) in the LCX position compared with the other positions. The posterior papillary muscle (PPM) angle had a significant relationship with the tenting volume (r=-0.643, p<0.001). The PPM was displaced to the medial side in the LAD and LCX positions (p<0.01). The prime cause of the deformation of the mitral leaflets is suggested to be the displacement of the PPM associated with the change in geometry of the left ventricle in a porcine model. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Ablation of RIC8A function in mouse neurons leads to a severe neuromuscular phenotype and postnatal death.

PubMed

Ruisu, Katrin; Kask, Keiu; Meier, Riho; Saare, Merly; Raid, Raivo; Veraksitš, Alar; Karis, Alar; Tõnissoo, Tambet; Pooga, Margus

2013-01-01

Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide exchange factor required for the intracellular regulation of G protein signalling. RIC8 activates different Gα subunits via non-canonical pathway, thereby amplifying and prolonging the G protein mediated signal. In order to circumvent the embryonic lethality associated with the absence of RIC8A and to study its role in the nervous system, we constructed Ric8a conditional knockout mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a (F/F) ) background ablated RIC8A function in most differentiated neuron populations. Mutant SynCre (+/-) Ric8 (lacZ/F) mice were born at expected Mendelian ratio, but they died in early postnatal age (P4-P6). The mutants exhibited major developmental defects, like growth retardation and muscular weakness, impaired coordination and balance, muscular spasms and abnormal heart beat. Histological analysis revealed that the deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced. However, we did not observe gross morphological changes in brains of SynCre (+/-) Ric8a (lacZ/F) mutants. Our results demonstrate that in mice the activity of RIC8A in neurons is essential for survival and its deficiency causes a severe neuromuscular phenotype.

Ablation of RIC8A Function in Mouse Neurons Leads to a Severe Neuromuscular Phenotype and Postnatal Death

PubMed Central

Ruisu, Katrin; Kask, Keiu; Meier, Riho; Saare, Merly; Raid, Raivo; Veraksitš, Alar; Karis, Alar; Tõnissoo, Tambet; Pooga, Margus

2013-01-01

Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide exchange factor required for the intracellular regulation of G protein signalling. RIC8 activates different Gα subunits via non-canonical pathway, thereby amplifying and prolonging the G protein mediated signal. In order to circumvent the embryonic lethality associated with the absence of RIC8A and to study its role in the nervous system, we constructed Ric8a conditional knockout mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a F/F) background ablated RIC8A function in most differentiated neuron populations. Mutant SynCre +/- Ric8 lacZ/F mice were born at expected Mendelian ratio, but they died in early postnatal age (P4-P6). The mutants exhibited major developmental defects, like growth retardation and muscular weakness, impaired coordination and balance, muscular spasms and abnormal heart beat. Histological analysis revealed that the deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced. However, we did not observe gross morphological changes in brains of SynCre +/- Ric8a lacZ/F mutants. Our results demonstrate that in mice the activity of RIC8A in neurons is essential for survival and its deficiency causes a severe neuromuscular phenotype. PMID:23977396

Exploration of patients' readiness for an eHealth management program for chronic heart failure: a preliminary study.

PubMed

Nahm, Eun-Shim; Blum, Kay; Scharf, Barbara; Friedmann, Erika; Thomas, Sue; Jones, Deborah; Gottlieb, Stephen S

2008-01-01

Heart failure (HF) is a major public health problem in the United States. Approximately 5 million Americans are living with HF, and each year, 550,000 more are newly diagnosed. With recent, rapidly advancing technologies, many studies have examined the effects of technology-based HF management programs. Most of these studies focused on telemonitoring devices, lacking an aspect to motivate individuals to manage their own illnesses. This exploratory study was conducted to (1) examine the readiness of patients with HF in using an eHealth program that includes both telemonitoring and motivational components (ie, Web learning modules, eCommunication) and (2) assess the specific needs of patients with HF that can be addressed by a future eHealth program. This was a single group descriptive study using a convenience sample. A total of 44 patients with HF (mean age, 72.8 years; range, 55-85 years) were recruited from the pool of enrollees of the Medicare Coordinated Care Demonstration project for HF management that used only a telemonitoring component. Although only 10 participants were users, among 34 nonusers, 17 reported availability of Web access, and 15 reported that they would use the Internet if access and training were available. Overall, confidence for using telemonitoring devices and Web-based health modules was high, with means of 27 (range, 3-30) and 7.6 (range, 1-10), respectively. Confidence for learning health information using Web modules, however, was lower with a mean of 41.5 (range, 8-80). The 2 most highly rated health information needs were research findings (n = 41, 93.2%) and medication (n = 39, 88.6%). Most participants would like to have e-mail communication with healthcare providers. The findings showed the participants' high readiness to use the proposed eHealth program if access and training were provided. This study used a small convenience sample. Further studies are needed with larger, diverse samples.

Effect of heart rate on the hemodynamics of bileaflet mechanical heart valves' prostheses (St. Jude Medical) in the aortic position and in the opening phase: A computational study.

PubMed

Jahandardoost, Mehdi; Fradet, Guy; Mohammadi, Hadi

2016-03-01

To date, to the best of the authors' knowledge, in almost all of the studies performed around the hemodynamics of bileaflet mechanical heart valves, a heart rate of 70-72 beats/min has been considered. In fact, the heart rate of ~72 beats/min does not represent the entire normal physiological conditions under which the aortic or prosthetic valves function. The heart rates of 120 or 50 beats/min may lead to hemodynamic complications, such as plaque formation and/or thromboembolism in patients. In this study, the hemodynamic performance of the bileaflet mechanical heart valves in a wide range of normal and physiological heart rates, that is, 60-150 beats/min, was studied in the opening phase. The model considered in this study was a St. Jude Medical bileaflet mechanical heart valve with the inner diameter of 27 mm in the aortic position. The hemodynamics of the native valve and the St. Jude Medical valve were studied in a variety of heart rates in the opening phase and the results were carefully compared. The results indicate that peak values of the velocity profile downstream of the valve increase as heart rate increases, as well as the location of the maximum velocity changes with heart rate in the St. Jude Medical valve model. Also, the maximum values of shear stress and wall shear stresses downstream of the valve are proportional to heart rate in both models. Interestingly, the maximum shear stress and wall shear stress values in both models are in the same range when heart rate is <90 beats/min; however, these values significantly increase in the St. Jude Medical valve model when heart rate is >90 beats/min (up to ~40% growth compared to that of the native valve). The findings of this study may be of importance in the hemodynamic performance of bileaflet mechanical heart valves. They may also play an important role in design improvement of conventional prosthetic heart valves and the design of the next generation of prosthetic valves, such as percutaneous valves. © IMechE 2016.

ACCF/AHA/HFSA 2011 survey results: current staffing profile of heart failure programs, including programs that perform heart transplant and mechanical circulatory support device implantation.

PubMed

Jessup, Mariell; Albert, Nancy M; Lanfear, David E; Lindenfeld, JoAnn; Massie, Barry M; Walsh, Mary Norine; Zucker, Mark J

2011-05-01

There have been no published recommendations about staffing needs for a heart failure (HF) clinic or an office setting focused on heart transplant. The goal of this survey was to understand the current staffing environment of HF, transplant, and mechanical circulatory support device (MCSD) programs in the United States and abroad. This report identifies current staffing patterns but does not endorse a particular staffing model. An online survey, jointly sponsored by the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), and the Heart Failure Society of America (HFSA), was sent to the members of all 3 organizations who had identified themselves as interested in HF, heart transplant, or both, between March 12, 2009, and May 12, 2009. The overall response rate to the 1,823 e-mail surveys was 23%. There were 257 unique practices in the United States (81% of total sites) and 58 international sites (19%); approximately 30% of centers were in a cardiovascular group practice and 30% in a medical school hospital setting. The large majority of practices delivered HF care in both an inpatient and outpatient environment, and slightly more centers were implanting MCSDs (47%) than performing cardiac transplantation (39%). Most practices (43%) were small, with <4 staff members, or small- to medium-sized (34%), with 4 to 10 staff members, with only 23% being medium (11-20 staff) or large programs (>20 staff). On average, a U.S. HF practice cared for 1,641 outpatients annually. An average HF program with transplant performed 10 transplants. Although larger programs were able to perform more transplants and see more outpatient HF visits, their clinician staffing volume tended to double for approximately every 500 to 700 additional HF visits annually. The average staffing utilization was 2.65 physician full-time equivalents (FTEs), 2.21 nonphysician practitioner (nurse practitioner or physician assistant) FTEs, and 2.61 nurse coordinator FTEs annually. The HF patient population is growing in number in the United States and internationally, and the clinicians who provide the highly skilled and time-consuming care to this population are under intense scrutiny as a result of focused quality improvement initiatives and reduced financial resources. Staffing guidelines should be developed to ensure that an adequate number of qualified professionals are hired for a given practice volume. These survey results are an initial step in developing such standards. Copyright © 2011. Published by Elsevier Inc.

Physical demands in working life and individual physical capacity.

PubMed

Karlqvist, L; Leijon, O; Härenstam, A

2003-08-01

The purpose of this study was to investigate the prevalence of the excess of metabolic level (metabolic demands in work exceeding one-third of the individual's aerobic capacity) of working men and women today and to describe the population whose metabolic level is exceeded. A second aim was to explore how externally assessed metabolic demands match with the physical function and capacity of working men and women in jobs with the lowest and the highest demands. The aerobic power of each individual (94 men and 94 women) was estimated from heart rate and workload in sub-maximal tests from dynamic legwork on a cycle ergometer. Physical activity was assessed using a task-oriented interview technique. Physical function was measured by tests of muscle endurance in arms, abdomen and legs, handgrip pressure, balance and coordination. The calculation of individual metabolic demands during a "typical working day" showed that 27% of the men and 22% of the women exceeded their metabolic level. The results indicate that the physical fitness is low or somewhat low for two-thirds of the 94 men and for more than one-half of the 94 women. Women in the group with the highest job demands had significantly lower muscle endurance in the abdomen and legs and worse coordination than women in the group with the lowest job demands. Metabolic demands in working life today remain high. This is reflected in a mismatch between individual physical capacity and the physical demands of work for 25% of the population.

The Feasibility of Using the BrightHearts Biofeedback-Assisted Relaxation Application for the Management of Pediatric Procedural Pain: A Pilot Study.

PubMed

Burton, Karen L O; Morrow, Angela M; Beswick, Brooke V; Khut, George P

2018-04-17

The objective of this pilot study was to assess the acceptability and feasibility of using BrightHearts, a biofeedback-assisted relaxation application (app), in children undergoing painful procedures. Thirty children 7 to 18 years of age undergoing a medical procedure (peripheral blood collection, botulinum toxin injection, or intravenous cannula insertion) participated. Participants used BrightHearts, a heart rate-controlled biofeedback-assisted relaxation training app delivered via an iPad with heart rate measured through a pulse oximeter worn on the ear or thumb. Feasibility was assessed through observations and patient, parent/carer, and healthcare professional feedback. Patient, parent/carer, and healthcare professional satisfaction with BrightHearts was rated using investigator-developed surveys. Eighty-three percent of child participants reported that they found BrightHearts helpful during the procedure and that they would use BrightHearts again. All parents and 96% of healthcare professionals indicated they would use BrightHearts again. Sixty-four percent of healthcare providers perceived that BrightHearts assisted with the ease of performing the procedure. Qualitative analyses found 2 themes: (1) BrightHearts calms through providing distraction and biofeedback and (2) the impact of BrightHearts on the procedure. This pilot study demonstrates the feasibility of using biofeedback-assisted relaxation delivered via the BrightHearts app in children undergoing peripheral blood collection and cannulation. Future studies are required to evaluate BrightHearts' efficacy in reducing pain and anxiety during painful procedures and distinguish the effects of a biofeedback-mediated app from distraction. © 2018 World Institute of Pain.

Bomb blast imaging: bringing order to chaos.

PubMed

Dick, E A; Ballard, M; Alwan-Walker, H; Kashef, E; Batrick, N; Hettiaratchy, S; Moran, C G

2018-06-01

Blast injuries are complex, severe, and outside of our everyday clinical practice, but every radiologist needs to understand them. By their nature, bomb blasts are unpredictable and affect multiple victims, yet require an immediate, coordinated, and whole-hearted response from all members of the clinical team, including all radiology staff. This article will help you gain the requisite expertise in blast imaging including recognising primary, secondary, and tertiary blast injuries. It will also help you understand the fundamental role that imaging plays during mass casualty attacks and how to avoid radiology becoming a bottleneck to the forward flow of severely injured patients as they are triaged and treated. Copyright © 2018. Published by Elsevier Ltd.

Effects of coordinate system choice on measured regional myocardial function in short-axis cine electron-beam tomography

NASA Astrophysics Data System (ADS)

Reed, Judd E.; Rumberger, John A.; Buithieu, Jean; Behrenbeck, Thomas; Breen, Jerome F.; Sheedy, Patrick F., II

1995-05-01

Following myocardial infarction, the size of the infarcted region and the systolic functioning of the noninfarcted region are commonly assessed by various cross- sectional imaging techniques. A series of images representing successive phases of the cardiac cycle can be acquired by several imaging modalities including electron beam computed tomography, magnetic resonance imaging, and echocardiography. For the assessment of patterns of ventricular contraction, images are commonly acquired of ventricular cross-sections normal to the 'long' axis of the heart and parallel to the mitral valve plane. The endocardial and epicardial surfaces of the myocardium are identified. Then the ventricle is divided into sectors and the volumes of blood and myocardium within each sector at multiple phases of the cardiac cycle are measured. Regional function parameters are derived from these measurements. This generally mandates the use of a polar or cylindrical coordinate system. Various algorithms have been used to select the origin of this coordinate system. These include the centroid of the endocardial surface, the epicardial surface, or of a polygon whose vertices lie midway between the epicardial and endocardial surfaces of the myocardium (centerline method). Another algorithm has been developed in our laboratory. This uses the centroid (or center of mass) of the myocardium exclusive of the ventricular cavity. Each of these choices for origin of coordinate system can be derived from the end- diastolic image or from the end-systolic image. Alternately, new coordinate systems can be selected for each phase of the cardiac cycle. These are referred to as 'floating' coordinate systems. A series of computer models have been developed in our laboratory to study the effects of each of these choices on the regional function parameters of normal ventricles and how these choices effect the quantification of regional abnormalities after myocardial infarction. The most sophisticated of these is an interactive program with a graphical user interface which facilitates the simulation of a wide variety of dynamic ventricular cross sections. Analysis of these simulations has led to a better understanding of how polar coordinate system placement influences the results of quantitative regional ventricular function assessment. It has also created new insight into how the appropriateness of the placement of such a polar coordinate systems can be objectively assessed. The validity of the conclusions drawn from the analysis of simulated ventricular shapes was validated through the analysis of outlines extracted from cine electron beam computed tomographic images. This was done using another interactive software tool developed specifically for this purpose. With this tool, the effects on regional function parameters of various choices for origin placement can be directly observed. This has proven to reinforce the conclusions drawn from the simulations and has led to the modification of the procedures used in our laboratory. Conclusions: The so-called floating coordinate systems are superior to fixed ones for quantification of regional left ventricular contraction in almost every respect. The use of regional ejection fractions with a coordinate system origin located at the centroid of the endocardial surface can lead to 180 degree errors in identifying the location of a myocardial infarction. This problem is less pronounced with midline and epicardium- based centroids and does not occur when the centroid of the myocardium is used. The quantified migration of myocardial mass across sector boundaries is a useful indicator of an inappropriate choice of coordinate system origin. When the centroid of the myocardium falls well within the ventricular cavity, as it usually does, it is a better location for the origin for regional analysis than any of the other centroids analyzed.

77 FR 65001 - Proposed Collection; Comment Request: The Jackson Heart Study (JHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... Request: The Jackson Heart Study (JHS) SUMMARY: In compliance with the requirement of Section 3506(c)(2)(A... collection projects, the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health... and Budget (OMB) for review and approval. Proposed Collection: Title: The Jackson Heart Study: Annual...

75 FR 1789 - Proposed Collection; Comment Request; The Jackson Heart Study (JHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... Request; The Jackson Heart Study (JHS) Summary: In compliance with the requirement of Section 3506(c)(2)(A... collection projects, the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health... and Budget (OMB) for review and approval. Proposed Collection: Title: The Jackson Heart Study: Annual...

Do You Use Your Head or Follow Your Heart? Self-Location Predicts Personality, Emotion, Decision Making, and Performance

PubMed Central

Fetterman, Adam K.; Robinson, Michael D.

2013-01-01

The head is thought to be rational and cold, whereas the heart is thought to be emotional and warm. Eight studies (total N = 725) pursued the idea that such body metaphors are widely consequential. Study 1 introduced a novel individual difference variable, one asking people to locate the self in the head or the heart. Irrespective of sex differences, head-locators characterized themselves as rational, logical, and interpersonally cold, whereas heart-locators characterized themselves as emotional, feminine, and interpersonally warm (Studies 1–3). Study 4 found that head-locators were more accurate in answering general knowledge questions and had higher GPAs and Study 5 found that heart-locators were more likely to favor emotional over rational considerations in moral decision-making. Study 6 linked self-locations to reactivity phenomena in daily life –e.g., heart-locators experienced greater negative emotion on high stressor days. Study 7 manipulated attention to the head versus the heart and found that head-pointing facilitated intellectual performance, whereas heart-pointing led to emotional decision-making. Study 8 replicated Study 3’s findings with a nearly year-long delay between the self-location and outcome measures. The findings converge on the importance of head-heart metaphors for understanding individual differences in cognition, emotion, and performance. PMID:23773045

Do you use your head or follow your heart? Self-location predicts personality, emotion, decision making, and performance.

PubMed

Fetterman, Adam K; Robinson, Michael D

2013-08-01

The head is thought to be rational and cold, whereas the heart is thought to be emotional and warm. In 8 studies (total N = 725), we pursued the idea that such body metaphors are widely consequential. Study 1 introduced a novel individual difference variable, one asking people to locate the self in the head or the heart. Irrespective of sex differences, head-locators characterized themselves as rational, logical, and interpersonally cold, whereas heart-locators characterized themselves as emotional, feminine, and interpersonally warm (Studies 1-3). Study 4 showed that head-locators were more accurate in answering general knowledge questions and had higher grade point averages, and Study 5 showed that heart-locators were more likely to favor emotional over rational considerations in moral decision making. Study 6 linked self-locations to reactivity phenomena in daily life--for example, heart-locators experienced greater negative emotion on high stressor days. In Study 7, we manipulated attention to the head versus the heart and found that head-pointing facilitated intellectual performance, whereas heart-pointing led to emotional decision making. Study 8 replicated Study 3's findings with a nearly year-long delay between the self-location and outcome measures. The findings converge on the importance of head-heart metaphors for understanding individual differences in cognition, emotion, and performance.

Cardiorespiratory Coordination in Repeated Maximal Exercise

PubMed Central

Garcia-Retortillo, Sergi; Javierre, Casimiro; Hristovski, Robert; Ventura, Josep L.; Balagué, Natàlia

2017-01-01

Increases in cardiorespiratory coordination (CRC) after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate) was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1) were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax), maximal oxygen consumption (VO2 max), or ventilatory threshold (VT), an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08) was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43) in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT) between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC evaluation in the assessment and interpretation of cardiorespiratory exercise testing. PMID:28638349

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Carolyn W., E-mail: carolyn.taylor@ctsu.ox.ac.uk; Wang, Zhe; Macaulay, Elizabeth

Purpose: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Methods and Materials: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this “mean heart dose.” Results: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28more » countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Conclusions: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.« less

Heart rate profile during exercise in patients with early repolarization.

PubMed

Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan

2010-09-01

Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P < 0.05). The lower heart rate increment (< 106 beats/min) and heart rate decrement (< 95 beats/min) were significantly associated with the presence of early repolarization. After adjustment for age and sex, the multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P < 0.001) for the lower heart rate increment and heart rate decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

The year 2012 in the European Heart Journal-Cardiovascular Imaging. Part II.

PubMed

Plein, Sven; Knuuti, Juhani; Edvardsen, Thor; Saraste, Antti; Piérard, Luc A; Maurer, Gerald; Lancellotti, Patrizio

2013-07-01

The part II of the best of the European Heart Journal - Cardiovascular Imaging in 2012 specifically focuses on studies of valvular heart diseases, heart failure, cardiomyopathies, and congenital heart diseases.

Association of heart rate profile during exercise with the severity of coronary artery disease.

PubMed

Cay, Serkan; Ozturk, Sezgin; Biyikoglu, Funda; Yildiz, Abdulkadir; Cimen, Tolga; Uygur, Belma; Tuna, Funda

2009-05-01

Coronary artery disease is the leading cause of morbidity and mortality around the world. Autonomic nervous system abnormalities are associated with coronary artery disease and its complications. Exercise stress tests are routinely used for the detection of the presence of coronary artery disease. In this study, we observed the association between heart rate profile during exercise and the severity of coronary artery disease. One hundred and sixty patients with abnormal exercise treadmill test (> or =1 mm horizontal or downsloping ST-segment depression; 119 men, 41 women; mean age = 57 +/- 9 years) were included in the study. Use of any drug affecting heart rate was not permitted. Resting heart rate before exercise, maximum heart rate during exercise, and resting heart rate after exercise (5 min later) were measured and two parameters were calculated: heart rate increment (maximum heart rate - resting heart rate before exercise) and heart rate decrement (maximum heart rate - resting heart rate after exercise). All patients underwent selective coronary angiography and subclassified into two groups according to stenotic lesion severity. Group 1 had at least 50% of stenotic lesion and group 2 had less than 50%. Patients in the first group had increased resting heart rate, decreased maximum heart rate, decreased heart rate increment, and decreased heart rate decrement compared with second group. All patients were classified into tertiles of resting heart rate, heart rate increment, and heart rate decrement level to evaluate whether these parameters were associated with severity of coronary artery stenosis in the study. The multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 21.888 (95% confidence interval 6.983-68.606) for the highest tertile of resting heart rate level compared with the lowest tertile. In addition, the multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 20.987 (95% confidence interval 6.635-66.387) for the lowest tertile of heart rate increment level compared with the highest tertile and 2.360 (95% confidence interval 1.004-5.544) for the lowest tertile of heart rate decrement level compared with the highest tertile. Altered autonomic nervous system regulation affects heart rate profile, increased resting heart rate, decreased heart rate increment, and decreased heart rate decrement, during exercise and this effect is strongly and independently associated with the severity of coronary artery disease.

Psychometric properties of HeartQoL, a core heart disease-specific health-related quality of life questionnaire, in Danish implantable cardioverter defibrillator recipients.

PubMed

Zangger, Graziella; Zwisler, Ann-Dorthe; Kikkenborg Berg, Selina; Kristensen, Marie S; Grønset, Charlotte N; Uddin, Jamal; Pedersen, Susanne S; Oldridge, Neil B; Thygesen, Lau C

2018-01-01

Background Patient-reported health-related quality of life is increasingly used as an outcome measure in clinical trials and as a performance measure to evaluate quality of care. The objective of this study was to assess the psychometric properties of the Danish HeartQoL questionnaire, a core heart disease-specific health-related quality of life questionnaire, in implantable cardioverter defibrillator recipients. Design This study involved cross-sectional and test-retest study designs. Method Implantable cardioverter defibrillator recipients in the cross-sectional study completed the HeartQoL, the Short-Form 36 Health Survey, and the Hospital Anxiety and Depression Scale. The HeartQoL structure, construct-related validity (convergent and discriminative) and reliability (internal consistency) were assessed. HeartQoL reproducibility (test-retest) was assessed in an independent sample of implantable cardioverter defibrillator recipients. Results Mokken scale analysis supported the bi-dimensional structure of HeartQoL among 358 implantable cardioverter defibrillator recipients. Convergent ( r > 0.72) and discriminative validity were confirmed. The HeartQoL scales demonstrated satisfactory internal consistency (Cronbach's alpha > 0.90). Test-retest reliability (two weeks interval) was assessed in 89 implantable cardioverter defibrillator recipients and found to be acceptable for each scale (intra-class correlation > 0.90). Conclusion The Danish HeartQoL questionnaire demonstrated satisfactory key psychometric attributes of validity and reliability in this implantable cardioverter defibrillator population. This study adds support for the HeartQoL as a core heart-specific health-related quality of life questionnaire in a broad group of patients with heart disease including implantable cardioverter defibrillator recipients.

Observational longitudinal cohort study to determine progression to heart failure in a screened community population: the Echocardiographic Heart of England Screening Extension (ECHOES-X) study

PubMed Central

Taylor, Clare J; Roalfe, Andrea K; Tait, Lynda; Davis, Russell C; Iles, Rachel; Derit, Marites; Hobbs, F D Richard

2014-01-01

Objectives Rescreen a large community cohort to examine the progression to heart failure over time and the role of natriuretic peptide testing in screening. Design Observational longitudinal cohort study. Setting 16 socioeconomically diverse practices in central England. Participants Participants from the original Echocardiographic Heart of England Screening (ECHOES) study were invited to attend for rescreening. Outcome measures Prevalence of heart failure at rescreening overall and for each original ECHOES subgroup. Test performance of N Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels at different thresholds for screening. Results 1618 of 3408 participants underwent screening which represented 47% of survivors and 26% of the original ECHOES cohort. A total of 176 (11%, 95% CI 9.4% to 12.5%) participants were classified as having heart failure at rescreening; 103 had heart failure with reduced ejection fraction (HFREF) and 73 had heart failure with preserved ejection fraction (HFPEF). Sixty-eight out of 1232 (5.5%, 95% CI 4.3% to 6.9%) participants who were recruited from the general population over the age of 45 and did not have heart failure in the original study, had heart failure on rescreening. An NT-proBNP cut-off of 400 pg/mL had sensitivity for a diagnosis of heart failure of 79.5% (95% CI 72.4% to 85.5%) and specificity of 87% (95% CI 85.1% to 88.8%). Conclusions Rescreening identified new cases of HFREF and HFPEF. Progression to heart failure poses a significant threat over time. The natriuretic peptide cut-off level for ruling out heart failure must be low enough to ensure cases are not missed at screening. PMID:25015472

Palliative and end-of-life care in stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

PubMed

Holloway, Robert G; Arnold, Robert M; Creutzfeldt, Claire J; Lewis, Eldrin F; Lutz, Barbara J; McCann, Robert M; Rabinstein, Alejandro A; Saposnik, Gustavo; Sheth, Kevin N; Zahuranec, Darin B; Zipfel, Gregory J; Zorowitz, Richard D

2014-06-01

The purpose of this statement is to delineate basic expectations regarding primary palliative care competencies and skills to be considered, learned, and practiced by providers and healthcare services across hospitals and community settings when caring for patients and families with stroke. Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were chosen to reflect the diversity and expertise of professional roles in delivering optimal palliative care. Writing group members were assigned topics relevant to their areas of expertise, reviewed the appropriate literature, and drafted manuscript content and recommendations in accordance with the American Heart Association's framework for defining classes and level of evidence and recommendations. The palliative care needs of patients with serious or life-threatening stroke and their families are enormous: complex decision making, aligning treatment with goals, and symptom control. Primary palliative care should be available to all patients with serious or life-threatening stroke and their families throughout the entire course of illness. To optimally deliver primary palliative care, stroke systems of care and provider teams should (1) promote and practice patient- and family-centered care; (2) effectively estimate prognosis; (3) develop appropriate goals of care; (4) be familiar with the evidence for common stroke decisions with end-of-life implications; (5) assess and effectively manage emerging stroke symptoms; (6) possess experience with palliative treatments at the end of life; (7) assist with care coordination, including referral to a palliative care specialist or hospice if necessary; (8) provide the patient and family the opportunity for personal growth and make bereavement resources available if death is anticipated; and (9) actively participate in continuous quality improvement and research. Addressing the palliative care needs of patients and families throughout the course of illness can complement existing practices and improve the quality of life of stroke patients, their families, and their care providers. There is an urgent need for further research in this area. © 2014 American Heart Association, Inc.

Both high and low HbA1c predict incident heart failure in type 2 diabetes mellitus.

PubMed

Parry, Helen M; Deshmukh, Harshal; Levin, Daniel; Van Zuydam, Natalie; Elder, Douglas H J; Morris, Andrew D; Struthers, Allan D; Palmer, Colin N A; Doney, Alex S F; Lang, Chim C

2015-03-01

Type 2 diabetes mellitus is an independent risk factor for heart failure development, but the relationship between incident heart failure and antecedent glycemia has not been evaluated. The Genetics of Diabetes Audit and Research in Tayside Study study holds data for 8683 individuals with type 2 diabetes mellitus. Dispensed prescribing, hospital admission data, and echocardiography reports were linked to extract incident heart failure cases from December 1998 to August 2011. All available HbA1c measures until heart failure development or end of study were used to model HbA1c time-dependently. Individuals were observed from study enrolment until heart failure development or end of study. Proportional hazard regression calculated heart failure development risk associated with specific HbA1c ranges accounting for comorbidities associated with heart failure, including blood pressure, body mass index, and coronary artery disease. Seven hundred and one individuals with type 2 diabetes mellitus (8%) developed heart failure during follow up (mean 5.5 years, ±2.8 years). Time-updated analysis with longitudinal HbA1c showed that both HbA1c <6% (hazard ratio =1.60; 95% confidence interval, 1.38-1.86; P value <0.0001) and HbA1c >10% (hazard ratio =1.80; 95% confidence interval, 1.60-2.16; P value <0.0001) were independently associated with the risk of heart failure. Both high and low HbA1c predicted heart failure development in our cohort, forming a U-shaped relationship. © 2015 American Heart Association, Inc.

Expectations outpace reality: physicians' use of care management tools for patients with chronic conditions.

PubMed

Carrier, Emily; Reschovsky, James

2009-12-01

Use of care management tools--such as group visits or patient registries--varies widely among primary care physicians whose practices care for patients with four common chronic conditions--asthma, diabetes, congestive heart failure and depression--according to a new national study by the Center for Studying Health System Change (HSC). For example, less than a third of these primary care physicians in 2008 reported their practices use nurse managers to coordinate care, and only four in 10 were in practices using registries to keep track of patients with chronic conditions. Physicians also used care management tools for patients with some chronic conditions but not others. Practice size and setting were strongly related to the likelihood that physicians used care management tools, with solo and smaller group practices least likely to use care management tools. The findings suggest that, along with experimenting with financial incentives for primary care physicians to adopt care management tools, policy makers might consider developing community-level care management resources, such as nurse managers, that could be shared among smaller physician practices.

History of the Congenital Heart Surgeons' Society.

PubMed

Mavroudis, Constantine; Williams, William G

2015-10-01

The Congenital Heart Surgeons' Society is a group of over 100 pediatric heart surgeons representing 72 institutions that specialize in the treatment of patients with congenital heart defects. The Society began in 1972 and incorporated as a not-for-profit charitable organization in 2004. It has become the face and voice of congenital heart surgery in North America. In 1985, the Society established a data center for multicenter clinical research studies to encourage congenital heart professionals to participate in improving outcomes for our patients. The goals of the Congenital Heart Surgeons' Society are to stimulate the study of congenital cardiac physiology, pathology, and management options which are instantiated in data collection, multi-institutional studies, and scientific meetings. Honest and open discussion of problems with possible solutions to the challenges facing congenital heart professionals have been the strength of the Congenital Heart Surgeons' Society. It is imperative for the growth of an organization to know from where it came in order to know to where it is going. The purpose of this article is to review the history of the Congenital Heart Surgeons' Society. © The Author(s) 2015.

A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana.

PubMed

Weinstein, A; Brickner, O; Lerman, H; Greemland, M; Bloch, M; Lester, H; Chisin, R; Sarne, Y; Mechoulam, R; Bar-Hamburger, R; Freedman, N; Even-Sapir, E

2008-06-01

Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.

Efficiently Maintaining a National Resource of Historical and Contemporary Biological Collections: The NHLBI Biorepository Model.

PubMed

Shea, Katheryn E; Wagner, Elizabeth L; Marchesani, Leah; Meagher, Kevin; Giffen, Carol

2017-02-01

Reducing costs by improving storage efficiency has been a focus of the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen Repository (Biorepository) and Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) programs for several years. Study specimen profiles were compiled using the BioLINCC collection catalog. Cost assessments and calculations on the return on investments to consolidate or reduce a collection, were developed and implemented. Over the course of 8 months, the NHLBI Biorepository evaluated 35 collections that consisted of 1.8 million biospecimens. A total of 23 collections were selected for consolidation, with a total of 1.2 million specimens located in 21,355 storage boxes. The consolidation resulted in a savings of 4055 boxes of various sizes and 10.2 mechanical freezers (∼275 cubic feet) worth of space. As storage costs in a biorepository increase over time, the development and use of information technology tools to assess the potential advantage and feasiblity of vial consolidation can reduce maintenance expenses.

Effect of a Community-Based Nursing Intervention on Mortality in Chronically Ill Older Adults: A Randomized Controlled Trial

PubMed Central

Coburn, Kenneth D.; Marcantonio, Sherry; Lazansky, Robert; Keller, Maryellen; Davis, Nancy

2012-01-01

Background Improving the health of chronically ill older adults is a major challenge facing modern health care systems. A community-based nursing intervention developed by Health Quality Partners (HQP) was one of 15 different models of care coordination tested in randomized controlled trials within the Medicare Coordinated Care Demonstration (MCCD), a national US study. Evaluation of the HQP program began in 2002. The study reported here was designed to evaluate the survival impact of the HQP program versus usual care up to five years post-enrollment. Methods and Findings HQP enrolled 1,736 adults aged 65 and over, with one or more eligible chronic conditions (coronary artery disease, heart failure, diabetes, asthma, hypertension, or hyperlipidemia) during the first six years of the study. The intervention group (n = 873) was offered a comprehensive, integrated, and tightly managed system of care coordination, disease management, and preventive services provided by community-based nurse care managers working collaboratively with primary care providers. The control group (n = 863) received usual care. Overall, a 25% lower relative risk of death (hazard ratio [HR] 0.75 [95% CI 0.57–1.00], p = 0.047) was observed among intervention participants with 86 (9.9%) deaths in the intervention group and 111 (12.9%) deaths in the control group during a mean follow-up of 4.2 years. When covariates for sex, age group, primary diagnosis, perceived health, number of medications taken, hospital stays in the past 6 months, and tobacco use were included, the adjusted HR was 0.73 (95% CI 0.55–0.98, p = 0.033). Subgroup analyses did not demonstrate statistically significant interaction effects for any subgroup. No suspected program-related adverse events were identified. Conclusions The HQP model of community-based nurse care management appeared to reduce all-cause mortality in chronically ill older adults. Limitations of the study are that few low-income and non-white individuals were enrolled and implementation was in a single geographic region of the US. Additional research to confirm these findings and determine the model's scalability and generalizability is warranted. Trial Registration ClinicalTrials.gov NCT01071967 Please see later in the article for the Editors' Summary PMID:22815653

[Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?].

PubMed

Bounhoure, Jean-Paul; Galinier, Michel; Roncalli, Jerôme; Massabuau, Pierre

2014-01-01

Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure.

Neurocardiology: Structure-Based Function.

PubMed

Ardell, Jeffrey L; Armour, John Andrew

2016-09-15

Cardiac control is mediated via a series of reflex control networks involving somata in the (i) intrinsic cardiac ganglia (heart), (ii) intrathoracic extracardiac ganglia (stellate, middle cervical), (iii) superior cervical ganglia, (iv) spinal cord, (v) brainstem, and (vi) higher centers. Each of these processing centers contains afferent, efferent, and local circuit neurons, which interact locally and in an interdependent fashion with the other levels to coordinate regional cardiac electrical and mechanical indices on a beat-to-beat basis. This control system is optimized to respond to normal physiological stressors (standing, exercise, and temperature); however, it can be catastrophically disrupted by pathological events such as myocardial ischemia. In fact, it is now recognized that autonomic dysregulation is central to the evolution of heart failure and arrhythmias. Autonomic regulation therapy is an emerging modality in the management of acute and chronic cardiac pathologies. Neuromodulation-based approaches that target select nexus points of this hierarchy for cardiac control offer unique opportunities to positively affect therapeutic outcomes via improved efficacy of cardiovascular reflex control. As such, understanding the anatomical and physiological basis for such control is necessary to implement effectively novel neuromodulation therapies. © 2016 American Physiological Society. Compr Physiol 6:1635-1653, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.

PubMed

Thompson, Brian R; Metzger, Joseph M

2014-09-01

The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. © 2014 Wiley Periodicals, Inc.

On the Evolution of the Cardiac Pacemaker

PubMed Central

Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

2017-01-01

The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

Biocompatibility of Hydrogen-Diluted Amorphous Silicon Carbide Thin Films for Artificial Heart Valve Coating

NASA Astrophysics Data System (ADS)

Rizal, Umesh; Swain, Bhabani S.; Rameshbabu, N.; Swain, Bibhu P.

2018-01-01

Amorphous silicon carbide (a-SiC:H) thin films were synthesized using trichloromethylsilane by a hot wire chemical vapor deposition process. The deposited films were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, x-ray diffraction and x-ray photoelectron spectroscopy to confirm its chemical bonding, structural network and composition of the a-SiC:H films. The optical microscopy images reveal that hydrogen dilution increased the surface roughness and pore density of a-SiC:H thin film. The Raman spectroscopy and FTIR spectra reveal chemical network consisting of Si-Si, C-C and Si-C bonds, respectively. The XRD spectroscopy and Raman spectroscopy indicate a-SiC:H still has short-range order. In addition, in vitro cytotoxicity test ensures the behavior of cell-semiconductor hybrid to monitor the proper coordination. The live-dead assays and MTT assay reveal an increase in green nucleus cell, and cell viability is greater than 88%, respectively, showing non-toxic nature of prepared a-SiC:H film. Moreover, the result indicated by direct contact assay, and cell prefers to adhere and proliferate on a-SiC:H thin films having a positive effect as artificial heart valve coating material.

Process of Transition for Congenital Heart Patients: Preventing Loss to Follow-up.

PubMed

Habibi, Hajar; Emmanuel, Yaso; Chung, Natali

The aim of this article is to provide an overview of our nurse-led transition clinic provided to congenital heart disease patients moving from pediatric into adult care setting. Nurse-led transition clinic was analyzed at various stages of young adult care from an early stage of 12 to 14 years to entering adult setting at 16 years or older. Overview of current transition service for young adults being transferred from pediatric into adult services highlights the integral role of clinical nurse specialist as a coordinator of care. The result of the service overview indicates that nurse-led transition service enables patients to build on their knowledge. This is achieved by providing them time and the opportunities to develop an understanding of their condition and the attitudes required to engage with the adult care setting as indicated in the psychology questionnaire from transition day. A nurse-led transition clinic enhances long-term care of patients by supporting the young adults and their family/carer through the transition and transfer of the care to promote the young adult's understanding of their condition and to prevent any lost to follow-up.

Case conferences between general practitioners and specialist teams to plan end of life care of people with end stage heart failure and lung disease: an exploratory pilot study

PubMed Central

2014-01-01

Background Most people die of non-malignant disease, but most patients of specialist palliative care services have cancer. Adequate end of life care for people with non-malignant disease requires acknowledgement of their limited prognosis and appropriate care planning. Case conferences between specialist palliative care services and GPs improve outcomes in cancer-based populations. We report a pilot study of case conferences between the patient’s GP and specialist staff to facilitate care planning for people with end stage heart failure or non-malignant lung disease in a regional health service in Queensland Australia. Methods Single face to face case conferences about patients with a primary diagnosis of advanced heart failure or respiratory failure from non-malignant disease were conducted between a palliative care consultant, a case management nurse and the patient’s GP. Annualised rates of service utilisation (emergency department [ED] presentations, ED discharges back to home, hospital admissions, and admission length of stay) before and after case conference were calculated. Content and counts of case conference recommendations, and the rate of adherence to recommendations were also assessed. A process evaluation of case conferences was undertaken. Results Twenty-three case conferences involving 21 GPs were conducted between November 2011 and November 2012. One GP refused to participate. Ten patients died, three at home. Of 82 management recommendations made, 55 (67%) were enacted. ED admissions fell from 13.9 per annum (pa) to 2.1 (difference 11.8, 95% CI 2.2-21.3, p = 0.001); ED admissions leading to discharge home from 3.9 to 0.4 pa (difference 3.5, 95% CI -0.4-7.5, p = 0.05); hospital admissions from 11.4 to 3.5 pa (difference 7.9, 95% CI 2.2-13.7, p = 0.002); and length of stay from 7.0 to 3.7 days (difference 3.4, 95% CI 0.9-5.8, p = 0.007). Participating health professionals were enthusiastic about the process. Conclusions This pilot is the initial step in the development and testing of a complex intervention based on a model of integrated care. A single case conference involving the patient’s heart or lung failure team is associated with significant reductions in service utilization, apparently by improving case coordination, enhancing symptom management and assessing and managing carer needs. A randomized controlled trial is being developed. Trial registration Australian and New Zealand Controlled Trials Register ACTRN12613001377729: Registered 16/12/2013. PMID:24829539

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147

Expression and activity of the 5'-adenosine monophosphate-activated protein kinase pathway in selected tissues during chicken embryonic development.

PubMed

Proszkowiec-Weglarz, M; Richards, M P

2009-01-01

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved serine-threonine protein kinase and a key part of a kinase-signaling cascade that senses cellular energy status (adenosine monophosphate:adenosine triphosphate ratio) and acts to maintain energy homeostasis by coordinately regulating energy-consuming and energy-generating metabolic pathways. The objective of this study was to investigate aspects of the AMPK pathway in the liver, brain, breast muscle, and heart from d 12 of incubation through hatch in chickens. We first determined mRNA and protein expression profiles for a major upstream AMPK kinase, LKB1, which is known to activate (phosphorylate) AMPK in response to increases in the adenosine monophosphate:adenosine triphosphate ratio. Expression of LKB1 protein was greatest in the brain, which demonstrated tissue-specific patterns for phosphorylation. Next, AMPK subunit mRNA and protein expression profiles were determined. Significant changes in AMPK subunit mRNA expression occurred in all tissues from d 12 of incubation to hatch. Differences in the levels of active (phosphorylated) AMPK as well as alpha and beta subunit proteins were observed in all 4 tissues during embryonic development. Finally, we determined the protein level and phosphorylation status of an important downstream target for AMPK, acetyl-coenzyme A carboxylase. The expression of acetyl-co-enzyme A carboxylase and phosphorylated acetyl-coenzyme A was greater in the brain than the liver, but was undetectable by Western blotting in the breast muscle and heart throughout the period of study. Together, our results are the first to demonstrate the expression and activity of the AMPK pathway in key tissues during the transition from embryonic to posthatch development in chickens.

Structured review: evaluating the effectiveness of nurse case managers in improving health outcomes in three major chronic diseases.

PubMed

Sutherland, Debbie; Hayter, Mark

2009-11-01

This paper presents the findings of a review and appraisal of the evidence for the effectiveness of nurse case management in improving health outcomes for patients living either with Diabetes, Chronic Obstructive Pulmonary Disease or Coronary Heart Disease. Long term chronic health conditions provide some of the greatest challenges to western health care systems. In the UK, three of the most significant chronic conditions are Diabetes, Chronic Obstructive Pulmonary Disease and Coronary Heart Disease. Patients with these long term conditions are high users of health services who often receive unplanned, poorly co-ordinated, ad-hoc care in response to an exacerbation or crisis. To counter this, the nurse case manager is identified as a central aspect of improving care for these patients. However, the evidence for the effectiveness of nurse case management in improving health outcomes for the chronically ill is scarce. A structured review of the literature. The review was undertaken focussing on studies that evaluated nurse case management with one or all of the three major long term chronic conditions. A total of 108 papers were initially reviewed and filtered to leave 75 citations that were appraised. About 18 papers were finally included in the review and subject to thematic analysis based on the health outcomes evaluated in the studies. Significantly positive results were reported for nurse case management impact on five health outcomes; 'objective clinical measurements', 'quality of life and functionality', 'patient satisfaction', 'adherence to treatment' and 'self care and service use'. The evidence generated in this review suggests that nurse case managers have the potential to achieve improved health outcomes for patients with long term conditions. Further research is required to support role development and create a more targeted approach to the intervention.

The effects of bilateral stimulation of the subthalamic nucleus on heart rate variability in patients with Parkinson's disease.

PubMed

Liu, Kang-Du; Shan, Din-E; Kuo, Terry B J; Yang, Cheryl C H

2013-07-01

The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation "on" and second night "off"). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation "on" groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (ρ = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.

High-Intensity Interval Training in Heart Transplant Recipients: A Systematic Review with Meta-Analysis.

PubMed

Perrier-Melo, Raphael José; Figueira, Fernando Augusto Marinho Dos Santos; Guimarães, Guilherme Veiga; Costa, Manoel da Cunha

2018-02-01

Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart transplantation'' OR "cardiac transplantation". The words used in combination (AND) were: "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.

PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

PubMed

Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

2010-11-01

A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ might confer to this novel compound an important role for the development of new (99m)Tc and (188)Re-nitrido radiopharmaceuticals. Copyright © 2010 Elsevier Inc. All rights reserved.

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in aged mice.

PubMed

Rakov, Helena; Engels, Kathrin; Hönes, Georg Sebastian; Brix, Klaudia; Köhrle, Josef; Moeller, Lars Christian; Zwanziger, Denise; Führer, Dagmar

2017-12-22

Sex and age play a role in the prevalence of thyroid dysfunction (TD), but their interrelationship for manifestation of hyper- and hypothyroidism is still not well understood. Using a murine model, we asked whether sex impacts the phenotypes of hyper- and hypothyroidism at two life stages. Hyper- and hypothyroidism were induced by i.p. T4 or MMI/ClO 4 -/LoI treatment over 7 weeks in 12- and 20-months-old female and male C57BL/6N mice. Control animals underwent PBS treatment (n = 7-11 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination and strength) and serum thyroid hormone (TH) status. Distinct sex impact was found in eu- and hyperthyroid mice, while phenotypic traits of hypothyroidism were similar in male and female mice. No sex difference was found in TH status of euthyroid mice; however, T4 treatment resulted in twofold higher TT4, FT4 and FT3 serum concentrations in adult and old females compared to male animals. Hyperthyroid females consistently showed higher locomotor activity and better coordination but more impairment of muscle function by TH excess at adult age. Importantly and in contrast to male mice, adult and old hyperthyroid female mice showed increased body weight. Higher body temperature in female mice was confirmed in all age groups. No sex impact was found on heart rate irrespective of TH status in adult and old mice. By comparison of male and female mice with TD at two life stages, we found that sex modulates TH action in an organ- and function-specific manner. Sex differences were more pronounced under hyperthyroid conditions. Importantly, sex-specific differences in features of TD in adult and old mice were not conclusively explained by serum TH status in mice.

[Congenital heart disease mortality in Spain during a 10 year period (2003-2012)].

PubMed

Pérez-Lescure Picarzo, Javier; Mosquera González, Margarita; Latasa Zamalloa, Pello; Crespo Marcos, David

2018-05-01

Congenital heart disease is a major cause of infant mortality in developed countries. In Spain, there are no publications at national level on mortality due to congenital heart disease. The aim of this study is to analyse mortality in infants with congenital heart disease, lethality of different types of congenital heart disease, and their variation over a ten-year period. A retrospective observational study was performed to evaluate mortality rate of children under one year old with congenital heart disease, using the minimum basic data set, from 2003 to 2012. Mortality rate and relative risk of mortality were estimated by Poisson regression. There were 2,970 (4.58%) infant deaths in a population of 64,831 patients with congenital heart disease, with 73.8% of deaths occurring during first week of life. Infant mortality rate in patients with congenital heart disease was 6.23 per 10,000 live births, and remained constant during the ten-year period of the study, representing 18% of total infant mortality rate in Spain. The congenital heart diseases with highest mortality rates were hypoplastic left heart syndrome (41.4%), interruption of aortic arch (20%), and total anomalous pulmonary drainage (16.8%). Atrial septal defect (1%) and pulmonary stenosis (1.1%) showed the lowest mortality rate. Congenital heart disease was a major cause of infant mortality with no variations during the study period. The proportion of infants who died in our study was similar to other similar countries. In spite of current medical advances, some forms of congenital heart disease show very high mortality rates. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Heart failure symptom relationships: a systematic review.

PubMed

Herr, Janet K; Salyer, Jeanne; Lyon, Debra E; Goodloe, Lauren; Schubert, Christine; Clement, Dolores G

2014-01-01

Heart failure is a prevalent chronic health condition in the United States. Individuals who have heart failure experience as many as 2 to 9 symptoms. The examination of relationships among heart failure symptoms may benefit patients and clinicians who are charged with managing heart failure symptoms. The purpose of this systematic review was to summarize what is known about relationships among heart failure symptoms, a precursor to the identification of heart failure symptom clusters, as well as to examine studies specifically addressing symptom clusters described in this population. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in the conduct of this systematic review. PubMed, PsychINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Database were searched using the search term heart failure in combination with a pair of symptoms. Of a total of 1316 studies identified from database searches, 34 were included in this systematic review. More than 1 investigator found a moderate level of correlation between depression and fatigue, depression and anxiety, depression and sleep, depression and pain, anxiety and fatigue, and dyspnea and fatigue. The findings of this systematic review provide support for the presence of heart failure symptom clusters. Depression was related to several of the symptoms, providing an indication to clinicians that individuals with heart failure who experience depression may have other concurrent symptoms. Some symptom relationships such as the relationships between fatigue and anxiety or sleep or pain were dependent on the symptom characteristics studied. Symptom prevalence in the sample and restricted sampling may influence the robustness of the symptom relationships. These findings suggest that studies defining the phenotype of individual heart failure symptoms may be a beneficial step in the study of heart failure symptom clusters.

Sex differences in time from self-reported heart trouble to heart disease death in the Alameda County Study. Significance of time dependence of risk variable effects.

PubMed

Cohn, B A; Wingard, D L; Cohen, R D; Cirillo, P M; Kaplan, G A

1990-03-01

In a previous analysis from the Alameda County Study, it was observed that although men had higher heart disease mortality rates than women, there was no male excess in the prevalence of self-reported heart disease morbidity at baseline or in new reports of morbidity 9 years past baseline. This apparent contradiction might occur because women report less severe heart disease than men. In the present study, this hypothesis was evaluated by examining whether self-reported heart trouble was more strongly associated with subsequent heart disease mortality for men than for women in a representative sample of the population of Alameda County, California, selected in 1965 and followed for mortality for 19 years (n = 3,742). In a time-dependent Cox model, self-reported heart trouble was a stronger predictor of heart disease mortality for men, but only during the early years of follow-up (p = 0.00). This effect was due to a shorter time to death for men who reported heart trouble. The relative hazard for men reporting heart trouble was 6.6 (95% confidence interval (CI) 3.7-11.6) at baseline, declining to 3.2 (95% CI 2.2-4.5) by 5 years past baseline and 1.5 (95% CI 0.9-2.5) by 10 years past baseline. Self-reported heart trouble was a consistent predictor of subsequent heart disease mortality for women over the 19-year follow-up period (relative hazard = 2.0, 95% CI 1.4-2.8). Sex differences in the prognosis of self-reported heart trouble were masked in non-time-dependent analyses. These results illustrate that consideration of time dependence may be required for meaningful analysis of long-term cohort studies. Possible explanations of the shorter time to death for men who reported heart trouble are discussed.

Heart Rate Dynamics During A Treadmill Cardiopulmonary Exercise Test in Optimized Beta-Blocked Heart Failure Patients

PubMed Central

Carvalho, Vitor Oliveira; Guimarães, Guilherme Veiga; Ciolac, Emmanuel Gomes; Bocchi, Edimar Alcides

2008-01-01

BACKGROUND Calculating the maximum heart rate for age is one method to characterize the maximum effort of an individual. Although this method is commonly used, little is known about heart rate dynamics in optimized beta-blocked heart failure patients. AIM The aim of this study was to evaluate heart rate dynamics (basal, peak and % heart rate increase) in optimized beta-blocked heart failure patients compared to sedentary, normal individuals (controls) during a treadmill cardiopulmonary exercise test. METHODS Twenty-five heart failure patients (49±11 years, 76% male), with an average LVEF of 30±7%, and fourteen controls were included in the study. Patients with atrial fibrillation, a pacemaker or noncardiovascular functional limitations or whose drug therapy was not optimized were excluded. Optimization was considered to be 50 mg/day or more of carvedilol, with a basal heart rate between 50 to 60 bpm that was maintained for 3 months. RESULTS Basal heart rate was lower in heart failure patients (57±3 bpm) compared to controls (89±14 bpm; p<0.0001). Similarly, the peak heart rate (% maximum predicted for age) was lower in HF patients (65.4±11.1%) compared to controls (98.6±2.2; p<0.0001). Maximum respiratory exchange ratio did not differ between the groups (1.2±0.5 for controls and 1.15±1 for heart failure patients; p=0.42). All controls reached the maximum heart rate for their age, while no patients in the heart failure group reached the maximum. Moreover, the % increase of heart rate from rest to peak exercise between heart failure (48±9%) and control (53±8%) was not different (p=0.157). CONCLUSION No patient in the heart failure group reached the maximum heart rate for their age during a treadmill cardiopulmonary exercise test, despite the fact that the percentage increase of heart rate was similar to sedentary normal subjects. A heart rate increase in optimized beta-blocked heart failure patients during cardiopulmonary exercise test over 65% of the maximum age-adjusted value should be considered an effort near the maximum. This information may be useful in rehabilitation programs and ischemic tests, although further studies are required. PMID:18719758

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

PubMed Central

Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

2016-01-01

Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans.

PubMed

Lile, Joshua A; Stoops, William W; Rush, Craig R; Negus, S Stevens; Glaser, Paul E A; Hatton, Kevin W; Hays, Lon R

2016-08-01

A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30mg/70kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. These coordinated studies successfully established drug versus non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association.

PubMed

Becker, Lance B; Aufderheide, Tom P; Geocadin, Romergryko G; Callaway, Clifton W; Lazar, Ronald M; Donnino, Michael W; Nadkarni, Vinay M; Abella, Benjamin S; Adrie, Christophe; Berg, Robert A; Merchant, Raina M; O'Connor, Robert E; Meltzer, David O; Holm, Margo B; Longstreth, William T; Halperin, Henry R

2011-11-08

The guidelines presented in this consensus statement are intended to serve researchers, clinicians, reviewers, and regulators in the selection of the most appropriate primary outcome for a clinical trial of cardiac arrest therapies. The American Heart Association guidelines for the treatment of cardiac arrest depend on high-quality clinical trials, which depend on the selection of a meaningful primary outcome. Because this selection process has been the subject of much controversy, a consensus conference was convened with national and international experts, the National Institutes of Health, and the US Food and Drug Administration. The Research Working Group of the American Heart Association Emergency Cardiovascular Care Committee nominated subject leaders, conference attendees, and writing group members on the basis of their expertise in clinical trials and a diverse perspective of cardiovascular and neurological outcomes (see the online-only Data Supplement). Approval was obtained from the Emergency Cardiovascular Care Committee and the American Heart Association Manuscript Oversight Committee. Preconference position papers were circulated for review; the conference was held; and postconference consensus documents were circulated for review and comments were invited from experts, conference attendees, and writing group members. Discussions focused on (1) when after cardiac arrest the measurement time point should occur; (2) what cardiovascular, neurological, and other physiology should be assessed; and (3) the costs associated with various end points. The final document underwent extensive revision and peer review by the Emergency Cardiovascular Care Committee, the American Heart Association Science Advisory and Coordinating Committee, and oversight committees. There was consensus that no single primary outcome is appropriate for all studies of cardiac arrest. The best outcome measure is the pairing of a time point and physiological condition that will best answer the question under study. Conference participants were asked to assign an outcome to each of 4 hypothetical cases; however, there was not complete agreement on an ideal outcome measure even after extensive discussion and debate. There was general consensus that it is appropriate for earlier studies to enroll fewer patients and to use earlier time points such as return of spontaneous circulation, simple "alive versus dead," hospital mortality, or a hemodynamic parameter. For larger studies, a longer time point after arrest should be considered because neurological assessments fluctuate for at least 90 days after arrest. For large trials designed to have a major impact on public health policy, longer-term end points such as 90 days coupled with neurocognitive and quality-of-life assessments should be considered, as should the additional costs of this approach. For studies that will require regulatory oversight, early discussions with regulatory agencies are strongly advised. For neurological assessment of post-cardiac arrest patients, researchers may wish to use the Cerebral Performance Categories or modified Rankin Scale for global outcomes. Although there is no single recommended outcome measure for trials of cardiac arrest care, the simple Cerebral Performance Categories or modified Rankin Scale after 90 days provides a reasonable outcome parameter for many trials. The lack of an easy-to-administer neurological functional outcome measure that is well validated in post-cardiac arrest patients is a major limitation to the field and should be a high priority for future development.

Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

PubMed

Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

2012-01-01

Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

Discovery of novel heart rate-associated loci using the Exome Chip

PubMed Central

van den Berg, Marten E.; Warren, Helen R.; Cabrera, Claudia P.; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A.; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J.; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A.; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V.; Lyytikäinen, Leo-Pekka; Hall, Leanne M.; van Setten, Jessica; Trompet, Stella; Prins, Bram P.; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A.; Silva, Claudia T.; Alonso, Alvaro; Bis, Joshua C.; de Boer, Rudolf; de Haan, Hugoline G.; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F.; Doney, Alex S. F.; Ellinor, Patrick T.; Eppinga, Ruben N.; Felix, Stephan B.; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B.; Heckbert, Susan R.; Huang, Paul L.; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K.; Kolcic, Ivana; Launer, Lenore J.; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W.; Mangino, Massimo; Morris, Andrew D.; Mulas, Antonella; Murray, Alison D.; Nelson, Christopher P.; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J.; Poulter, Neil; Psaty, Bruce M.; Qi, Lihong; Raitakari, Olli T.; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F.; Soliman, Elsayed Z.; Spector, Timothy D.; Stanton, Alice V.; Stirrups, Kathleen E.; Taylor, Kent D.; Tobin, Martin D.; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W.; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M.; Zeggini, Eleftheria; Jukema, J. Wouter; Asselbergs, Folkert W.; Samani, Nilesh J.; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A.; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J.; Palmer, Colin N. A.; Sanna, Serena; Mook-Kanamori, Dennis O.; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I.; Dörr, Marcus; O'Donnell, Chris J.; Hayward, Caroline; Arking, Dan E.; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H.; Munroe, Patricia B.

2017-01-01

Abstract Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. PMID:28379579

Discovery of novel heart rate-associated loci using the Exome Chip.

PubMed

van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V; Lyytikäinen, Leo-Pekka; Hall, Leanne M; van Setten, Jessica; Trompet, Stella; Prins, Bram P; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A; Silva, Claudia T; Alonso, Alvaro; Bis, Joshua C; de Boer, Rudolf; de Haan, Hugoline G; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F; Doney, Alex S F; Ellinor, Patrick T; Eppinga, Ruben N; Felix, Stephan B; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Huang, Paul L; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K; Kolcic, Ivana; Launer, Lenore J; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W; Mangino, Massimo; Morris, Andrew D; Mulas, Antonella; Murray, Alison D; Nelson, Christopher P; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J; Poulter, Neil; Psaty, Bruce M; Qi, Lihong; Raitakari, Olli T; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F; Soliman, Elsayed Z; Spector, Timothy D; Stanton, Alice V; Stirrups, Kathleen E; Taylor, Kent D; Tobin, Martin D; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M; Zeggini, Eleftheria; Jukema, J Wouter; Asselbergs, Folkert W; Samani, Nilesh J; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J; Palmer, Colin N A; Sanna, Serena; Mook-Kanamori, Dennis O; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I; Dörr, Marcus; O'Donnell, Chris J; Hayward, Caroline; Arking, Dan E; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H; Munroe, Patricia B

2017-06-15

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. © The Author 2017. Published by Oxford University Press.

In Vivo Measurements in Mice in the Bion-M 1 Mission

NASA Astrophysics Data System (ADS)

Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to microgravity do not depend on the size of the organism.

An Acuity Tool for Heart Failure Case Management: Quantifying Workload, Service Utilization, and Disease Severity.

PubMed

Kilgore, Matthew D

The cardiology service line director at a health maintenance organization (HMO) in Washington State required a valid, reliable, and practical means for measuring workloads and other productivity factors for six heart failure (HF) registered nurse case managers located across three geographical regions. The Kilgore Heart Failure Case Management (KHFCM) Acuity Tool was systematically designed, developed, and validated to measure workload as a dependent function of the number of heart failure case management (HFCM) services rendered and the duration of times spent on various care duties. Research and development occurred at various HMO-affiliated internal medicine and cardiology offices throughout Western Washington. The concepts, methods, and principles used to develop the KHFCM Acuity Tool are applicable for any type of health care professional aiming to quantify workload using a high-quality objective tool. The content matter, scaling, and language on the KHFCM Acuity Tool are specific to HFCM settings. The content matter and numeric scales for the KHFCM Acuity Tool were developed and validated using a mixed-method participant action research method applied to a group of six outpatient HF case managers and their respective caseloads. The participant action research method was selected, because the application of this method requires research participants to become directly involved in the diagnosis of research problems, the planning and execution of actions taken to address those problems, and the implementation of progressive strategies throughout the course of the study, as necessary, to produce the most credible and practical practice improvements (; ; ; ). Heart failure case managers served clients with New York Heart Association Functional Class III-IV HF (), and encounters were conducted primarily by telephone or in-office consultation. A mix of qualitative and quantitative results demonstrated a variety of quality improvement outcomes achieved by the design and practice application of the KHFCM Acuity Tool. Quality improvement outcomes included a more valid reflection of encounter times and demonstration of the KHFCM Acuity Tool as a reliable, practical, credible, and satisfying tool for reflecting HF case manager workloads and HF disease severity. The KHFCM Acuity Tool defines workload simply as a function of the number of HFCM services performed and the duration of time spent on a client encounter. The design of the tool facilitates the measure of workload, service utilization, and HF disease characteristics, independently from the overall measure of acuity, so that differences in individual case manager practice, as well as client characteristics within sites, across sites, and potentially throughout annual seasons, can be demonstrated. Data produced from long-term applications of the KHFCM Acuity Tool, across all regions, could serve as a driver for establishing systemwide HFCM productivity benchmarks or standards of practice for HF case managers. Data produced from localized applications could serve as a reference for coordinating staffing resources or developing HFCM productivity benchmarks within individual regions or sites.

Lifestyle modification with diet and exercise in obese patients with heart failure - A pilot study

USDA-ARS?s Scientific Manuscript database

There is a paucity of data regarding intentional weight loss in obese heart failure patients. This study sought to ascertain the safety and effectiveness of a lifestyle modification program in patients with systolic heart failure and metabolic syndrome. Patients (n=20) with systolic heart failure (e...

Detrimental effects of acute hyperglycaemia on the rat heart.

PubMed

Mapanga, R F; Joseph, D; Symington, B; Garson, K-L; Kimar, C; Kelly-Laubscher, R; Essop, M Faadiel

2014-03-01

Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways (NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection. We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Australia's health care reform agenda: implications for the nurses' role in chronic heart failure management.

PubMed

Betihavas, Vasiliki; Newton, Phillip J; Du, Hui Yun; Macdonald, Peter S; Frost, Steven A; Stewart, Simon; Davidson, Patricia M

2011-08-01

The importance of the nursing role in chronic heart failure (CHF) management is increasingly recognised. With the recent release of the National Health and Hospitals Reform Commission (NHHRC) report in Australia, a review of nursing roles in CHF management is timely and appropriate. This paper aims to discuss the implications of the NHHRC report and nursing roles in the context of CHF management in Australia. The electronic databases, Thomson Rheuters Web of Knowledge, Scopus and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), were searched using keywords including; "heart failure", "management", "Australia" and "nursing". In addition policy documents were reviewed including statements and reports from key professional organisations and Government Departments to identify issues impacting on nursing roles in CHF management. There is a growing need for the prevention and control of chronic conditions, such as CHF. This involves an increasing emphasis on specialist cardiovascular nurses in community based settings, both in outreach and inreach health service models. This review has highlighted the need to base nursing roles on evidence based principles and identify the importance of the nursing role in coordinating and managing CHF care in both independent and collaborative practice settings. The importance of the nursing role in early chronic disease symptom recognition and implementing strategies to prevent further deterioration of individuals is crucial to improving health outcomes. Consideration should be given to ensure that evidence based principles are adopted in models of nursing care. Copyright © 2010 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Relationship between mathematical abstraction in learning parallel coordinates concept and performance in learning analytic geometry of pre-service mathematics teachers: an investigation

NASA Astrophysics Data System (ADS)

Nurhasanah, F.; Kusumah, Y. S.; Sabandar, J.; Suryadi, D.

2018-05-01

As one of the non-conventional mathematics concepts, Parallel Coordinates is potential to be learned by pre-service mathematics teachers in order to give them experiences in constructing richer schemes and doing abstraction process. Unfortunately, the study related to this issue is still limited. This study wants to answer a research question “to what extent the abstraction process of pre-service mathematics teachers in learning concept of Parallel Coordinates could indicate their performance in learning Analytic Geometry”. This is a case study that part of a larger study in examining mathematical abstraction of pre-service mathematics teachers in learning non-conventional mathematics concept. Descriptive statistics method is used in this study to analyze the scores from three different tests: Cartesian Coordinate, Parallel Coordinates, and Analytic Geometry. The participants in this study consist of 45 pre-service mathematics teachers. The result shows that there is a linear association between the score on Cartesian Coordinate and Parallel Coordinates. There also found that the higher levels of the abstraction process in learning Parallel Coordinates are linearly associated with higher student achievement in Analytic Geometry. The result of this study shows that the concept of Parallel Coordinates has a significant role for pre-service mathematics teachers in learning Analytic Geometry.

Heart murmur detection based on wavelet transformation and a synergy between artificial neural network and modified neighbor annealing methods.

PubMed

Eslamizadeh, Gholamhossein; Barati, Ramin

2017-05-01

Early recognition of heart disease plays a vital role in saving lives. Heart murmurs are one of the common heart problems. In this study, Artificial Neural Network (ANN) is trained with Modified Neighbor Annealing (MNA) to classify heart cycles into normal and murmur classes. Heart cycles are separated from heart sounds using wavelet transformer. The network inputs are features extracted from individual heart cycles, and two classification outputs. Classification accuracy of the proposed model is compared with five multilayer perceptron trained with Levenberg-Marquardt, Extreme-learning-machine, back-propagation, simulated-annealing, and neighbor-annealing algorithms. It is also compared with a Self-Organizing Map (SOM) ANN. The proposed model is trained and tested using real heart sounds available in the Pascal database to show the applicability of the proposed scheme. Also, a device to record real heart sounds has been developed and used for comparison purposes too. Based on the results of this study, MNA can be used to produce considerable results as a heart cycle classifier. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploratory study into the awareness of heart diseases among Emirati women (UAE) and their health seeking behaviour- a qualitative study.

PubMed

Khan, Sarah; Khoory, Ayesha; Al Zaffin, Dhabia; Al Suwaidi, Meera

2016-11-07

Cardiovascular diseases were the leading cause of death in women in the United Arab Emirates (UAE) in 2010. The UAE is expected to experience a tripling of heart diseases in the next two decades as risk factors for heart diseases increase. Research shows that first year survival rates of younger women suffering from a heart attack are lower than in men. Women present with a wider range of symptoms for heart diseases than men; non-recognition of atypical symptoms may explain the delay in seeking treatment and poor prognosis following heart diseases in women. No known study on awareness of heart diseases among women has been carried out in the Middle Eastern region. Social constructionist and interpretivist epistemological approaches have been considered in this qualitative study to explore the awareness of heart diseases and the health seeking behavior of Emirati women. Convenience sampling was used to recruit 41 Emirati women. Three focus groups and six in-depth semi-structured interviews were conducted to obtain data. Thematic content analysis was applied to the data following transcription and translation of recordings. Emirati women had limited knowledge on heart diseases. Women were generally unaware of the atypical symptoms, commonly experienced by women however they identified most risk factors associated with heart diseases. Lack of awareness of disease severity and symptoms, sociocultural influences and distrust in the healthcare system were considered the main barriers to seeking prompt treatment. This study clearly identified gaps and inaccuracies in knowledge of heart diseases, which could contribute to delayed health seeking action and possibly poorer prognosis among Emirati women. Absence of initiatives to educate women on cardiovascular diseases in UAE has erroneously deemed it a less serious concern among Emirati women. The findings from this study provide clear indications of the need to increase accountability of the healthcare system and to develop culturally relevant, gender specific, age focused, heart diseases related public health awareness campaigns in UAE.

Cell Migration During Heart Regeneration in Zebrafish

PubMed Central

Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

2018-01-01

Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, preexisting cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. PMID:27085002

Heart Rate Assessment Immediately after Birth.

PubMed

Phillipos, Emily; Solevåg, Anne Lee; Pichler, Gerhard; Aziz, Khalid; van Os, Sylvia; O'Reilly, Megan; Cheung, Po-Yin; Schmölzer, Georg M

2016-01-01

Heart rate assessment immediately after birth in newborn infants is critical to the correct guidance of resuscitation efforts. There are disagreements as to the best method to measure heart rate. The aim of this study was to assess different methods of heart rate assessment in newborn infants at birth to determine the fastest and most accurate method. PubMed, EMBASE and Google Scholar were systematically searched using the following terms: 'infant', 'heart rate', 'monitoring', 'delivery room', 'resuscitation', 'stethoscope', 'auscultation', 'palpation', 'pulse oximetry', 'electrocardiogram', 'Doppler ultrasound', 'photoplethysmography' and 'wearable sensors'. Eighteen studies were identified that described various methods of heart rate assessment in newborn infants immediately after birth. Studies examining auscultation, palpation, pulse oximetry, electrocardiography and Doppler ultrasound as ways to measure heart rate were included. Heart rate measurements by pulse oximetry are superior to auscultation and palpation, but there is contradictory evidence about its accuracy depending on whether the sensor is connected to the infant or the oximeter first. Several studies indicate that electrocardiogram provides a reliable heart rate faster than pulse oximetry. Doppler ultrasound shows potential for clinical use, however future evidence is needed to support this conclusion. Heart rate assessment is important and there are many measurement methods. The accuracy of routinely applied methods varies, with palpation and auscultation being the least accurate and electrocardiogram being the most accurate. More research is needed on Doppler ultrasound before its clinical use. © 2015 S. Karger AG, Basel.

Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model.

PubMed

Kaese, Sven; Bögeholz, Nils; Pauls, Paul; Dechering, Dirk; Olligs, Jan; Kölker, Katharina; Badawi, Sascha; Frommeyer, Gerrit; Pott, Christian; Eckardt, Lars

2017-08-01

The cardiac sodium/calcium (Na + /Ca 2+ ) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Preattentive processing of heart cues and the perception of heart symptoms in congenital heart disease.

PubMed

Karsdorp, Petra A; Kindt, Merel; Everaerd, Walter; Mulder, Barbara J M

2007-08-01

The present study was aimed at clarifying whether preattentive processing of heart cues results in biased perception of heart sensations in patients with congenital heart disease (ConHD) who are also highly trait anxious. Twenty-six patients with ConHD and 22 healthy participants categorized heart-related (heart rate) or neutral sensations (constant vibration) as either heart or neutral. Both sensations were evoked using a bass speaker that was attached on the chest of the participant. Before each physical sensation, a subliminal heart-related or neutral prime was presented. Biased perception of heart-sensations would become evident by a delayed categorization of the heart-related sensations. In line with the prediction, a combination of high trait anxiety and ConHD resulted in slower responses after a heart-related sensation that was preceded by a subliminal heart cue. Preattentive processing of harmless heart cues may easily elicit overperception of heart symptoms in highly trait anxious patients with ConHD.

Quantifying coordination among the rearfoot, midfoot, and forefoot segments during running.

PubMed

Takabayashi, Tomoya; Edama, Mutsuaki; Yokoyama, Erika; Kanaya, Chiaki; Kubo, Masayoshi

2018-03-01

Because previous studies have suggested that there is a relationship between injury risk and inter-segment coordination, quantifying coordination between the segments is essential. Even though the midfoot and forefoot segments play important roles in dynamic tasks, previous studies have mostly focused on coordination between the shank and rearfoot segments. This study aimed to quantify coordination among rearfoot, midfoot, and forefoot segments during running. Eleven healthy young men ran on a treadmill. The coupling angle, representing inter-segment coordination, was calculated using a modified vector coding technique. The coupling angle was categorised into four coordination patterns. During the absorption phase, rearfoot-midfoot coordination in the frontal planes was mostly in-phase (rearfoot and midfoot eversion with similar amplitudes). The present study found that the eversion of the midfoot with respect to the rearfoot was comparable in magnitude to the eversion of the rearfoot with respect to the shank. A previous study has suggested that disruption of the coordination between the internal rotation of the shank and eversion of the rearfoot leads to running injuries such as anterior knee pain. Thus, these data might be used in the future to compare to individuals with foot deformities or running injuries.

Eotaxin/CCL11 expression by infiltrating macrophages in rat heart transplants during ongoing acute rejection.

PubMed

Zweifel, Martin; Mueller, Christoph; Schaffner, Thomas; Dahinden, Clemens; Matozan, Katja; Driscoll, Robert; Mohacsi, Paul

2009-10-01

Eotaxin/CCL11 chemokine is expressed in different organs, including the heart, but its precise cellular origin in the heart is unknown. Eotaxin is associated with Th2-like responses and exerts its chemotactic effect through the chemokine receptor-3 (CCR3), which is also expressed on mast cells (MC). The aim of our study was to find the cellular origin of eotaxin in the heart, and to assess whether expression is changing during ongoing acute heart transplant rejection, indicating a correlation with mast cell infiltration which we observed in a previous study. In a model of ongoing acute heart transplant rejection in the rat, we found eotaxin mRNA expression within infiltrating macrophages, but not in mast cells, by in situ-hybridization. A five-fold increase in eotaxin protein in rat heart transplants during ongoing acute rejection was measured on day 28 after transplantation, compared to native and isogeneic control hearts. Eotaxin concentrations in donor hearts on day 28 after transplantation were significantly higher compared to recipient hearts, corroborating an origin of eotaxin from cells within the heart, and not from the blood. The quantitative comparison of eotaxin mRNA expression between native hearts, isografts, and allografts, respectively, revealed no statistically significant difference after transplantation, probably due to an overall increase in the housekeeping gene's 18S rRNA during rejection. Quantitative RT-PCR showed an increase in mRNA expression of CCR3, the receptor for eotaxin, during ongoing acute rejection of rat heart allografts. Although a correlation between increasing eotaxin expression by macrophages and mast cell infiltration is suggestive, functional studies will elucidate the role of eotaxin in the process of ongoing acute heart transplant rejection.

The Impact of Worsening Heart Failure in the United States

PubMed Central

Cooper, Lauren B.; DeVore, Adam D.; Felker, G. Michael

2015-01-01

Synopsis In-hospital worsening heart failure represents a clinical scenario in which a patient hospitalized for treatment of acute heart failure experiences a worsening of their condition while in the hospital, requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and post-discharge outcomes. In-hospital worsening heart failure is increasingly being used as an endpoint, or as part of a combined endpoint, in many clinical trials in acute heart failure. This endpoint has advantages over other endpoints commonly used in acute and chronic heart failure trials, such as dyspnea relief and mortality or rehospitalization. Despite the extensive study of this condition, no treatment strategies have been approved for the prevention of this condition. However, several prediction models have been developed to identify worsening heart failure. Continued study in this area is warranted. PMID:26462100

[National disease management guidelines (NVL) for chronic CAD : What is new, what is particularly important?].

PubMed

Werdan, K

2016-09-01

Coronary heart disease (CAD) is widespread and affects 1 in 10 of the population in the age group 40-79 years in Germany. The German national management guidelines on chronic CAD comprise evidence and expert-based recommendations for the diagnostics of chronic stable CAD as well as for interdisciplinary/multidisciplinary therapy and care of patients with stable CAD. The focus is on the diagnostics, prevention, medication therapy, revascularization, rehabilitation, general practitioner care and coordination of care. Recommendations for optimizing cooperation between all medical specialties involved as well as the definition of mandatory and appropriate measures are essential aims of the guidelines both to improve the quality of care and to strengthen the position of the patient.

Construction of a cardiac conduction system subject to extracellular stimulation.

PubMed

Clements, Clyde; Vigmond, Edward

2005-01-01

Proper electrical excitation of the heart is dependent on the specialized conduction system that coordinates the electrical activity from the atria to the ventricles. This paper describes the construction of a conduction system as a branching network of Purkinje fibers on the endocardial surface. Endocardial surfaces were extracted from an FEM model of the ventricles and transformed to 2D. A Purkinje network was drawn on top and the inverse transform performed. The underlying mathematics utilized one dimensional cubic Hermite finite elements. Compared to linear elements, the cubic Hermite solution was found to have a much smaller RMS error. Furthermore, this method has the advantage of enforcing current conservation at bifurcation and unification points, and allows for discrete coupling resistances.

3D Mueller-matrix mapping of biological optically anisotropic networks

NASA Astrophysics Data System (ADS)

Ushenko, O. G.; Ushenko, V. O.; Bodnar, G. B.; Zhytaryuk, V. G.; Prydiy, O. G.; Koval, G.; Lukashevich, I.; Vanchuliak, O.

2018-01-01

The paper consists of two parts. The first part presents short theoretical basics of the method of azimuthally-invariant Mueller-matrix description of optical anisotropy of biological tissues. It was provided experimentally measured coordinate distributions of Mueller-matrix invariants (MMI) of linear and circular birefringences of skeletal muscle tissue. It was defined the values of statistic moments, which characterize the distributions of amplitudes of wavelet coefficients of MMI at different scales of scanning. The second part presents the data of statistic analysis of the distributions of amplitude of wavelet coefficients of the distributions of linear birefringence of myocardium tissue died after the infarction and ischemic heart disease. It was defined the objective criteria of differentiation of the cause of death.

Multiscale polarization diagnostics of birefringent networks in problems of necrotic changes diagnostics

NASA Astrophysics Data System (ADS)

Sakhnovskiy, M. Yu.; Ushenko, Yu. O.; Ushenko, V. O.; Besaha, R. N.; Pavlyukovich, N.; Pavlyukovich, O.

2018-01-01

The paper consists of two parts. The first part presents short theoretical basics of the method of azimuthally-invariant Mueller-matrix description of optical anisotropy of biological tissues. It was provided experimentally measured coordinate distributions of Mueller-matrix invariants (MMI) of linear and circular birefringences of skeletal muscle tissue. It was defined the values of statistic moments, which characterize the distributions of amplitudes of wavelet coefficients of MMI at different scales of scanning. The second part presents the data of statistic analysis of the distributions of amplitude of wavelet coefficients of the distributions of linear birefringence of myocardium tissue died after the infarction and ischemic heart disease. It was defined the objective criteria of differentiation of the cause of death.

Wavelet analysis of birefringence images of myocardium tissue

NASA Astrophysics Data System (ADS)

Sakhnovskiy, M. Yu.; Ushenko, Yu. O.; Kushnerik, L.; Soltys, I. V.; Pavlyukovich, N.; Pavlyukovich, O.

2018-01-01

The paper consists of two parts. The first part presents short theoretical basics of the method of azimuthally-invariant Mueller-matrix description of optical anisotropy of biological tissues. It was provided experimentally measured coordinate distributions of Mueller-matrix invariants (MMI) of linear and circular birefringences of skeletal muscle tissue. It was defined the values of statistic moments, which characterize the distributions of amplitudes of wavelet coefficients of MMI at different scales of scanning. The second part presents the data of statistic analysis of the distributions of amplitude of wavelet coefficients of the distributions of linear birefringence of myocardium tissue died after the infarction and ischemic heart disease. It was defined the objective criteria of differentiation of the cause of death.

Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08).

PubMed

Erdmann, Erland; Charbonnel, Bernard; Wilcox, Robert G; Skene, Allan M; Massi-Benedetti, Massimo; Yates, John; Tan, Meng; Spanheimer, Robert; Standl, Eberhard; Dormandy, John A

2007-11-01

PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) enrolled patients with type 2 diabetes and preexisting cardiovascular disease. These patients were at high risk for heart failure, so any therapeutic benefit could potentially be offset by risk of associated heart failure mortality. We analyzed the heart failure cases to assess the effects of treatment on morbidity and mortality after reports of serious heart failure. PROactive was an outcome study in 5,238 patients randomized to pioglitazone or placebo. Patients with New York Heart Association Class II-IV heart failure at screening were excluded. A serious adverse event of heart failure was defined as heart failure that required hospitalization or prolonged a hospitalization stay, was fatal or life threatening, or resulted in persistent significant disability or incapacity. Heart failure risk was evaluated by multivariate regression. More pioglitazone (5.7%) than placebo patients (4.1%) had a serious heart failure event during the study (P = 0.007). However, mortality due to heart failure was similar (25 of 2,605 [0.96%] for pioglitazone vs. 22 of 2,633 [0.84%] for placebo; P = 0.639). Among patients with a serious heart failure event, subsequent all-cause mortality was proportionately lower with pioglitazone (40 of 149 [26.8%] vs. 37 of 108 [34.3%] with placebo; P = 0.1338). Proportionately fewer pioglitazone patients with serious heart failure went on to have an event in the primary (47.7% with pioglitazone vs. 57.4% with placebo; P = 0.0593) or main secondary end point (34.9% with pioglitazone vs. 47.2% with placebo; P = 0.025). Although the incidence of serious heart failure was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with serious heart failure.

Heart rate variability alterations in late life depression: A meta-analysis.

PubMed

Brown, Lydia; Karmakar, Chandan; Gray, Richard; Jindal, Ripu; Lim, Terrence; Bryant, Christina

2018-08-01

There is strong evidence for a bi-directional relationship between heart-health and depression in later life, but the physiological mechanisms underlying this relationship remain unclear. Heart rate variability is one promising factor that might help explain this relationship. We present results of a meta-analysis that considers heart rate variability alterations in older adults with depression. Literature search of Embase, PsychInfo and Medline revealed five clinical studies and six observational studies that examined the relationship between heart rate variability and depression in adults with a mean age over 60. These studies were included in this meta-analysis. Heart rate variability was reduced among older adults with clinical depression (N = 550), relative to healthy controls (Hedges' g = -0.334, 95%CI [-0.579, -0.090], p = .007). When high-frequency and low-frequency heart rate variability were investigated separately, only low-frequency heart rate variability was significantly reduced in depressed patients (Hedges' g = -0.626, 95%CI [-1.083, -0.169], p = .007). A similar but weaker pattern of results was found in the observational studies. Most findings remained significant among unmedicated depressed older adults. Evidence of effect-size heterogeneity was found in the clinical studies, indicating the need for more well-designed research in the area. Heart rate variability is reduced among older adults with depression, and this effect is not fully attributable to antidepressant medication use. Specifically, low-frequency heart rate variability may be reduced in depressed older adults. Heart rate variability warrants further attention, as it could help inform research into the prevention and treatment of depression in later life. Copyright © 2018 Elsevier B.V. All rights reserved.

Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis.

PubMed

Wu, Pensée; Haththotuwa, Randula; Kwok, Chun Shing; Babu, Aswin; Kotronias, Rafail A; Rushton, Claire; Zaman, Azfar; Fryer, Anthony A; Kadam, Umesh; Chew-Graham, Carolyn A; Mamas, Mamas A

2017-02-01

Preeclampsia is a pregnancy-specific disorder resulting in hypertension and multiorgan dysfunction. There is growing evidence that these effects persist after pregnancy. We aimed to systematically evaluate and quantify the evidence on the relationship between preeclampsia and the future risk of cardiovascular diseases. We studied the future risk of heart failure, coronary heart disease, composite cardiovascular disease, death because of coronary heart or cardiovascular disease, stroke, and stroke death after preeclampsia. A systematic search of MEDLINE and EMBASE was performed to identify relevant studies. We used random-effects meta-analysis to determine the risk. Twenty-two studies were identified with >6.4 million women including >258 000 women with preeclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that preeclampsia was independently associated with an increased risk of future heart failure (risk ratio [RR], 4.19; 95% confidence interval [CI], 2.09-8.38), coronary heart disease (RR, 2.50; 95% CI, 1.43-4.37), cardiovascular disease death (RR, 2.21; 95% CI, 1.83-2.66), and stroke (RR, 1.81; 95% CI, 1.29-2.55). Sensitivity analyses showed that preeclampsia continued to be associated with an increased risk of future coronary heart disease, heart failure, and stroke after adjusting for age (RR, 3.89; 95% CI, 1.83-8.26), body mass index (RR, 3.16; 95% CI, 1.41-7.07), and diabetes mellitus (RR, 4.19; 95% CI, 2.09-8.38). Preeclampsia is associated with a 4-fold increase in future incident heart failure and a 2-fold increased risk in coronary heart disease, stroke, and death because of coronary heart or cardiovascular disease. Our study highlights the importance of lifelong monitoring of cardiovascular risk factors in women with a history of preeclampsia. © 2017 American Heart Association, Inc.

A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects

PubMed Central

Hempel, Annemarie; Kühl, Michael

2016-01-01

The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques. PMID:29367567

Isolated heart models: cardiovascular system studies and technological advances.

PubMed

Olejnickova, Veronika; Novakova, Marie; Provaznik, Ivo

2015-07-01

Isolated heart model is a relevant tool for cardiovascular system studies. It represents a highly reproducible model for studying broad spectrum of biochemical, physiological, morphological, and pharmaceutical parameters, including analysis of intrinsic heart mechanics, metabolism, and coronary vascular response. Results obtained in this model are under no influence of other organ systems, plasma concentration of hormones or ions and influence of autonomic nervous system. The review describes various isolated heart models, the modes of heart perfusion, and advantages and limitations of various experimental setups. It reports the improvements of perfusion setup according to Langendorff introduced by the authors.

[Atrial fibrillation as a comorbidity of heart failure].

PubMed

Wachter, R

2018-05-01

Atrial fibrillation and heart failure are diseases that frequently occur together in patients, and the prevalence of the two diseases will continue to increase in the future. Unfortunately, they exacerbate each other: the prognosis of patients with atrial fibrillation is poorer if there is heart failure, and the prognosis of heart failure patients with atrial fibrillation is poorer than the prognosis of heart failure patients without atrial fibrillation. In the past, studies on drug stabilization of sinus rhythm with antiarrhythmic drugs were not able to show any influence on the prognosis of patients. In these patients, it seems to be better to treat the atrial fibrillation interventionally. The CASTLE-AF study has just shown for the first time that isolation of the pulmonary vein to treat atrial fibrillation in heart failure patients has positive effects: hospital admissions for heart failure decreased and the overall survival improved. Further studies have shown that quality of life improves and performance is increased.

Micro practices of coordination based on complex adaptive systems: user needs and strategies for coordinating public health in Denmark.

PubMed

Terkildsen, Morten Deleuran; Wittrup, Inge; Burau, Viola

2015-01-01

Many highly formalised approaches to coordination poorly fit public health and recent studies call for coordination based on complex adaptive systems. Our contribution is two-fold. Empirically, we focus on public health, and theoretically we build on the patient perspective and treat coordination as a process of contingent, two-level negotiations of user needs. The paper draws on the concept of user needs-based coordination and sees coordination as a process, whereby needs emerging from the life world of the user are made amenable to the health system through negotiations. The analysis is based on an explorative case study of a health promotion initiative in Denmark. It adopts an anthropological qualitative approach and uses a range of qualitative data. The analysis identifies four strategies of coordination: the coordinator focusing on the individual user or on relations with other professionals; and the manager coaching the coordinator or providing structural support. Crucially, the coordination strategies by management remain weak as they do not directly relate to specific user needs. In process of bottom-up negotiations user needs become blurred and this is especially a challenge for management. The study therefore calls for an increased focus on the level nature of negotiations to bridge the gap that currently weakens coordination strategies by management.

Coordination success and interpersonal perceptions: matching versus mismatching.

PubMed

Abele, Susanne; Stasser, Garold

2008-09-01

Coordination is an essential part of social functioning. The authors distinguish 2 types of coordination: matching and mismatching. In matching, coordination is successful if parties choose the same action. In mismatching, coordination is successful if people choose different actions. In 3 studies, the authors investigated the downstream social consequences of tacit coordination for interpersonal perceptions. In all studies, participants repeatedly choose between 2 bets with equivalent expected values, and payoffs increased either when they choose the same bet or when they choose different bets. In the 1st 2 studies, coordination success increased the perceptions of interpersonal similarity and liking when matching was required but not when mismatching was required. The authors' interpretation is that matching responses and coordination success had countervailing effects in the mismatching task. Also, percentage of matched responses did not affect perceptions when coordination was not required (Experiment 2). In 4 person teams, a frequently matching partner was viewed more favorably (smarter, more similar to self, and more liked) than were other teammates, even when mismatching increased payoffs (Experiment 3).

Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

PubMed Central

Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

2016-01-01

Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

Congenital heart defects in cats: A retrospective study of 162 cats (1996-2013).

PubMed

Tidholm, Anna; Ljungvall, Ingrid; Michal, Jenny; Häggström, Jens; Höglund, Katja

2015-12-01

To study the prevalence and distribution of congenital heart defects in cats presented at two referral centers in Sweden between 1996 and 2013. 162 client-owned cats with congenital heart defects. Case records of cats diagnosed with congenital heart disease were reviewed retrospectively. The overall prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. A total of 182 heart defects were identified as 16 cats were diagnosed with more than one defect. Ventricular septal defect (VSD) was most prevalent, found in 50% of cats, followed by tricuspid valve dysplasia (11%), pulmonic stenosis (10%), atrial septal defect (10%), aortic stenosis (9%), mitral valve dysplasia (9%), tetralogy of Fallot (5%), patent ductus arteriosus (3%), common atrioventricular canal (2%), and the following defects that each accounted for 0.6% of cats: double chamber right ventricle, double outlet right ventricle, endocardial fibroelastosis, dextroposition of the aorta, persistent right aortic arch, and pulmonary atresia. The prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. Ventricular septal defect was the most common congenital heart defect in this study. Copyright © 2014 Elsevier B.V. All rights reserved.

A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

PubMed

Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

2018-03-20

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

Quantification of the uncertainty in coronary CTA plaque measurements using dynamic cardiac phantom and 3D-printed plaque models

NASA Astrophysics Data System (ADS)

Richards, Taylor; Sturgeon, Gregory M.; Ramirez-Giraldo, Juan Carlos; Rubin, Geoffrey; Segars, Paul; Samei, Ehsan

2017-03-01

The purpose of this study was to quantify the accuracy of coronary computed tomography angiography (CTA) stenosis measurements using newly developed physical coronary plaque models attached to a base dynamic cardiac phantom (Shelley Medical DHP-01). Coronary plaque models (5 mm diameter, 50% stenosis, and 32 mm long) were designed and 3D-printed with tissue equivalent materials (calcified plaque with iodine enhanced lumen). Realistic cardiac motion was achieved by fitting known cardiac motion vectors to left ventricle volume-time curves to create synchronized heart motion profiles executed by the base cardiac phantom. Realistic coronary CTA acquisition was accomplished by synthesizing corresponding ECG waveforms for gating and reconstruction purposes. All scans were acquired using a retrospective gating technique on a dual-source CT system (Siemens SOMATOM FLASH) with 75ms temporal resolution. Multi-planar reformatted images were reconstructed along vessel centerlines and the enhanced lumens were manually segmented by 5 independent operators. On average, the stenosis measurement accuracy was 0.9% positive bias for the motion free condition (0 bpm). The measurement accuracy monotonically decreased to 18.5% negative bias at 90 bpm. Contrast-tonoise (CNR), vessel circularity, and segmentation conformity also decreased monotonically with increasing heart rate. These results demonstrate successful implementation of the base cardiac phantom with 3D-printed coronary plaque models, adjustable motion profiles, and coordinated ECG waveforms. They further show the utility of the model to ascertain metrics of coronary CT accuracy and image quality under a variety of plaque, motion, and acquisition conditions.

Liver transplantation in Japan.

PubMed

Soyama, Akihiko; Eguchi, Susumu; Egawa, Hiroto

2016-10-01

As of December 31, 2014, 7937 liver transplants (7673 living donor transplants and 264 deceased donor liver transplantations [DDLTs; 261 from heart-beating donors and 3 from non-heart-beating donors]) have been performed in 67 institutions in Japan. The revised Organ Transplant Law in Japan came into effect in July 2010, which allows organ procurement from brain-dead individuals, including children, with family consent if the patient had not previously refused organ donation. However, the number of deceased donor organ donations has not increased as anticipated. The rate of deceased organ donations per million population (pmp) has remained at less than 1. To maximize the viability of the limited numbers of donated organs, a system has been adopted that includes the partnership of well-trained transplant consultant doctors and local doctors. For compensating for the decreased opportunity of on-site training, an educational system regarding quality organ procurement for transplant surgeons has also been established. Furthermore, experts in the field of liver transplantation are currently discussing adoption of the Model for End-Stage Liver Disease score for allocation, promoting split-liver transplantation, arranging in-house coordinators, and improving the frequency of proposing the option to donate organs to the families. To overcome the shortage of donors during efforts to promote organ donation, living donor liver transplantation (LDLT) has been developed in Japan. Continuous efforts to increase DDLT in addition to the successful experience of LDLT will increase the benefits of liver transplantation for more patients. Liver Transplantation 22 1401-1407 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus.

PubMed

Shepherd, Danielle L; Hathaway, Quincy A; Nichols, Cody E; Durr, Andrya J; Pinti, Mark V; Hughes, Kristen M; Kunovac, Amina; Stine, Seth M; Hollander, John M

2018-06-01

>99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor. Type 2 diabetes mellitus (T2DM) disrupts mitochondrial proteomic signature which is associated with decreased protein import efficiency. The goal of this study was to manipulate the mitochondrial protein import process through targeted restoration of mtHsp70, in an effort to restore proteomic signature and mitochondrial function in the T2DM heart. A novel line of cardiac-specific mtHsp70 transgenic mice on the db/db background were generated and cardiac mitochondrial subpopulations were isolated with proteomic evaluation and mitochondrial function assessed. MicroRNA and epigenetic regulation of the mtHsp70 gene during T2DM were also evaluated. MtHsp70 overexpression restored cardiac function and nuclear-encoded mitochondrial protein import, contributing to a beneficial impact on proteome signature and enhanced mitochondrial function during T2DM. Further, transcriptional repression at the mtHsp70 genomic locus through increased localization of H3K27me3 during T2DM insult was observed. Our results suggest that restoration of a key protein import constituent, mtHsp70, provides therapeutic benefit through attenuation of mitochondrial and contractile dysfunction in T2DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

Describing care coordination of gynecologic oncology in western healthcare settings: a rapid review.

PubMed

Grant, Sean; Motala, Aneesa; Chrystal, Joya G; Shanman, Roberta; Zuchowski, Jessica; Zephyrin, Laurie; Cordasco, Kristina M

2018-05-23

Caring for women with gynecologic malignancies requires multidisciplinary communication and coordination across multiple providers. This article discusses a rapid review of the literature on characteristics of care coordination for gynecologic malignancies. Five electronic databases (from inception through March 2015) were searched for empirical studies on coordinated care models for female adults with gynecologic malignancies. A single reviewer extracted and synthesized information on how care was coordinated, how care teams made decisions, who performed what tasks, how care teams communicated information to coordinate care, and potential impact of the characteristic on delivering coordinated care. From 26 included studies, predominant characteristics of coordinated care were identified: multidisciplinary teams, patient navigators, scheduled follow-ups, survivorship care plans, and colocated services. Decision-making was best documented for studies that utilized teams that had periodic scheduled meetings with set agendas and consistent procedures. Providers' roles in coordinating care were numerous, reflecting professional backgrounds: oncologists had most authority in making treatment decisions; radiologists and pathologists shared vital biomedical information; and nurses coordinated care and communicated with patients. Communication tools and strategies across studies included having shared medical records, integrated treatment plans, and telephone-based or teleconferencing communication. There was limited information available on the impact of characteristics and accompanying strategies or tools. Several characteristics of care coordination models for gynecologic cancers have been published in the literature. Further investigation is needed to understand the relative effectiveness of these ways to coordinate care.

A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

PubMed

Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

2016-10-01

Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure

PubMed Central

Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

2016-01-01

Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease. PMID:27703506

Frailty Assessment in Heart Failure: an Overview of the Multi-domain Approach.

PubMed

McDonagh, Julee; Ferguson, Caleb; Newton, Phillip J

2018-02-01

The study aims (1) to provide a contemporary description of frailty assessment in heart failure and (2) to provide an overview of multi-domain frailty assessment in heart failure. Frailty assessment is an important predictive measure for mortality and hospitalisation in individuals with heart failure. To date, there are no frailty assessment instruments validated for use in heart failure. This has resulted in significant heterogeneity between studies regarding the assessment of frailty. The most common frailty assessment instrument used in heart failure is the Frailty Phenotype which focuses on five physical domains of frailty; the appropriateness a purely physical measure of frailty in individuals with heart failure who frequently experience decreased exercise tolerance and shortness of breath is yet to be determined. A limited number of studies have approached frailty assessment using a multi-domain view which may be more clinically relevant in heart failure. There remains a lack of consensus regarding frailty assessment and an absence of a validated instrument in heart failure. Despite this, frailty continues to be assessed frequently, primarily for research purposes, using predominantly physical frailty measures. A more multidimensional view of frailty assessment using a multi-domain approach will likely be more sensitive to identifying at risk patients.

Inpatient Utilization and Costs for Medicare Fee-for-Service Beneficiaries with Heart Failure.

PubMed

Fitch, Kathryn; Pelizzari, Pamela M; Pyenson, Bruce

2016-04-01

Although the medical and economic burden of heart failure in the United States is already substantial, it will likely grow as the population ages and life expectancy increases. Not surprisingly, most of the heart failure burden is borne by individuals aged ≥65 years, many of whom are in the Medicare population. The population-based utilization and costs of inpatient care for Medicare beneficiaries with heart failure are not well understood by payers and providers. To create a real-world view of utilization and costs associated with inpatient admissions, readmissions, and admissions to skilled nursing facilities among Medicare fee-for-service (FFS) beneficiaries with heart failure. The study used the 2011 and 2012 Medicare 5% sample limited data set to perform a retrospective analysis of claims data. The look-back year that was used to identify certain patient characteristics was 2011, and 2012 was the analysis period for the study. Beneficiaries with heart failure were defined as those who had ≥1 acute inpatient, emergency department, nonacute inpatient, or outpatient claims in 2012 containing an International Classification of Diseases, Ninth Revision code for heart failure. To be included in the study, beneficiaries with heart failure had to have eligibility for ≥1 months in 2012 and in all 2011 months, with Part A and Part B eligibility in all the study months, and no enrollment in an HMO (Medicare Advantage plan). Utilization of inpatient admissions, inpatient readmissions, and skilled nursing facility admissions in 2012 were reported for Medicare FFS beneficiaries with heart failure and for all Medicare FFS beneficiaries. The costs for key metrics included all allowed Medicare payments in 2012 US dollars. The 2012 Medicare FFS population for this study consisted of 1,461,935 patients (1,301,545 without heart failure; 160,390 with heart failure); the heart failure prevalence was 11%. The Medicare-allowed cost per member per month (PMPM) was $3395 for a patient with heart failure, whereas the allowed cost for the total Medicare population was $1045 PMPM. The Medicare-allowed amounts for the population with heart failure accounted for 34% of the total annual Medicare FFS population-allowed amounts. The heart failure population constituted 41.5%, 55.3%, and 49.5% of total Medicare FFS inpatient admissions, readmissions, and admissions to skilled nursing facilities, respectively. The costs of inpatient admissions, readmissions, and admissions to skilled nursing facilities among the heart failure population contributed $182 PMPM (17.5%), $58 PMPM (5.6%), and $46 PMPM (4.4%), respectively, to the total Medicare FFS population-allowed cost of $1045 PMPM. Medicare FFS beneficiaries with heart failure have high inpatient admission and readmission rates and generate substantial costs. Because a substantial portion of all inpatient admissions are for Medicare beneficiaries with heart failure, it is reasonable for hospitals in Medicare accountable care organizations to focus on more aggressive post-acute care management, including a focus on reducing readmissions for the population with heart failure. Our study findings highlight areas of high service utilization and cost for Medicare patients with heart failure that can be of value to Medicare, Medicare Advantage plans, and providers.

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

The Association between Childhood Physical Abuse and Heart Disease in Adulthood: Findings from a Representative Community Sample

ERIC Educational Resources Information Center

Fuller-Thomson, Esme; Brennenstuhl, Sarah; Frank, John

2010-01-01

Objectives: Although, the relationship between childhood physical abuse and adult heart disease has been documented, very few studies have controlled for many of the known risk factors for heart disease. The objective of the current study, therefore, was to investigate the association between childhood physical abuse and adult heart disease while…

D Coordinate Transformation Using Artificial Neural Networks

NASA Astrophysics Data System (ADS)

Konakoglu, B.; Cakır, L.; Gökalp, E.

2016-10-01

Two coordinate systems used in Turkey, namely the ED50 (European Datum 1950) and ITRF96 (International Terrestrial Reference Frame 1996) coordinate systems. In most cases, it is necessary to conduct transformation from one coordinate system to another. The artificial neural network (ANN) is a new method for coordinate transformation. One of the biggest advantages of the ANN is that it can determine the relationship between two coordinate systems without a mathematical model. The aim of this study was to investigate the performances of three different ANN models (Feed Forward Back Propagation (FFBP), Cascade Forward Back Propagation (CFBP) and Radial Basis Function Neural Network (RBFNN)) with regard to 2D coordinate transformation. To do this, three data sets were used for the same study area, the city of Trabzon. The coordinates of data sets were measured in the ED50 and ITRF96 coordinate systems by using RTK-GPS technique. Performance of each transformation method was investigated by using the coordinate differences between the known and estimated coordinates. The results showed that the ANN algorithms can be used for 2D coordinate transformation in cases where optimum model parameters are selected.

Critical diversity: Divided or united states of social coordination

PubMed Central

Kelso, J. A. Scott; Tognoli, Emmanuelle

2018-01-01

Much of our knowledge of coordination comes from studies of simple, dyadic systems or systems containing large numbers of components. The huge gap ‘in between’ is seldom addressed, empirically or theoretically. We introduce a new paradigm to study the coordination dynamics of such intermediate-sized ensembles with the goal of identifying key mechanisms of interaction. Rhythmic coordination was studied in ensembles of eight people, with differences in movement frequency (‘diversity’) manipulated within the ensemble. Quantitative change in diversity led to qualitative changes in coordination, a critical value separating régimes of integration and segregation between groups. Metastable and multifrequency coordination between participants enabled communication across segregated groups within the ensemble, without destroying overall order. These novel findings reveal key factors underlying coordination in ensemble sizes previously considered too complicated or 'messy' for systematic study and supply future theoretical/computational models with new empirical checkpoints. PMID:29617371

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

PubMed Central

Castoe, Todd A.; de Koning, A. P. Jason; Hall, Kathryn T.; Card, Daren C.; Schield, Drew R.; Fujita, Matthew K.; Ruggiero, Robert P.; Degner, Jack F.; Daza, Juan M.; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J.; Castoe, Jill M.; Fox, Samuel E.; Poole, Alex W.; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W.; Li, Qing; Schott, Ryan K.; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A.; Hoffmann, Federico G.; Bogden, Robert; Smith, Eric N.; Chang, Belinda S. W.; Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Richardson, Michael K.; Mackessy, Stephen P.; Bronikowski, Anne M.; Yandell, Mark; Warren, Wesley C.; Secor, Stephen M.; Pollock, David D.

2013-01-01

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome. PMID:24297902

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

PubMed

Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

2013-12-17

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

A systematic review of trends and patterns of congenital heart disease in children in Nigeria from 1964-2015.

PubMed

Abdulkadir, Mohammed; Abdulkadir, Zainab

2016-06-01

Congenital heart diseases cause significant childhood morbidity and mortality. Several restricted studies have been conducted on the epidemiology in Nigeria. No truly nationwide data on patterns of congenital heart disease exists. To determine the patterns of congenital heart disease in children in Nigeria and examine trends in the occurrence of individual defects across 5 decades. We searched PubMed database, Google scholar, TRIP database, World Health Organisation libraries and reference lists of selected articles for studies on patterns of congenital heart disease among children in Nigeria between 1964 and 2015. Two researchers reviewed the papers independently and extracted the data. Seventeen studies were selected that included 2,953 children with congenital heart disease. The commonest congenital heart diseases in Nigeria are ventricular septal defect (40.6%), patent ductus arteriosus (18.4%), atrial septal defect (11.3%) and tetralogy of Fallot (11.8%). There has been a 6% increase in the burden of VSD in every decade for the 5 decades studied and a decline in the occurrence of pulmonary stenosis. Studies conducted in Northern Nigeria demonstrated higher proportions of atrial septal defects than patent ductus arteriosus. Ventricular septal defects are the commonest congenital heart diseases in Nigeria with a rising burden.

National Decline in Donor Heart Utilization With Regional Variability: 1995–2010

PubMed Central

Khush, K. K.; Zaroff, J. G.; Nguyen, J.; Menza, R.; Goldstein, B. A.

2015-01-01

The severe shortage of donor hearts limits the availability of transplantation for the growing population of patients with end-stage heart disease. We examined national trends in donor heart acceptance for transplant. OPTN data were analyzed for all potential adult cardiac organ donors between 1995 and 2010. Donor heart disposition was categorized as transplanted, declined for transplant or other. We studied changes in the probability of donor heart acceptance according to demographic and clinical characteristics, nationwide and by UNOS region. Of 82 053 potential donor hearts, 34% were accepted and 48% were declined (18% used for other purposes). There was a significant decrease in donor heart acceptance from 44% in 1995 to 29% in 2006, and subsequent increase to 32% in 2010. Older donor age, female sex and medical co-morbidities predicted non-acceptance. Donor age and co-morbidities increased during the study period, with a concomitant decrease in acceptance of hearts from donors with undesirable characteristics. Overall, predictors of heart non-use were similar across UNOS regions, although utilization varied between regions. Regional variation suggests a potential to improve heart acceptance rates in under-performing regions, and supports research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance for transplantation. PMID:25676093

Comparative study of myocardial high energy phosphate substrate content in slow and fast growing chicken and in chickens with heart failure and ascites.

PubMed

Olkowski, A A; Nain, S; Wojnarowicz, C; Laarveld, B; Alcorn, J; Ling, B B

2007-09-01

In order to explain the biochemical mechanisms associated with deteriorating heart function in broiler chickens, this study compared myocardial high energy phosphate substrates in leghorns, feed restricted (Broilers-Res) broilers, ad libitum fed broilers (Broilers-AL), and in broilers that developed heart failure and ascites. The profile of adenine nucleotide content in the heart tissue did not differ between leghorns and Broilers-Res, but there were significant differences among Broilers-Res, Broilers-AL, and broilers with ascites. During intensive growth periods, leghorns and Broilers-Res showed increasing trends in heart ATP levels, whereas in fast growing broilers the heart ATP declined (p<0.021). ATP:ADP and ATP:CrP ratios increased with age in both leghorn and Broilers-Res, declined in fast growing broilers, and were the lowest in broilers that developed heart failure. The changes in heart high energy phosphate profile in broilers suggest that the energy demand of the heart during a rapid growth phase may exceed the bird's metabolic capacity to supply adequate levels of high energy phosphate substrate. The insufficiency of energy substrate likely contributes to the declining heart rate. In some individuals this may lead to impaired heart pump function, and in more severe cases may progress to heart pump failure.

Cell migration during heart regeneration in zebrafish.

PubMed

Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

2016-07-01

Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, pre-existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. Developmental Dynamics 245:774-787, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Unique challenges of hospice for patients with heart failure: A qualitative study of hospice clinicians.

PubMed

Lum, Hillary D; Jones, Jacqueline; Lahoff, Dana; Allen, Larry A; Bekelman, David B; Kutner, Jean S; Matlock, Daniel D

2015-09-01

Patients with heart failure have end-of-life care needs that may benefit from hospice care. The goal of this descriptive study was to understand hospice clinicians' perspectives on the unique aspects of caring for patients with heart failure to inform approaches to improving end-of-life care. This qualitative study explored experiences, observations, and perspectives of hospice clinicians regarding hospice care for patients with heart failure. Thirteen hospice clinicians from a variety of professional disciplines and clinical roles, diverse geographic regions, and varying lengths of time working in hospice participated in semistructured interviews. Through team-based, iterative qualitative analysis, we identified 3 major themes. Hospice clinicians identified 3 themes regarding care for patients with heart failure. First, care for patients with heart failure involves clinical complexity and a tailored approach to cardiac medications and advanced cardiac technologies. Second, hospice clinicians describe the difficulty patients with heart failure have in trusting hospice care due to patient optimism, prognostic uncertainty, and reliance on prehospice health care providers. Third, hospice clinicians described opportunities to improve heart failure-specific hospice care, highlighting the desire for collaboration with referring cardiologists. From a hospice clinician perspective, caring for patients with heart failure is unique compared with other hospice populations. This study suggests potential opportunities for hospice clinicians and referring providers who seek to collaborate to improve care for patients with heart failure during the transition to hospice care. Published by Elsevier Inc.

Heart rate as an independent risk factor in patients with multiple organ dysfunction: a prospective, observational study.

PubMed

Hoke, Robert S; Müller-Werdan, Ursula; Lautenschläger, Christine; Werdan, Karl; Ebelt, Henning

2012-02-01

To study the association between baseline heart rate and outcome in patients with multiple organ dysfunction (MODS) as well as the course of heart rate over the first 4 days during MODS. Prospective observational study in 89 patients with MODS, defined as an APACHE-II score ≥20. Baseline heart rate (HR(0)) was determined over a 60-minute period at the time of MODS diagnosis. 28-day all-cause mortality was the primary endpoint of the study, a fall of the APACHE-II score by 4 points or more from day 0 to day 4 constituted the secondary endpoint. Hazard ratios for heart rate of 90 beats per minute (bpm) or greater relative to less than 90 bpm were calculated using Cox proportional hazards model and adjusted for confounding variables. Median baseline heart rate was 83 bpm in survivors and 92 bpm in non-survivors (p = 0.048). 28-day mortality was 32 and 61% in patients with HR(0) < 90 bpm and HR(0) ≥ 90 bpm, respectively. The adjusted hazard ratio for 28-day mortality was 2.30 (95% confidence interval 1.21-4.36, p = 0.001) for HR(0) ≥ 90 bpm relative to HR(0) < 90 bpm. No correlation was found between baseline heart rate and the secondary endpoint. From day 0 to day 4, heart rate remained elevated in all patients, as well as in survivors and non-survivors. A heart rate ≥90 bpm at the time of MODS diagnosis is an independent risk factor for increased 28-day mortality. As in patients with cardiovascular conditions such as coronary heart disease or chronic heart failure, heart rate might constitute a target for heart rate-lowering therapy in the narrow initial treatment window of MODS.

Models of torsades de pointes: effects of FPL64176, DPI201106, dofetilide, and chromanol 293B in isolated rabbit and guinea pig hearts.

PubMed

Cheng, Hsien C; Incardona, Josephine

2009-01-01

For studying the torsades de pointes (TdP) liability of a compound, most high and medium throughput methods use surrogate markers such as HERG inhibition and QT prolongation. In this study, we have tested whether isolated hearts may be modified to allow TdP to be the direct readout. Isolated spontaneously beating rabbit and guinea pig hearts were perfused according to the Langendorff method in hypokalemic (2.1 mM) solution. The in vitro lead II ECG equivalent and the incidence of TdP were monitored for 1 h. In addition, heart rate, QTc, Tp-Te, short-term variability (STV), time to arrhythmia, and time to TdP were also analyzed. FPL64176, a calcium channel activator; and DPI201106, a sodium channel inactivation inhibitor, produced TdP in isolated rabbit and guinea pig hearts in a concentration dependent manner; guinea pig hearts were 3- to 5-fold more sensitive than rabbit hearts. Both compounds also increased QTc and STV. In contrast, dofetilide, an IKr inhibitor, produced no (or a low incidence of) TdP in both species, in spite of prolongation of QTc intervals. Chromanol 293B, an IKs inhibitor, did not produce TdP in rabbit hearts but elicited TdP concentration dependently in guinea pig hearts even though the compound had no effect on QTc intervals. IKs inhibition appears to be more likely to produce TdP in isolated guinea pig hearts than IKr inhibition. Chromanol 293B did not produce TdP in rabbit hearts presumably due to a low level of IKs channels in the heart. TdP produced in this study was consistent with the notion that its production was a consequence of reduced repolarization reserve, thereby causing rhythmic abnormalities. This isolated, perfused, and spontaneously beating rabbit and guinea pig heart preparation in hypokalemic medium may be useful as a preclinical test model for studying proarrhythmic liability of compounds in new drug development.

The Failing Heart Relies on Ketone Bodies as a Fuel.

PubMed

Aubert, Gregory; Martin, Ola J; Horton, Julie L; Lai, Ling; Vega, Rick B; Leone, Teresa C; Koves, Timothy; Gardell, Stephen J; Krüger, Marcus; Hoppel, Charles L; Lewandowski, E Douglas; Crawford, Peter A; Muoio, Deborah M; Kelly, Daniel P

2016-02-23

Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. Quantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of β-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified. These results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure. © 2016 American Heart Association, Inc.

Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study.

PubMed

Wang, Yan; Cao, Li; Liang, Dong; Meng, Lulu; Wu, Yun; Qiao, Fengchang; Ji, Xiuqing; Luo, Chunyu; Zhang, Jingjing; Xu, Tianhui; Yu, Bin; Wang, Leilei; Wang, Ting; Pan, Qiong; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng

2018-02-01

Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort. Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease. In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period. Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05). Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

The epicardium signals the way towards heart regeneration

PubMed Central

Masters, Megan; Riley, Paul R.

2014-01-01

From historical studies of developing chick hearts to recent advances in regenerative injury models, the epicardium has arisen as a key player in heart genesis and repair. The epicardium provides paracrine signals to nurture growth of the developing heart from mid-gestation, and epicardium-derived cells act as progenitors of numerous cardiac cell types. Interference with either process is terminal for heart development and embryogenesis. In adulthood, the dormant epicardium reinstates an embryonic gene programme in response to injury. Furthermore, injury-induced epicardial signalling is essential for heart regeneration in zebrafish. Given these critical roles in development, injury response and heart regeneration, the application of epicardial signals following adult heart injury could offer therapeutic strategies for the treatment of ischaemic heart disease and heart failure. PMID:24933704

Pharmacological heart rate lowering in patients with a preserved ejection fraction-review of a failing concept.

PubMed

Meyer, Markus; Rambod, Mehdi; LeWinter, Martin

2018-07-01

Epidemiological studies have demonstrated that high resting heart rates are associated with increased mortality. Clinical studies in patients with heart failure and reduced ejection fraction have shown that heart rate lowering with beta-blockers and ivabradine improves survival. It is therefore often assumed that heart rate lowering is beneficial in other patients as well. Here, we critically appraise the effects of pharmacological heart rate lowering in patients with both normal and reduced ejection fraction with an emphasis on the effects of pharmacological heart rate lowering in hypertension and heart failure. Emerging evidence from recent clinical trials and meta-analyses suggest that pharmacological heart rate lowering is not beneficial in patients with a normal or preserved ejection fraction. This has just begun to be reflected in some but not all guideline recommendations. The detrimental effects of pharmacological heart rate lowering are due to an increase in central blood pressures, higher left ventricular systolic and diastolic pressures, and increased ventricular wall stress. Therefore, we propose that heart rate lowering per se reproduces the hemodynamic effects of diastolic dysfunction and imposes an increased arterial load on the left ventricle, which combine to increase the risk of heart failure and atrial fibrillation. Pharmacologic heart rate lowering is clearly beneficial in patients with a dilated cardiomyopathy but not in patients with normal chamber dimensions and normal systolic function. These conflicting effects can be explained based on a model that considers the hemodynamic and ventricular structural effects of heart rate changes.

Heart in anatomy history, radiology, anthropology and art.

PubMed

Marinković, S; Lazić, D; Kanjuh, V; Valjarević, S; Tomić, I; Aksić, M; Starčević, A

2014-05-01

Anthropologic, artistic and medical significance of heart inspired usto undertake this multidisciplinary study. Amongst the 24 obtained echocardiograms and phonograms, 1 was used for a Photoshop processing. In addition, over 20,000 art work reproductions were examined in this study. Artistic and symbolic presentation of heart started some 15,000 years ago. First heart models were made by the Egyptian and Olmec civilisations. Ancient cultures regarded heart as the seat of the soul, spirit and intelligence. First anatomical and artistic images of heart were created by Leonardo da Vinci in the15th century, and first wax models by the Italian anatomists in the 17th century. Mediaeval religious symbolism of heart was replaced in the Renaissance and later on mainly by its role in the romantic love. Anatomical heart art continued in the 18th and 19th centuries through the works of Sénac, Cloquet, Hirschfeldand Bourgery. Some modern artists, such as Dalí, Kahlo, Rivera, Warhol, Ivanjicki, Vital, Kober and Mastrlova, created the anatomical heart images or sculptures, whereas some others, such as Duchamp, Klee, Miró, Matisse and Dine, presented heart symbol in their artworks. New radiologic technologies produce fine images of heart, some of which are similar to the works of modern artists. Heart biology and symbolism have had a tremendous influence on our culture, including art and medical sciences. New radiologic techniques and computer technology have produced such images of heart, which substantially improved diagnosis, but also enhanced the heart aesthetics.

Update for 2014 on clinical cardiology, geriatric cardiology, and heart failure and transplantation.

PubMed

Barón-Esquivias, Gonzalo; Manito, Nicolás; López Díaz, Javier; Martín Santana, Antonio; García Pinilla, José Manuel; Gómez Doblas, Juan José; Gómez Bueno, Manuel; Barrios Alonso, Vivencio; Lambert, José Luis

2015-04-01

In the present article, we review publications from the previous year in the following 3 areas: clinical cardiology, geriatric cardiology, and heart failure and transplantation. Among the new developments in clinical cardiology are several contributions from Spanish groups on tricuspid and aortic regurgitation, developments in atrial fibrillation, syncope, and the clinical characteristics of heart disease, as well as various studies on familial heart disease and chronic ischemic heart disease. In geriatric cardiology, the most relevant studies published in 2014 involve heart failure, degenerative aortic stenosis, and data on atrial fibrillation in the geriatric population. In heart failure and transplantation, the most noteworthy developments concern the importance of multidisciplinary units and patients with preserved systolic function. Other notable publications were those related to iron deficiency, new drugs, and new devices and biomarkers. Finally, we review studies on acute heart failure and transplantation, such as inotropic drugs and ventricular assist devices. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Improving awareness, knowledge and heart-related lifestyle of coronary heart disease among working population through a mHealth programme: study protocol.

PubMed

Wang, Wenru; Zhang, Hui; Lopez, Violeta; Wu, Vivien Xi; Poo, Danny Chiang Choon; Kowitlawakul, Yanika

2015-09-01

To develop a mHealth programme, entitled 'Care4Heart' for the working population in Singapore and thereafter examine its feasibility and effectiveness in increasing the awareness and knowledge of coronary heart disease and improving their heart-related lifestyle. Teaching and encouraging the working population to adopt a healthier lifestyle could result in preventing and/or decreasing the incidence of coronary heart disease among this population. The use of mobile application (app) is the next logical wave of healthcare support tools to prevent and manage chronic diseases like coronary heart disease. A quasi-experimental longitudinal study design. The study will be conducted in a tertiary university in Singapore. A non-probability, quota sampling of 200 participants will be recruited including 100 academic and research staff, 50 administrative staff and 50 support staff and business owners. Once consent is obtained, the newly developed mobile app will be installed onto the participants' smartphones and a well-trained research assistant will brief the participant on the use of the app. The main outcomes will be measured using the survey questionnaires: Awareness of coronary heart disease, Heart Disease Fact Questionnaire-2, Behavioural Risk Factor Surveillance System and Perceived Stress Scale. Data will be collected at baseline and at the 4th week and 6th month thereafter. If this project is successful, Care4Heart - a mHealth and novel prevention educational programme for the working population in Singapore - can be used to promote knowledge and positive heart-related lifestyle changes to prevent coronary heart disease. © 2015 John Wiley & Sons Ltd.

Other Factors That Affect Heart Disease: Birth Control Pills

MedlinePlus

... Heart Handbook for Women Other Factors That Affect Heart Disease Birth Control Pills Studies show that women who ... t had any more complications because of my heart disease." — Diane Pay attention to diabetes. Levels of glucose, ...

Selection of reference genes for gene expression studies in heart failure for left and right ventricles.

PubMed

Li, Mengmeng; Rao, Man; Chen, Kai; Zhou, Jianye; Song, Jiangping

2017-07-15

Real-time quantitative reverse transcriptase-PCR (qRT-PCR) is a feasible tool for determining gene expression profiles, but the accuracy and reliability of the results depends on the stable expression of selected housekeeping genes in different samples. By far, researches on stable housekeeping genes in human heart failure samples are rare. Moreover the effect of heart failure on the expression of housekeeping genes in right and left ventricles is yet to be studied. Therefore we aim to provide stable housekeeping genes for both ventricles in heart failure and normal heart samples. In this study, we selected seven commonly used housekeeping genes as candidates. By using the qRT-PCR, the expression levels of ACTB, RAB7A, GAPDH, REEP5, RPL5, PSMB4 and VCP in eight heart failure and four normal heart samples were assessed. The stability of candidate housekeeping genes was evaluated by geNorm and Normfinder softwares. GAPDH showed the least variation in all heart samples. Results also indicated the difference of gene expression existed in heart failure left and right ventricles. GAPDH had the highest expression stability in both heart failure and normal heart samples. We also propose using different sets of housekeeping genes for left and right ventricles respectively. The combination of RPL5, GAPDH and PSMB4 is suitable for the right ventricle and the combination of GAPDH, REEP5 and RAB7A is suitable for the left ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

The year 2013 in the European Heart Journal--Cardiovascular Imaging: Part II.

PubMed

Plein, Sven; Edvardsen, Thor; Pierard, Luc A; Saraste, Antti; Knuuti, Juhani; Maurer, Gerald; Lancellotti, Patrizio

2014-08-01

The new multi-modality cardiovascular imaging journal, European Heart Journal - Cardiovascular Imaging, was created in 2012. Here we summarize the most important studies from the journal's second year in two articles. Part I of the review has summarized studies in myocardial function, myocardial ischaemia, and emerging techniques in cardiovascular imaging. Part II is focussed on valvular heart diseases, heart failure, cardiomyopathies, and congenital heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The year 2013 in the European Heart Journal--Cardiovascular Imaging. Part I.

PubMed

Edvardsen, Thor; Plein, Sven; Saraste, Antti; Pierard, Luc A; Knuuti, Juhani; Maurer, Gerald; Lancellotti, Patrizio

2014-07-01

The new multimodality cardiovascular imaging journal, European Heart Journal - Cardiovascular Imaging, was created in 2012. Here, we summarize the most important studies from the journal's second year in two articles. Part I of the review will focus on studies in myocardial function, myocardial ischaemia, and emerging techniques in cardiovascular imaging, and Part II will focus on valvular heart diseases, heart failure, cardiomyopathies, and congenital heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Heart rate and physical activity patterns in persons with profound intellectual and multiple disabilities.

PubMed

Waninge, Aly; van der Putten, Annette A J; Stewart, Roy E; Steenbergen, Bert; van Wijck, Ruud; van der Schans, Cees P

2013-11-01

Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity levels of persons with PIMD and to analyze these heart rate patterns according to participant characteristics, observed level of activity, days, and time of day. The heart rate patterns of 24 participants with PIMD were measured continuously using a heart rate monitor for 8 h · d for a period of 6 days. Physical activity levels were measured with questionnaires. Data were analyzed using multilevel analysis. The results indicate that the participants use only 32% of their heart rate reserve over 6 days. The intensity of heart rate reserve ranged from 1 to 62%. On a given day, wide ranges in heart rates between participants and within persons were observed. Between days, only small ranges in the heart rate were found. The participants could be grouped into 4 classes according to their heart rate. In addition, factors such as time of day, physical activity, and age are significantly related to heart rate patterns. In conclusion, this study is an important first step in exploring activity patterns based on heart rate patterns in persons with PIMD. The participants used relatively small fractions of their heart rate reserves. Time of day and age appear to have a considerable influence on heart rate patterns. The observed classes in heart rate patterns suggest that other probably more personal and psychosocial factors have significant influences on heart rate patterns, as well.

Fear and distress disorders as predictors of heart disease: a temporal perspective

PubMed Central

Roest, AM; de Jonge, P; Lim, C; Stein, DJ; Al-Hamzawi, A; Alonso, J; Benjet, C; Bruffaerts, R; Bunting, B; Caldas-de-Almeida, JM; Ciutan, M; de Girolamo, G; Hu, C; Levinson, D; Nakamura, Y; Navarro-Mateu, F; Piazza, M; Posada-Villa, J; Torres, Y; Wojtyniak, B; Kessler, RC; Scott, KM

2017-01-01

Objective Few studies have been able to contrast associations of anxiety and depression with heart disease. These disorders can be grouped in fear and distress disorders. Aim of this study was to study the association between fear and distress disorders with subsequent heart disease, taking into account the temporal order of disorders. Methods Twenty household surveys were conducted in 18 countries (n=53791; person years=2,212,430). The Composite International Diagnostic Interview assessed lifetime prevalence and age at onset of disorders, and respondents were categorized into categories based on the presence and timing of fear and distress disorders. Heart disease was indicated by self-report of physician-diagnosed heart disease or self-report of heart attack, together with year of onset. Survival analyses estimated associations between disorder categories and heart disease. Results Most respondents with fear or distress disorders had either pure distress or pure fear (8.5% and 7.7% of total sample), while fear preceded distress in the large majority of respondents with comorbid fear and distress (3.8% of total sample). Compared to the “no fear or distress disorder” category, respondents with pure fear disorder had the highest odds of subsequent heart disease (OR:1.8;95%CI:1.5–2.2; p<.001) and compared to respondents with pure distress disorder, these respondents were at a significantly increased risk of heart disease (OR:1.3;95%CI:1.0–1.6; p=0.020). Conclusion This novel analytic approach indicates that the risk of subsequent self-reported heart disease associated with pure fear disorder is significantly larger than the risk associated with distress disorder. These results should be confirmed in prospective studies using objective measures of heart disease. PMID:28545795

Fear and distress disorders as predictors of heart disease: A temporal perspective.

PubMed

Roest, A M; de Jonge, P; Lim, C W W; Stein, D J; Al-Hamzawi, A; Alonso, J; Benjet, C; Bruffaerts, R; Bunting, B; Caldas-de-Almeida, J M; Ciutan, M; de Girolamo, G; Hu, C; Levinson, D; Nakamura, Y; Navarro-Mateu, F; Piazza, M; Posada-Villa, J; Torres, Y; Wojtyniak, B; Kessler, R C; Scott, K M

2017-05-01

Few studies have been able to contrast associations of anxiety and depression with heart disease. These disorders can be grouped in fear and distress disorders. Aim of this study was to study the association between fear and distress disorders with subsequent heart disease, taking into account the temporal order of disorders. Twenty household surveys were conducted in 18 countries (n=53791; person years=2,212,430). The Composite International Diagnostic Interview assessed lifetime prevalence and age at onset of disorders, and respondents were categorized into categories based on the presence and timing of fear and distress disorders. Heart disease was indicated by self-report of physician-diagnosed heart disease or self-report of heart attack, together with year of onset. Survival analyses estimated associations between disorder categories and heart disease. Most respondents with fear or distress disorders had either pure distress or pure fear (8.5% and 7.7% of total sample), while fear preceded distress in the large majority of respondents with comorbid fear and distress (3.8% of total sample). Compared to the "no fear or distress disorder" category, respondents with pure fear disorder had the highest odds of subsequent heart disease (OR:1.8; 95%CI:1.5-2.2; p<0.001) and compared to respondents with pure distress disorder, these respondents were at a significantly increased risk of heart disease (OR:1.3; 95%CI:1.0-1.6; p=0.020). This novel analytic approach indicates that the risk of subsequent self-reported heart disease associated with pure fear disorder is significantly larger than the risk associated with distress disorder. These results should be confirmed in prospective studies using objective measures of heart disease. Copyright © 2017. Published by Elsevier Inc.

Genome-wide compendium and functional assessment of in vivo heart enhancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

DOE PAGES

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; ...

2016-10-05

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

PubMed Central

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; Fukuda-Yuzawa, Yoko; Osterwalder, Marco; Mannion, Brandon J.; May, Dalit; Spurrell, Cailyn H.; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Lee, Elizabeth; Garvin, Tyler H.; Kato, Momoe; Akiyama, Jennifer A.; Afzal, Veena; Lee, Ah Young; Gorkin, David U.; Ren, Bing; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2016-01-01

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function. PMID:27703156

Genome-wide association studies and resting heart rate.

PubMed

Kilpeläinen, Tuomas O

Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal variants and genes and gain further insights into the biological mechanisms underlying the observed associations. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of competition on heart rate during kart driving: A field study.

PubMed

Matsumura, Kenta; Yamakoshi, Takehiro; Yamakoshi, Yasuhiro; Rolfe, Peter

2011-09-09

Both the act of competing, which can create a kind of mental stress, and participation in motor sports, which induces physical stress from intense g-forces, are known to increase heart rate dramatically. However, little is known about the specific effect of competition on heart rate during motor sports, particularly during four-wheel car driving. The goal of this preliminary study, therefore, was to investigate whether competition increases heart rate under such situations. The participants drove an entry-level formula kart during two competitive races and during solo driving against the clock while heart rate and g-forces were measured. Analyses showed that heart rate values during the races (168.8 beats/min) were significantly higher than those during solo driving (140.9 beats/min) and rest (75.1 beats/min). The results of this preliminary study indicate that competition heightens heart rate during four-wheel car driving. Kart drivers should be concerned about maintaining good health and developing physical strength.

The effect of competition on heart rate during kart driving: A field study

PubMed Central

2011-01-01

Background Both the act of competing, which can create a kind of mental stress, and participation in motor sports, which induces physical stress from intense g-forces, are known to increase heart rate dramatically. However, little is known about the specific effect of competition on heart rate during motor sports, particularly during four-wheel car driving. The goal of this preliminary study, therefore, was to investigate whether competition increases heart rate under such situations. Findings The participants drove an entry-level formula kart during two competitive races and during solo driving against the clock while heart rate and g-forces were measured. Analyses showed that heart rate values during the races (168.8 beats/min) were significantly higher than those during solo driving (140.9 beats/min) and rest (75.1 beats/min). Conclusions The results of this preliminary study indicate that competition heightens heart rate during four-wheel car driving. Kart drivers should be concerned about maintaining good health and developing physical strength. PMID:21906298

Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project.

PubMed

Ahmad, Faraz S; Ning, Hongyan; Rich, Jonathan D; Yancy, Clyde W; Lloyd-Jones, Donald M; Wilkins, John T

2016-12-01

This study was designed to quantify the relationship between the absence of heart failure risk factors in middle age and incident heart failure, heart failure-free survival, and overall survival. Quantification of years lived free from heart failure in the context of risk factor burden in mid-life may improve risk communication and prevention efforts. We conducted a pooled, individual-level analysis sampling from communities across the United States as part of 4 cohort studies: the Framingham Heart, Framingham Offspring, Chicago Heart Association Detection Project in Industry, and ARIC (Atherosclerosis Risk In Communities) studies. Participants with and without hypertension (blood pressure ≥140/90 mm Hg or treatment), obesity (body mass index ≥30 kg/m 2 ), or diabetes (fasting glucose ≥126 mg/dl or treatment), and combinations of these factors, at index ages of 45 years and 55 years through 95 years. Competing risk-adjusted Cox models, a modified Kaplan-Meier estimator, and Irwin's restricted mean were used to estimate the association between the absence of risk factors at mid-life and incident heart failure, heart failure-free survival, and overall survival. For participants at age 45 years, over 516,537 person-years of follow-up, 1,677 incident heart failure events occurred. Men and women with no risk factors, compared to those with all 3, had 73% to 85% lower risks of incident heart failure. Men and women without hypertension, obesity, or diabetes at age 45 years lived on average 34.7 years and 38.0 years without incident heart failure, and they lived on average an additional 3 years to 15 years longer free of heart failure than those with 1, 2, or 3 risk factors. Similar trends were seen when stratified by race and at index age 55 years. Prevention of hypertension, obesity, and diabetes by ages 45 years and 55 years may substantially prolong heart failure-free survival, decrease heart failure-related morbidity, and reduce the public health impact of heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Changes in Heart Rate Associated with Exenatide Once Weekly: Pooled Analysis of Clinical Data in Patients with Type 2 Diabetes.

PubMed

Marso, Steven P; Hardy, Elise; Han, Jenny; Wang, Hui; Chilton, Robert J

2018-04-01

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and - 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = - 0.3 to - 0.4). Baseline heart rate was the strongest predictor of increased heart rate. Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.

Inpatient Utilization and Costs for Medicare Fee-for-Service Beneficiaries with Heart Failure

PubMed Central

Fitch, Kathryn; Pelizzari, Pamela M.; Pyenson, Bruce

2016-01-01

Background Although the medical and economic burden of heart failure in the United States is already substantial, it will likely grow as the population ages and life expectancy increases. Not surprisingly, most of the heart failure burden is borne by individuals aged ≥65 years, many of whom are in the Medicare population. The population-based utilization and costs of inpatient care for Medicare beneficiaries with heart failure are not well understood by payers and providers. Objective To create a real-world view of utilization and costs associated with inpatient admissions, readmissions, and admissions to skilled nursing facilities among Medicare fee-for-service (FFS) beneficiaries with heart failure. Methods The study used the 2011 and 2012 Medicare 5% sample limited data set to perform a retrospective analysis of claims data. The look-back year that was used to identify certain patient characteristics was 2011, and 2012 was the analysis period for the study. Beneficiaries with heart failure were defined as those who had ≥1 acute inpatient, emergency department, nonacute inpatient, or outpatient claims in 2012 containing an International Classification of Diseases, Ninth Revision code for heart failure. To be included in the study, beneficiaries with heart failure had to have eligibility for ≥1 months in 2012 and in all 2011 months, with Part A and Part B eligibility in all the study months, and no enrollment in an HMO (Medicare Advantage plan). Utilization of inpatient admissions, inpatient readmissions, and skilled nursing facility admissions in 2012 were reported for Medicare FFS beneficiaries with heart failure and for all Medicare FFS beneficiaries. The costs for key metrics included all allowed Medicare payments in 2012 US dollars. Results The 2012 Medicare FFS population for this study consisted of 1,461,935 patients (1,301,545 without heart failure; 160,390 with heart failure); the heart failure prevalence was 11%. The Medicare-allowed cost per member per month (PMPM) was $3395 for a patient with heart failure, whereas the allowed cost for the total Medicare population was $1045 PMPM. The Medicare–allowed amounts for the population with heart failure accounted for 34% of the total annual Medicare FFS population–allowed amounts. The heart failure population constituted 41.5%, 55.3%, and 49.5% of total Medicare FFS inpatient admissions, readmissions, and admissions to skilled nursing facilities, respectively. The costs of inpatient admissions, readmissions, and admissions to skilled nursing facilities among the heart failure population contributed $182 PMPM (17.5%), $58 PMPM (5.6%), and $46 PMPM (4.4%), respectively, to the total Medicare FFS population–allowed cost of $1045 PMPM. Conclusions Medicare FFS beneficiaries with heart failure have high inpatient admission and readmission rates and generate substantial costs. Because a substantial portion of all inpatient admissions are for Medicare beneficiaries with heart failure, it is reasonable for hospitals in Medicare accountable care organizations to focus on more aggressive post–acute care management, including a focus on reducing readmissions for the population with heart failure. Our study findings highlight areas of high service utilization and cost for Medicare patients with heart failure that can be of value to Medicare, Medicare Advantage plans, and providers. PMID:27182428

Service Coordination Policies and Models: National Status.

ERIC Educational Resources Information Center

Harbin, Gloria L.; Bruder, M.; Mazzarella, C.; Gabbard, G.; Reynolds, C.

This report discusses the findings of a study that investigated state coordination of early intervention services for infants, toddlers, and young children with disabilities. State Part C coordinators participated in a survey that sought their perceptions of values under girding service coordination, approach to service coordination, policies,…

Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans.

PubMed

Sharifi-Sanjani, Maryam; Oyster, Nicholas M; Tichy, Elisia D; Bedi, Kenneth C; Harel, Ofer; Margulies, Kenneth B; Mourkioti, Foteini

2017-09-07

Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution. In this study, total of 63 human left ventricular samples, including 37 diseased and 26 nonfailing donor hearts, were stained for telomeres in combination with cardiomyocyte- or α-smooth muscle cell-specific markers, cardiac troponin T, and smooth muscle actin, respectively, and assessed for telomere length. Patients with heart failure demonstrate shorter cardiomyocyte telomeres compared with nonfailing donors, which is specific only to cardiomyocytes within diseased human hearts and is associated with cardiomyocyte DNA damage. Our data further reveal that hypertrophic hearts with reduced ejection fraction exhibit the shortest telomeres. In contrast to other reported cell types, no difference in cardiomyocyte telomere length is evident with age. However, under the disease state, telomere attrition manifests in both young and older patients with cardiac hypertrophy. Finally, we demonstrate that cardiomyocyte-telomere length is better sustained in women than men under diseased conditions. This study provides the first evidence of cardiomyocyte-specific telomere shortening in heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

PubMed Central

ALLEN, LARRY A.; FELKER, G. MICHAEL; MEHRA, MANDEEP R.; CHIONG, JUN R.; DUNLAP, STEPHANIE H.; GHALI, JALAL K.; LENIHAN, DANIEL J.; OREN, RON M.; WAGONER, LYNNE E.; SCHWARTZ, TODD A.; ADAMS, KIRKWOOD F.

2014-01-01

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. PMID:20206898

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.

PubMed

Allen, Larry A; Felker, G Michael; Mehra, Mandeep R; Chiong, Jun R; Dunlap, Stephanie H; Ghali, Jalal K; Lenihan, Daniel J; Oren, Ron M; Wagoner, Lynne E; Schwartz, Todd A; Adams, Kirkwood F

2010-03-01

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Women's perceptions of heart disease and breast cancer and the association with media representations of the diseases

PubMed Central

Berry, Tanya R.; Stearns, Jodie A.; Courneya, Kerry S.; McGannon, Kerry R.; Norris, Colleen M.; Rodgers, Wendy M.; Spence, John C.

2016-01-01

Abstract Background This research examined differences in perceptions of heart disease compared with breast cancer and if the differences are reflected in media presentations of the diseases. Relationships of differences in perceptions to demographic groups, heart disease risk factors and health behaviors were examined. Methods Study 1 was a quantitative content analysis of articles and advertisements related to heart disease or breast cancer. Results There were greater perceptions of susceptibility, preventability and controllability of heart disease and lower perceptions regarding seriousness, fearfulness and extent to which family history determines disease development of heart disease compared with breast cancer. Five times more pieces related to breast cancer were found compared with heart disease. Study 2 was a survey of 1524 women. More articles and advertisements about breast cancer than heart disease were found, and survey participants reported seeing significantly more breast cancer than heart disease media. Younger women had greater perceived susceptibility of breast cancer relative to heart disease while the content analysis revealed that the heart disease pieces were more likely to feature women older than 40 years of age. Conclusions This research is an important step in the development of theories regarding causal effects of media on health perceptions and behaviors. PMID:28158680

2013 update on congenital heart disease, clinical cardiology, heart failure, and heart transplant.

PubMed

Subirana, M Teresa; Barón-Esquivias, Gonzalo; Manito, Nicolás; Oliver, José M; Ripoll, Tomás; Lambert, Jose Luis; Zunzunegui, José L; Bover, Ramon; García-Pinilla, José Manuel

2014-03-01

This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The integration of an online module on student learning.

PubMed

Yehle, Karen S; Chang, Karen

2012-11-01

Heart failure is a prevalent and costly condition. Patients with better self-management are less likely to be rehospitalized. An online interactive heart failure module was developed and integrated into a medical-surgical nursing course to assist students in learning how to care for patients with heart failure. The purpose of this study was to examine whether the integration of an online heart failure module improved baccalaureate nursing students' heart failure self-management knowledge. A pretest/posttest design was used to examine the effects of student knowledge of heart failure self-management following implementation of an online module. Among 235 students, significant improvement of heart failure self-management knowledge was observed (P < .05). The mean posttest scores ranged from 13.82 to 15.93. Students had problems mastering knowledge of weight monitoring, use of nonsteroidal anti-inflammatory drugs, symptoms to report to physicians, and potassium-based salt substitutes. These findings were similar to four studies examining nurses' knowledge of heart failure. Students and nurses have difficulty mastering similar heart failure education concepts. An additional strategy, such as simulated or case scenarios, needs to be developed to help nurses and nursing students master all key concepts of heart failure self-management.

Health Representations, Perceived Valence, and Concept Associations for Symbols as Food Cues: A Mixed-Methods Approach.

PubMed

Thomas, Erica L; Puig Ribera, Anna; Senye-Mir, Anna; Eves, Frank F

2016-11-01

Researchers have experimented with a range of point-of-purchase (PoP) interventions in supermarkets, restaurants, and cafeterias. In general, these interventions have employed written materials. This research tested symbols to visually summarize information about the (un)healthiness of food. Study one explored health representations and valence associated with the image of a heart, a bathroom scale, and a running shoe using qualitative field interviews (N = 1200). Study two explored accessibility of a priori concept associations for two of those images, stratified by valence, in a computerized response latency task (N = 40). Study one indicted that the heart was best linked to its intended theme "heart health." Concerning valence, the heart was seen as both positive and negative whereas the scale was less likely to be viewed as positive relative to the running shoe. In study two, the heart was linked to five of the six a priori concepts and there was evidence that three of these were more accessible. Overall, the heart was better linked to positive poles than negative ones. A heart symbol may be useful to prompt heart healthy choices at the PoP. There was evidence that a scale may bias choice away from undesirable foods.

Multiple Coordination Patterns in Infant and Adult Vocalizations

PubMed Central

Abney, Drew H.; Warlaumont, Anne S.; Oller, D. Kimbrough; Wallot, Sebastian; Kello, Christopher T.

2017-01-01

The study of vocal coordination between infants and adults has led to important insights into the development of social, cognitive, emotional and linguistic abilities. We used an automatic system to identify vocalizations produced by infants and adults over the course of the day for fifteen infants studied longitudinally during the first two years of life. We measured three different types of vocal coordination: coincidence-based, rate-based, and cluster-based. Coincidence-based and rate-based coordination are established measures in the developmental literature. Cluster-based coordination is new and measures the strength of matching in the degree to which vocalization events occur in hierarchically nested clusters. We investigated whether various coordination patterns differ as a function of vocalization type, whether different coordination patterns provide unique information about the dynamics of vocal interaction, and how the various coordination patterns each relate to infant age. All vocal coordination patterns displayed greater coordination for infant speech-related vocalizations, adults adapted the hierarchical clustering of their vocalizations to match that of infants, and each of the three coordination patterns had unique associations with infant age. Altogether, our results indicate that vocal coordination between infants and adults is multifaceted, suggesting a complex relationship between vocal coordination and the development of vocal communication. PMID:29375276

Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.

PubMed

Avella, Joseph; Kunaparaju, Naveen; Kumar, Sunil; Lehrer, Michael; Zito, S William; Barletta, Michael

2010-09-01

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if DFE is abused chronically due to continued uptake into lowly perfused tissues with repeated dosing.

HSF1 deficiency accelerates the transition from pressure overload-induced cardiac hypertrophy to heart failure through endothelial miR-195a-3p-mediated impairment of cardiac angiogenesis.

PubMed

Wang, Shijun; Wu, Jian; You, Jieyun; Shi, Hongyu; Xue, Xiaoyu; Huang, Jiayuan; Xu, Lei; Jiang, Guoliang; Yuan, Lingyan; Gong, Xue; Luo, Haiyan; Ge, Junbo; Cui, Zhaoqiang; Zou, Yunzeng

2018-05-01

Heat shock transcription factor 1 (HSF1) deficiency aggravates cardiac remodeling under pressure overload. However, the mechanism is still unknown. Here we employed microRNA array analysis of the heart tissue of HSF1-knockout (KO) mice to investigate the potential roles of microRNAs in pressure overload-induced cardiac remodeling under HSF-1 deficiency, and the profiles of 478 microRNAs expressed in the heart tissues of adult HSF1-KO mice were determined. We found that the expression of 5 microRNAs was over 2-fold higher expressed in heart tissues of HSF1-KO mice than in those of wild-type (WT) control mice. Of the overexpressed microRNAs, miR-195a-3p had the highest expression level in HSF1-null endothelial cells (ECs). Induction with miR-195a-3p in ECs significantly suppressed CD31 and VEGF, promoted AngII-induced EC apoptosis, and impaired capillary-like tube formation. In vivo, the upregulation of miR-195a-3p accentuated cardiac hypertrophy, increased the expression of β-MHC and ANP, and compromised systolic function in mice under pressure overload induced by transverse aortic constriction (TAC). By contrast, antagonism of miR-195a-3p had the opposite effect on HSF1-KO mice. Further experiments confirmed that AMPKα2 was the direct target of miR-195a-3p. AMPKα2 overexpression rescued the reduction of eNOS and VEGF, and the impairment of angiogenesis that was induced by miR-195a-3p. In addition, upregulation of AMPKα2 in the myocardium of HSF1-null mice by adenovirus-mediated gene delivery enhanced CD31, eNOS and VEGF, reduced β-MHC and ANP, alleviated pressure overload-mediated cardiac hypertrophy and restored cardiac function. Our findings revealed that the upregulation of miR-195a-3p due to HSF1 deficiency impaired cardiac angiogenesis by regulating AMPKα2/VEGF signaling, which disrupted the coordination between the myocardial blood supply and the adaptive hypertrophic response and accelerated the transition from cardiac hypertrophy to heart failure in response to pressure overload. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protease Activated Receptor-2 Contributes to Heart Failure

PubMed Central

Antoniak, Silvio; Sparkenbaugh, Erica M.; Tencati, Michael; Rojas, Mauricio; Mackman, Nigel; Pawlinski, Rafal

2013-01-01

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. PMID:24312345

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

PubMed

Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C

2014-08-01

Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.

[Effectiveness of heart tumor therapy in the cardiology department during 7 year follow-up].

PubMed

Dabek, Józefa; Twardowski, Romuald; Jakubowski, Daniel; Michniak, Barbara; Swiderski, Robert; Gasior, Zbigniew

2009-11-01

Neoplasms of the heart are rare. Usually asymptomatic on the early stage are diagnosed incidentally. Among primary heart neoplasms the most often benign tumors are diagnosed--mostly myxomas, whereas the majority of malignant heart tumors are sarcomas. The aim of this paper was to present heart tumors diagnosed in the cardiology department, their symptoms, used diagnostic tests and therapy and to show after therapy quality of life changes. There were 18 patients included to the study, whom during hospitalization in the cardiology department heart tumors were diagnosed. There were 11 women and 7 men, aged from 33- to 76-years-old (mean 60,5 years). To all of the patients medical interview, physical examination, EKG, UCG and laboratory test were performed. Additionally in some cases computed tomography or magnetic resonance imaging of the chest and coronary angiograms were done. Based on the diagnostic tests results the patients were qualified to conservative or surgical treatment. Among 18 heart tumor patients in 12 cases primary benign tumors were diagnosed (66,6%), 1 patient had primary malignant tumor (5,5%), there were 3 cases of metastatic tumors (16,6%) and 2 patients with non-neoplasmic tumors--clots (11,1%). From 18 subjects with heart tumor 3 patients died because of advanced stage of neoplasmic disease and presence of metastatic tumors in the heart. Results of the study show, that heart tumors, regardless of development of diagnostic tests, are still diagnosed too late. The study group follow-up proved, that early diagnosis and proper heart tumor treatment prevented complications and improved the quality of life. It is worth to emphasize, that coronary angiogram in some cases allowed to diagnose coronary artery disease, to treat heart tumor and to perform coronary artery by-pass grafting simultaneously.

Cardiac strain findings in children with latent rheumatic heart disease detected by echocardiographic screening.

PubMed

Beaton, Andrea; Richards, Hedda; Ploutz, Michelle; Gaur, Lasya; Aliku, Twalib; Lwabi, Peter; Ensing, Greg; Sable, Craig

2017-08-01

Identification of patients with latent rheumatic heart disease by echocardiography presents a unique opportunity to prevent disease progression. Myocardial strain is a more sensitive indicator of cardiac performance than traditional measures of systolic function. The objective of this study was to test the hypothesis that abnormalities in myocardial strain may be present in children with latent rheumatic heart disease. Standard echocardiography images with electrocardiogram gating were obtained from Ugandan children found to have latent rheumatic heart disease as well as control subjects. Traditional echocardiography measures of systolic function were obtained, and offline global longitudinal strain analysis was performed. Comparison between groups was performed using strain as a continuous (Mann-Whitney U-test) and categorical (cut-off 5th percentile for age) variable. Our study included 14 subjects with definite rheumatic heart disease, 13 with borderline rheumatic heart disease, and 112 control subjects. None of the subjects had abnormal left ventricular size or ejection fraction. Global longitudinal strain was lower than the 5th percentile in 44% of the subjects with any rheumatic heart disease (p=0.002 versus controls) and 57% of the subjects with definite rheumatic heart disease (p=0.03). The mean absolute strain values were significantly lower when comparing subjects with any rheumatic heart disease with controls (20.4±3.95 versus 22.4±4.35, p=0.025) and subjects with definite rheumatic heart disease with controls (19.9±4.25 versus 22.4±4.35, p=0.033). Global longitudinal strain is decreased in subjects with rheumatic heart disease in the absence of abnormal systolic function. Larger studies with longer-term follow-up are required to determine whether there is a role for strain to help better understand the pathophysiology of latent rheumatic heart disease.

[Quality indicators for National Disease Management Guidelines using the example of the National Disease Management Guideline for "Chronic Heart Failure"].

PubMed

Nothacker, Monika Judith; Langer, Thomas; Weinbrenner, Susanne

2011-01-01

Together with an expert committee a structured approach to determining quality indicators for National Disease Management Guidelines has been developed. The key steps of this approach include: introducing guideline authors to the methodology at an early stage of the process of guideline development, pre-selecting recommendations of the guideline which are potentially measurable by means of quality indicators, assessing the potentially measurable quality indicators in written form using five criteria (including their importance for the health care system and clarity of definitions) and approving them in a formal consensus process. For lack of a database these quality indicators must be regarded as preliminary. For the National Disease Management Guideline "Chronic Heart Failure" nine rate-based indicators have been chosen. The indicators correspond to important strong recommendations (grade of recommendation: A) from the fields of diagnosis (two), general therapeutic strategy (two), specific treatment (three), clinical monitoring (one) and co-ordination of care (one). In a second step, the quality indicators have to be validated within a pilot project. The determination and assessment of the potential quality indicators have revealed room for improvement of guideline development. In particular, there is a need for more health care data and for specification of recommendations.

[Results of Monitoring of the Plan of Measures Directed to Reduction of Ischemic Heart Disease in North Caucasus Republics. Analysis of Dynamics of Cardio-Vascular Mortality].

PubMed

Mamedov, M N

2016-05-01

Comparative analysis of dynamics of cardiovascular mortality in Russia and foreign countries as well as main directions of development of cardiological service in Russia are presented in this review article. Plan of measures for reduction of mortality from ischemic heart disease (IHD) was created in 2015. This plan comprises 4 blocks of assessment of the following measures: directed at improvement of primary IHD prevention (1), directed at secondary prevention of complications of IHD (2); directed at improvement of efficacy of medical care of patients with IHD (3), and directed at monitoring of some demographic parameters (4). The article also contains results of monitoring of realization of the plan of IHD reduction in republics of North Caucasus. Realization of the program on healthy life style (HLS) lacks coordination between ministries. Mass information media are not sufficiently involved in propaganda of HLS. Mean achievement of target levels of main risk factors does not exceed 30-35%. First stage of prophylactic medical examination (dispanserization) has been fulfilled in 65%. High technology care is available both in federal and regional centers. Organization of effective urgent medical service, drug supply, and rehabilitation of patients with IHD are important aspects of improvement of secondary prevention in the region.

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation.

PubMed

Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

2018-03-01

Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N ω -nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

Patient-Specific Modeling of Intraventricular Hemodynamics

NASA Astrophysics Data System (ADS)

Vedula, Vijay; Marsden, Alison

2017-11-01

Heart disease is the one of the leading causes of death in the world. Apart from malfunctions in electrophysiology and myocardial mechanics, abnormal hemodynamics is a major factor attributed to heart disease across all ages. Computer simulations offer an efficient means to accurately reproduce in vivo flow conditions and also make predictions of post-operative outcomes and disease progression. We present an experimentally validated computational framework for performing patient-specific modeling of intraventricular hemodynamics. Our modeling framework employs the SimVascular open source software to build an anatomic model and employs robust image registration methods to extract ventricular motion from the image data. We then employ a stabilized finite element solver to simulate blood flow in the ventricles, solving the Navier-Stokes equations in arbitrary Lagrangian-Eulerian (ALE) coordinates by prescribing the wall motion extracted during registration. We model the fluid-structure interaction effects of the cardiac valves using an immersed boundary method and discuss the potential application of this methodology in single ventricle physiology and trans-catheter aortic valve replacement (TAVR). This research is supported in part by the Stanford Child Health Research Institute and the Stanford NIH-NCATS-CTSA through Grant UL1 TR001085 and partly through NIH NHLBI R01 Grant 5R01HL129727-02.

Cardiovascular disease prevention and lifestyle interventions: effectiveness and efficacy.

PubMed

Haskell, William L

2003-01-01

Over the past half century scientific data support the strong relationship between the way a person or population lives and their risk for developing or dying from cardiovascular disease (CVD). While heredity can be a major factor for some people, their personal health habits and environmental/cultural exposure are more important factors. CVD is a multifactor process that is contributed to by a variety of biological and behavioral characteristics of the person including a number of well-established and emerging risk factors. Not smoking, being physically active, eating a heart healthy diet, staying reasonably lean, and avoiding major stress and depression are the major components of an effective CVD prevention program. For people at high risk of CVD, medications frequently need to be added to a healthy lifestyle to minimize their risk of a heart attack or stroke, particularly in persons with conditions such as hypertension, hypercholesterolemia, or hyperglycemia. Maintaining an effective CVD prevention program in technologically advanced societies cannot be achieved by many high-risk persons without effective and sustained support from a well-organized health care system. Nurse-provided or nurse-coordinated care management programs using an integrated or multifactor approach have been highly effective in reducing CVD morbidity and mortality of high-risk persons.

Characterization of myocardial lesions associated with cardiomyopathy syndrome in Atlantic salmon, Salmo salar L., using laser capture microdissection.

PubMed

Wiik-Nielsen, J; Løvoll, M; Fritsvold, C; Kristoffersen, A B; Haugland, Ø; Hordvik, I; Aamelfot, M; Jirillo, E; Koppang, E O; Grove, S

2012-12-01

Cardiomyopathy syndrome (CMS) in Atlantic salmon, Salmo salar L., is characterized by focal infiltration in the spongy myocardium and endocardium of the heart. The origin of the mononuclear infiltrate is unknown. Using experimentally infected fish, we investigated localization of the causative agent, piscine myocarditis virus (PMCV), within the heart and characterized the cell population associated with myocardial lesions. Cellular and transcriptional characteristics in the lesions were compared with adjacent non-infiltrated tissues using laser capture microdissection, RT-qPCR and immunohistochemistry. Our results reveal that PMCV is almost exclusively present in myocardial lesions. The inflammatory infiltrate comprises a variety of leucocyte populations, including T cells, B cells, MHC class II(+) and CD83(+) cells, most likely of the macrophage line. Correlation analyses demonstrated co-ordinated leucocyte activity at the site of the virus infection. Cellular proliferation and/or DNA repair was demonstrated within the myocardial lesions. Different cell populations, mainly myocytes, stained positive for proliferating cell nuclear antigen (PCNA). Densities of endothelial cells and fibroblasts were not significantly increased. The simultaneous presence of PMCV and various inflammatory cells in all myocardial lesions analysed may indicate that both viral lytic and immunopathological effects may contribute to the pathogenesis of CMS. © 2012 Blackwell Publishing Ltd.

Ultrasound based mitral valve annulus tracking for off-pump beating heart mitral valve repair

NASA Astrophysics Data System (ADS)

Li, Feng P.; Rajchl, Martin; Moore, John; Peters, Terry M.

2014-03-01

Mitral regurgitation (MR) occurs when the mitral valve cannot close properly during systole. The NeoChordtool aims to repair MR by implanting artificial chordae tendineae on flail leaflets inside the beating heart, without a cardiopulmonary bypass. Image guidance is crucial for such a procedure due to the lack of direct vision of the targets or instruments. While this procedure is currently guided solely by transesophageal echocardiography (TEE), our previous work has demonstrated that guidance safety and efficiency can be significantly improved by employing augmented virtuality to provide virtual presentation of mitral valve annulus (MVA) and tools integrated with real time ultrasound image data. However, real-time mitral annulus tracking remains a challenge. In this paper, we describe an image-based approach to rapidly track MVA points on 2D/biplane TEE images. This approach is composed of two components: an image-based phasing component identifying images at optimal cardiac phases for tracking, and a registration component updating the coordinates of MVA points. Preliminary validation has been performed on porcine data with an average difference between manually and automatically identified MVA points of 2.5mm. Using a parallelized implementation, this approach is able to track the mitral valve at up to 10 images per second.

Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

PubMed

Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

2016-08-01

Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

The real-world problem of care coordination: a longitudinal qualitative study with patients living with advanced progressive illness and their unpaid caregivers.

PubMed

Daveson, Barbara A; Harding, Richard; Shipman, Cathy; Mason, Bruce L; Epiphaniou, Eleni; Higginson, Irene J; Ellis-Smith, Clare; Henson, Lesley; Munday, Dan; Nanton, Veronica; Dale, Jeremy R; Boyd, Kirsty; Worth, Allison; Barclay, Stephen; Donaldson, Anne; Murray, Scott

2014-01-01

To develop a model of care coordination for patients living with advanced progressive illness and their unpaid caregivers, and to understand their perspective regarding care coordination. A prospective longitudinal, multi-perspective qualitative study involving a case-study approach. Serial in-depth interviews were conducted, transcribed verbatim and then analyzed through open and axial coding in order to construct categories for three cases (sites). This was followed by continued thematic analysis to identify underlying conceptual coherence across all cases in order to produce one coherent care coordination model. Fifty-six purposively sampled patients and 27 case-linked unpaid caregivers. Three cases from contrasting primary, secondary and tertiary settings within Britain. Coordination is a deliberate cross-cutting action that involves high-quality, caring and well-informed staff, patients and unpaid caregivers who must work in partnership together across health and social care settings. For coordination to occur, it must be adequately resourced with efficient systems and services that communicate. Patients and unpaid caregivers contribute substantially to the coordination of their care, which is sometimes volunteered at a personal cost to them. Coordination is facilitated through flexible and patient-centered care, characterized by accurate and timely information communicated in a way that considers patients' and caregivers' needs, preferences, circumstances and abilities. Within the midst of advanced progressive illness, coordination is a shared and complex intervention involving relational, structural and information components. Our study is one of the first to extensively examine patients' and caregivers' views about coordination, thus aiding conceptual fidelity. These findings can be used to help avoid oversimplifying a real-world problem, such as care coordination. Avoiding oversimplification can help with the development, evaluation and implementation of real-world coordination interventions for patients and their unpaid caregivers in the future.

Is depressed myocyte contractility centrally involved in heart failure?

PubMed

Houser, Steven R; Margulies, Kenneth B

2003-03-07

This review examines the evidence for and against the hypothesis that abnormalities in cardiac contractility initiate the heart failure syndrome and drive its progression. There is substantial evidence that the contractility of failing human hearts is depressed and that abnormalities of basal Ca2+ regulation and adrenergic regulation of Ca2+ signaling are responsible. The cellular and molecular defects that cause depressed myocyte contractility are not well established but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage, and release. There are also strong links between Ca2+ regulation, Ca2+ signaling pathways, hypertrophy, and heart failure that need to be more clearly delineated. There is not substantial direct evidence for a causative role for depressed contractility in the initiation and progression of human heart failure, and some studies show that heart failure can occur without depressed myocyte contractility. Stronger support for a causal role for depressed contractility in the initiation of heart failure comes from animal studies where maintaining or improving contractility can prevent heart failure. Recent clinical studies in humans also support the idea that beneficial heart failure treatments, such as beta-adrenergic antagonists, involve improved contractility. Current or previously used heart failure treatments that increase contractility, primarily by increasing cAMP, have generally increased mortality. Novel heart failure therapies that increase or maintain contractility or adrenergic signaling by selectively modulating specific molecules have produced promising results in animal experiments. How to reliably implement these potentially beneficial inotropic therapies in humans without introducing negative side effects is the major unanswered question in this field.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us.

PubMed

Fung, Erik; Hui, Elsie; Yang, Xiaobo; Lui, Leong T; Cheng, King F; Li, Qi; Fan, Yiting; Sahota, Daljit S; Ma, Bosco H M; Lee, Jenny S W; Lee, Alex P W; Woo, Jean

2018-01-01

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.

Heart rates increase after hatching in two species of natricine snakes

PubMed Central

Aubret, Fabien

2013-01-01

Experimental studies have shown heart rates to decrease from embryo to hatchling stage in turtles, remain steady in skinks, and increase in birds. However, no snake species has been studied in this regard. I recorded heart rate evolution trajectories from embryo to juvenile stage in 78 eggs from two species of European Natricine snakes. Unexpectedly, snakes behaved more like birds than turtles or lizards: heart rates increased after hatching in both N. maura and N. natrix, respectively by 43.92 ± 22.84% and 35.92 ± 24.52%. Heart rate shift was not related to an abrupt elevation of metabolism per se (snakes that increased their heart rates the most sharply grew the least after birth), but rather due to a number of smaller eggs that experienced lower than normal heart rates throughout the incubation and recovered a normal heart rate post-birth. This finding is discussed in the light of hatching synchrony benefits. PMID:24287712

Human Embryonic Stem Cell-Derived Cardiomyocytes Self-Arrange with Areas of Different Subtypes During Differentiation.

PubMed

Vestergaard, Maj Linea; Grubb, Søren; Koefoed, Karen; Anderson-Jenkins, Zoe; Grunnet-Lauridsen, Kristina; Calloe, Kirstine; Clausen, Christian; Christensen, Søren Tvorup; Møllgård, Kjeld; Andersen, Claus Yding

2017-11-01

The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESCs) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of hESC-derived cardiomyocytes (hESC-CMs) and examined how the expression levels of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2.5. Sharp electrode recordings to determine action potentials (APs) further revealed spatial organization of intracluster CM subtypes (ie, complex clusters). Nodal-, atrial-, and ventricular-like AP morphologies were detected within distinct regions of complex clusters. The ability of different CM subtypes to self-organize was documented by immunohistochemical analyses and a differential spatial expression of β-III tubulin, myosin light chain 2v (MLC-2V), and α-smooth muscle actin (α-SMA). Furthermore, all hESC-CM subtypes formed expressed primary cilia, which are known to coordinate cellular signaling pathways during cardiomyogenesis and heart development. This study expands the foundation for studying regulatory pathways for spatial and temporal CM differentiation during human cardiogenesis.

Improving interprofessional coordination in Dutch midwifery and obstetrics: a qualitative study

PubMed Central

2014-01-01

Background Coordination between the autonomous professional groups in midwifery and obstetrics is a key debate in the Netherlands. At the same time, it remains unclear what the current coordination challenges are. Methods To examine coordination challenges that might present a barrier to delivering optimal care, we conducted a qualitative field study focusing on midwifery and obstetric professional’s perception of coordination and on their routines. We undertook 40 interviews with 13 community midwives, 8 hospital-based midwives and 19 obstetricians (including two resident obstetricians), and conducted non-participatory observations at the worksite of these professional groups. Results We identified challenges in terms of fragmented organizational structures, different perspectives on antenatal health and inadequate interprofessional communication. These challenges limited professionals' coordinating capacity and thereby decreased their ability to provide optimal care. We also found that pregnant women needed to compensate for suboptimal coordination between community midwives and secondary caregivers by taking on an active role in facilitating communication between these professionals. Conclusions The communicative role that pregnant women play within coordination processes underlines the urgency to improve coordination. We recommend increasing multidisciplinary meetings and training, revising the financial reimbursement system, implementing a shared maternity notes system and decreasing the expertise gap between providers and clients. In the literature, communication by clients in support of coordination has been largely ignored. We suggest that studies include client communication as part of the coordination process. PMID:24731478

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI.

PubMed

Zhang, Lei; Allen, John; Hu, Lingzhi; Caruthers, Shelton D; Wickline, Samuel A; Chen, Junjie

2013-01-15

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (α(h)). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial α(h) decreased by ~30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function.

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI

PubMed Central

Zhang, Lei; Allen, John; Hu, Lingzhi; Caruthers, Shelton D.; Wickline, Samuel A.

2013-01-01

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (αh). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial αh decreased by ∼30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function. PMID:23161881

Characterizing Heart Failure in the Ventricular Volume Domain

PubMed Central

Kerkhof, Peter LM

2015-01-01

Heart failure (HF) may be accompanied by considerable alterations of left ventricular (LV) volume, depending on the particular phenotype. Two major types of HF have been identified, although heterogeneity within each category may be considerable. All variants of HF show substantially elevated LV filling pressures, which tend to induce changes in LV size and shape. Yet, one type of HF is characterized by near-normal values for LV end-diastolic volume (EDV) and even a smaller end-systolic volume (ESV) than in matched groups of persons without cardiac disease. Furthermore, accumulating evidence indicates that, both in terms of shape and size, in men and women, the heart reacts differently to adaptive stimuli as well as to certain pharmacological interventions. Adjustments of ESV and EDV such as in HF patients are associated with (reverse) remodeling mechanisms. Therefore, it is logical to analyze HF subtypes in a graphical representation that relates ESV to EDV. Following this route, one may expect that the two major phenotypes of HF are identified as distinct entities localized in different areas of the LV volume domain. The precise coordinates of this position imply unique characteristics in terms of the actual operating point for LV volume regulation. Evidently, ejection fraction (EF; equal to 1 minus the ratio of ESV and EDV) carries little information within the LV volume representation. Thus far, classification of HF is based on information regarding EF combined with EDV. Our analysis shows that ESV in the two HF groups follows different patterns in dependency of EDV. This observation suggests that a superior HF classification system should primarily be founded on information embodied by ESV. PMID:25780344

Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart.

PubMed

Tuncay, Erkan; Bitirim, Verda C; Durak, Aysegul; Carrat, Gaelle R J; Taylor, Kathryn M; Rutter, Guy A; Turan, Belma

2017-05-01

Changes in cellular free Zn 2+ concentration, including those in the sarco(endo)plasmic reticulum [S(E)R], are primarily coordinated by Zn 2+ transporters (ZnTs) whose identity and role in the heart are not well established. We hypothesized that ZIP7 and ZnT7 transport Zn 2+ in opposing directions across the S(E)R membrane in cardiomyocytes and that changes in their activity play an important role in the development of ER stress during hyperglycemia. The subcellular S(E)R localization of ZIP7 and ZnT7 was determined in cardiomyocytes and in isolated S(E)R preparations. Markedly increased mRNA and protein levels of ZIP7 were observed in ventricular cardiomyocytes from diabetic rats or high-glucose-treated H9c2 cells while ZnT7 expression was low. In addition, we observed increased ZIP7 phosphorylation in response to high glucose in vivo and in vitro. By using recombinant-targeted Förster resonance energy transfer sensors, we show that hyperglycemia induces a marked redistribution of cellular free Zn 2+ , increasing cytosolic free Zn 2+ and lowering free Zn 2+ in the S(E)R. These changes involve alterations in ZIP7 phosphorylation and were suppressed by small interfering RNA-mediated silencing of CK2α. Opposing changes in the expression of ZIP7 and ZnT7 were also observed in hyperglycemia. We conclude that subcellular free Zn 2+ redistribution in the hyperglycemic heart, resulting from altered ZIP7 and ZnT7 activity, contributes to cardiac dysfunction in diabetes. © 2017 by the American Diabetes Association.

Rationale and design of PICNIC study: nutritional intervention program in hospitalized patients with heart failure who are malnourished.

PubMed

Gámez-López, Antonio L; Bonilla-Palomas, Juan L; Anguita-Sánchez, Manuel; Moreno-Conde, Mirian; López-Ibáñez, Cristina; Alhambra-Expósito, Rosa; Castillo-Domínguez, Juan C; Villar-Ráez, Antonia; Suárez de Lezo, José

2014-04-01

Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status. It is unknown whether a nutritional intervention can modify the prognosis of these patients. The aim of this study is to assess the efficacy of a nutritional intervention on morbidity and mortality in hospitalized patients with heart failure who are malnourished. PICNIC is a multicentre, randomized, controlled trial in which hospitalized patients with heart failure and malnutrition, as defined by the Mini Nutritional Assessment, are randomly assigned to conventional management of heart failure or conventional management of heart failure and an individualized nutritional intervention consisting of 3 points: optimization of diet, specific recommendations, and prescription, if deemed necessary, of nutritional supplements. A sample size of 182 patients for a maximum follow-up of 12 months has been estimated. The primary endpoint is time to death from any cause or rehospitalization because of heart failure. Analysis is by intention to treat. PICNIC study will determine the prognostic impact of a nutritional intervention in hospitalized patients with heart failure who are malnourished. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

COULD INTERFERON-GAMMA BE A THERAPEUTIC TARGET FOR TREATING HEART FAILURE?

PubMed Central

Levick, Scott P.; Goldspink, Paul H.

2013-01-01

The cytokine interferon-gamma (IFN-γ), is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. Whilst a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will: 1) discuss the source of IFN-γ in the diseased heart; 2) summarize the data from animal studies; 3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; 4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and 5) present the clinical evidence supporting a role for IFN-γ in heart failure. PMID:23589353

Medical therapy in adults with congenital heart disease.

PubMed

Book, Wendy M; Shaddy, Robert E

2014-01-01

Heart failure is a common late complication in adults with congenital heart defects, both repaired and unrepaired. The onset of clinical heart failure is associated with increased morbidity and mortality. Some patients with congenital heart disease may benefit from medications shown to improve survival in the population with acquired heart failure, but these same therapies may be of no benefit to other patients. Further studies are needed to better guide the choice of medical therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

The Complex Dynamics of Student Engagement in Novel Engineering Design Activities

NASA Astrophysics Data System (ADS)

McCormick, Mary

In engineering design, making sense of "messy," design situations is at the heart of the discipline (Schon, 1983); engineers in practice bring structure to design situations by organizing, negotiating, and coordinating multiple aspects (Bucciarelli, 1994; Stevens, Johri, & O'Connor, 2014). In classroom settings, however, students are more often given well-defined, content-focused engineering tasks (Jonassen, 2014). These tasks are based on the assumption that elementary students are unable to grapple with the complexity or open-endedness of engineering design (Crismond & Adams, 2012). The data I present in this dissertation suggest the opposite. I show that students are not only able to make sense of, or frame (Goffman, 1974), complex design situations, but that their framings dynamically involve their nascent abilities for engineering design. The context of this work is Novel Engineering, a larger research project that explores using children's literature as an access point for engineering design. Novel Engineering activities are inherently messy: there are characters with needs, settings with implicit constraints, and rich design situations. In a series of three studies, I show how students' framings of Novel Engineering design activities involve their reasoning and acting as beginning engineers. In the first study, I show two students whose caring for the story characters contributes to their stability in framing the task: they identify the needs of their fictional clients and iteratively design a solution to meet their clients' needs. In the second, I show how students' shifting and negotiating framings influence their engineering assumptions and evaluation criteria. In the third, I show how students' coordinating framings involve navigating a design process to meet clients' needs, classroom expectations, and technical requirements. Collectively, these studies contribute to literature by documenting students' productive beginnings in engineering design. The implications span research and practice, specifically targeting how we attend to and support students as they engage in engineering design.

[Cross-border evaluation of needs for training in therapeutic education of the patient for the management in type 2 diabetes and obesity: Survey by method of nominal group with healthcare professionals].

PubMed

Pétré, Benoît; Ketterer, Frédéric; Vanmeerbeek, Marc; Scheen, André; Lair, Marie-Lise; Ziegler, Olivier; Böhme, Philip; Guillaume, Michèle

2016-10-01

The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of skills in this domain. The objective of this study is to analyze needs expressed by healthcare professionals (HP) involved in patients' management presenting a type 2 diabetes (T2D) and/or obesity and to compare them with the existing recommendations. One hundred and five PS (general practitioners, dietitians and nurses) of 3 frontier regions of French-speaking European countries (France, Belgium and Grand duchy of Luxembourg) were questioned in 12 monodisciplinary groups according to the technique of the nominal group. Needs expressed by the participants were classified in the categories of the reference table of skills to dispense TPE (National Institute for Health Prevention and Education [INPES], 2013). Among needs expressed by HP, 52 % of the votes targeted relational skills, 10 % of the skills relative to the biomedical techniques, 20 % of the skills relative to the educational techniques and 11 %, those of organization and the coordination. Seven percent of the proposals were out of the categories of the INPES. Results do not allow to establish profiles of skills according to the studied region or profession. The recognition of the TPE by the French legislation does not seem to influence in a major way the data. The needs expressed by PS in the context of this study are focused on the relation HP/patient that is the heart of the TPE. It would however be necessary to raise awareness among HP in the acquisition of the other skills which concern in particular the animation of group, the interprofessional coordination, the consideration of the environment or more generally the procedures. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.

PubMed

Louis, A; Cleland, J G; Crabbe, S; Ford, S; Thackray, S; Houghton, T; Clark, A

2001-06-01

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.

Effect of Heart Rate on Arterial Stiffness as Assessed by Pulse Wave Velocity.

PubMed

Tan, Isabella; Butlin, Mark; Spronck, Bart; Xiao, Huanguang; Avolio, Alberto

2017-07-24

Vascular assessment is becoming increasingly important in the diagnosis of cardiovascular diseases. In particular, clinical assessment of arterial stiffness, as measured by pulse wave velocity (PWV), is gaining increased interest due to the recognition of PWV as an influential factor on the prognosis of hypertension as well as being an independent predictor of cardiovascular and all-cause mortality. Whilst age and blood pressure are established as the two major determinants of PWV, the influence of heart rate on PWV measurements remains controversial with conflicting results being observed in both acute and epidemiological studies. In a majority of studies investigating the acute effects of heart rate on PWV, results were confounded by concomitant changes in blood pressure. Observations from epidemiological studies have also failed to converge, with approximately just half of such studies reporting a significant blood-pressure-independent association between heart rate and PWV. Further to the lack of consensus on the effects of heart rate on PWV, the possible mechanisms contributing to observed PWV changes with heart rate have yet to be fully elucidated, although many investigators have attributed heart-rate related changes in arterial stiffness to the viscoelasticity of the arterial wall. With elevated heart rate being an independent prognostic factor of cardiovascular disease and its association with hypertension, the interaction between heart rate and PWV continues to be relevant in assessing cardiovascular risk. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of a promotional campaign on heart-healthy menu choices in community restaurants.

PubMed

Fitzgerald, Catherine M; Kannan, Srimathi; Sheldon, Sharon; Eagle, Kim Allen

2004-03-01

The research question examined in this study was: Does a promotional campaign impact the sales of heart-healthy menu items at community restaurants? The 8-week promotional campaign used professionally developed advertisements in daily and monthly print publications and posters and table tents in local restaurants. Nine restaurants tracked the sales of selected heart-healthy menu items and comparable menu items sold before and after a promotional campaign. The percentage of heart-healthy items sold after the campaign showed a trend toward a slight increase in heart-healthy menu item selections, although it was not statistically significant. This study and others indicate that dietetics professionals must continue to develop strategies to promote heart-healthy food choices in community restaurants.

Synchronization and Random Triggering of Lymphatic Vessel Contractions.

PubMed

Baish, James W; Kunert, Christian; Padera, Timothy P; Munn, Lance L

2016-12-01

The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart-to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo.

SU-F-J-191: Dosimetric Evaluation of a Left Chestwall Patient Treated with a Compact Proton Pencil Beam Gantry Utilizing Daily Setup CBCT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maynard, M; Chen, K; Rosen, L

Purpose: To evaluate the robustness of the gradient technique for treating a multi-isocenter left chest wall patient with a compact proton pencil beam gantry. Both CBCT and stereoscopic imaging are used to facilitate daily treatment setup. Methods: To treat the elongated chest wall planning target volume (PTV) with the compact PBS system, a 28 fraction (5040 CcGE) treatment plan was created using two fields with gradient matching technique. Daily table shifts between treatment field isocenters were obtained from the record and verify system for each treatment fraction. Copies of the initial treatment plan were made for each fraction and themore » field isocenter coordinates for each plan copy were adjusted to reflect daily table shifts. Doses were re-calculated for each fraction, summed, and compared against the initial plan. Results: The table shifts (average and range) were 2.2 (−5.1–+3.9), 3.0 (−6.0–+4.0) and 3.0 (−10.1–+1.9) millimeters in the anterior-posterior, superior-inferior and right-left directions, respectively. Dose difference to the PTV, heart and ipsilateral lung were evaluated. The percentage of the PTV receiving the prescription dose decreased from 94.6% to 89.1%. The D95 of the PTV increased from 99.6% to 99.9%. The maximum dose in PTV increased from 106.6% to 109.2% and V105 increased from 1.0% to 16.5%. The V20 of the ipsilateral lung increased from 18.5% to 21.0%. The mean heart dose difference was negligible. Conclusion: Observed dose differences to lung and heart tissues due to daily setup variations remained acceptably low while maintaining sufficient dose coverage to the PTV. This initial case study demonstrates the robustness of the gradient technique to treat a large target, multi-isocenter plan with a compact proton pencil beam gantry equipped with CBCT and stereoscopic imaging modalities.« less

Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH.

PubMed

van der Velde, A Rogier; Gullestad, Lars; Ueland, Thor; Aukrust, Pål; Guo, Yu; Adourian, Aram; Muntendam, Pieter; van Veldhuisen, Dirk J; de Boer, Rudolf A

2013-03-01

In several cross-sectional analyses, circulating baseline levels of galectin-3, a protein involved in myocardial fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with heart failure (HF). The importance and clinical use of repeated measurements of galectin-3 have not yet been reported. Plasma galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324). Patient results were analyzed by categorical and percentage changes in galectin-3 level. A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients. Increasing galectin-3 levels over time, from a low to high galectin-3 category, were associated with significantly more HF hospitalization and mortality compared with stable or decreasing galectin-3 levels (hazard ratio in CORONA, 1.60; 95% confidence interval, 1.13-2.25; P=0.007; hazard ratio in COACH, 2.38; 95% confidence interval, 1.02-5.55; P=0.046). In addition, patients whose galectin-3 increased by >15% between measurements had a 50% higher relative hazard of adverse event than those whose galectin-3 stayed within ±15% of the baseline value, independent of age, sex, diabetes mellitus, left ventricular ejection fraction, renal function, medication (β-blocker, angiotensin converting enzyme inhibitor, and angiotensin receptor blocker), and N-terminal probrain natriuretic peptide (hazard ratio in CORONA, 1.50; 95% confidence interval, 1.17-1.92; P=0.001). The impact of changing galectin-3 levels on other secondary end points was comparable. In 2 large cohorts of patients with chronic and acute decompensated HF, repeated measurements of galectin-3 level provided important and significant prognostic value in identifying patients with HF at elevated risk for subsequent HF morbidity and mortality.

Small groups and long memories promote cooperation.

PubMed

Stewart, Alexander J; Plotkin, Joshua B

2016-06-01

Complex social behaviors lie at the heart of many of the challenges facing evolutionary biology, sociology, economics, and beyond. For evolutionary biologists the question is often how group behaviors such as collective action, or decision making that accounts for memories of past experience, can emerge and persist in an evolving system. Evolutionary game theory provides a framework for formalizing these questions and admitting them to rigorous study. Here we develop such a framework to study the evolution of sustained collective action in multi-player public-goods games, in which players have arbitrarily long memories of prior rounds of play and can react to their experience in an arbitrary way. We construct a coordinate system for memory-m strategies in iterated n-player games that permits us to characterize all cooperative strategies that resist invasion by any mutant strategy, and stabilize cooperative behavior. We show that, especially when groups are small, longer-memory strategies make cooperation easier to evolve, by increasing the number of ways to stabilize cooperation. We also explore the co-evolution of behavior and memory. We find that even when memory has a cost, longer-memory strategies often evolve, which in turn drives the evolution of cooperation, even when the benefits for cooperation are low.

Top-down Mass Spectrometry of Cardiac Myofilament Proteins in Health and Disease

PubMed Central

Ying, Peng; Serife, Ayaz-Guner; Deyang, Yu; Ying, Ge

2014-01-01

Myofilaments are composed of thin and thick filaments which coordinate with each other to regulate muscle contraction and relaxation. Posttranslational modifications (PTMs) together with genetic variations and alternative splicing of the myofilament proteins play essential roles in regulating cardiac contractility in health and disease. Therefore, a comprehensive characterization of the myofilament proteins in physiological and pathological conditions is essential for better understanding the molecular basis of cardiac function and dysfunction. Due to the vast complexity and dynamic nature of proteins, it is challenging to obtain a holistic view of myofilament protein modifications. In recent years, top-down mass spectrometry (MS) has emerged as a powerful approach to study isoform composition and PTMs of proteins owing to its advantage of complete sequence coverage and its ability to identify PTMs and sequence variants without a priori knowledge. In this review, we will discuss the application of top-down MS to study cardiac myofilaments and highlight the insights it provides into the understanding of molecular mechanisms in contractile dysfunction of heart failure. Particularly, recent results of cardiac troponin and tropomyosin modifications will be elaborated. The limitations and perspectives on the use of top-down MS for myofilament protein characterization will also be briefly discussed. PMID:24945106

Comparison of body composition, heart rate variability, aerobic and anaerobic performance between competitive cyclists and triathletes

PubMed Central

Arslan, Erşan; Aras, Dicle

2016-01-01

[Purpose] The aim of this study was to compare the body composition, heart rate variability, and aerobic and anaerobic performance between competitive cyclists and triathletes. [Subjects] Six cyclists and eight triathletes with experience in competitions voluntarily participated in this study. [Methods] The subjects’ body composition was measured with an anthropometric tape and skinfold caliper. Maximal oxygen consumption and maximum heart rate were determined using the incremental treadmill test. Heart rate variability was measured by 7 min electrocardiographic recording. The Wingate test was conducted to determine anaerobic physical performance. [Results] There were significant differences in minimum power and relative minimum power between the triathletes and cyclists. Anthropometric characteristics and heart rate variability responses were similar among the triathletes and cyclists. However, triathletes had higher maximal oxygen consumption and lower resting heart rates. This study demonstrated that athletes in both sports have similar body composition and aerobic performance characteristics. PMID:27190476

Enzymatic reaction paths as determined by transition path sampling

NASA Astrophysics Data System (ADS)

Masterson, Jean Emily

Enzymes are biological catalysts capable of enhancing the rates of chemical reactions by many orders of magnitude as compared to solution chemistry. Since the catalytic power of enzymes routinely exceeds that of the best artificial catalysts available, there is much interest in understanding the complete nature of chemical barrier crossing in enzymatic reactions. Two specific questions pertaining to the source of enzymatic rate enhancements are investigated in this work. The first is the issue of how fast protein motions of an enzyme contribute to chemical barrier crossing. Our group has previously identified sub-picosecond protein motions, termed promoting vibrations (PVs), that dynamically modulate chemical transformation in several enzymes. In the case of human heart lactate dehydrogenase (hhLDH), prior studies have shown that a specific axis of residues undergoes a compressional fluctuation towards the active site, decreasing a hydride and a proton donor--acceptor distance on a sub-picosecond timescale to promote particle transfer. To more thoroughly understand the contribution of this dynamic motion to the enzymatic reaction coordinate of hhLDH, we conducted transition path sampling (TPS) using four versions of the enzymatic system: a wild type enzyme with natural isotopic abundance; a heavy enzyme where all the carbons, nitrogens, and non-exchangeable hydrogens were replaced with heavy isotopes; and two versions of the enzyme with mutations in the axis of PV residues. We generated four separate ensembles of reaction paths and analyzed each in terms of the reaction mechanism, time of barrier crossing, dynamics of the PV, and residues involved in the enzymatic reaction coordinate. We found that heavy isotopic substitution of hhLDH altered the sub-picosecond dynamics of the PV, changed the favored reaction mechanism, dramatically increased the time of barrier crossing, but did not have an effect on the specific residues involved in the PV. In the mutant systems, we observed changes in the reaction mechanism and altered contributions of the mutated residues to the enzymatic reaction coordinate, but we did not detect a substantial change in the time of barrier crossing. These results confirm the importance of maintaining the dynamics and structural scaffolding of the hhLDH PV in order to facilitate facile barrier passage. We also utilized TPS to investigate the possible role of fast protein dynamics in the enzymatic reaction coordinate of human dihydrofolate reductase (hsDHFR). We found that sub-picosecond dynamics of hsDHFR do contribute to the reaction coordinate, whereas this is not the case in the E. coli version of the enzyme. This result indicates a shift in the DHFR family to a more dynamic version of catalysis. The second inquiry we addressed in this thesis regarding enzymatic barrier passage concerns the variability of paths through reactive phase space for a given enzymatic reaction. We further investigated the hhLDH-catalyzed reaction using a high-perturbation TPS algorithm. Though we saw that alternate reaction paths were possible, the dominant reaction path we observed corresponded to that previously elucidated in prior hhLDH TPS studies. Since the additional reaction paths we observed were likely high-energy, these results indicate that only the dominant reaction path contributes significantly to the overall reaction rate. In conclusion, we show that the enzymes hhLDH and hsDHFR exhibit paths through reactive phase space where fast protein motions are involved in the enzymatic reaction coordinate and exhibit a non-negligible contribution to chemical barrier crossing.

Cancer Care Coordination: a Systematic Review and Meta-Analysis of Over 30 Years of Empirical Studies.

PubMed

Gorin, Sherri Sheinfeld; Haggstrom, David; Han, Paul K J; Fairfield, Kathleen M; Krebs, Paul; Clauser, Steven B

2017-08-01

According to a landmark study by the Institute of Medicine, patients with cancer often receive poorly coordinated care in multiple settings from many providers. Lack of coordination is associated with poor symptom control, medical errors, and higher costs. The aims of this systematic review and meta-analysis were to (1) synthesize the findings of studies addressing cancer care coordination, (2) describe study outcomes across the cancer continuum, and (3) obtain a quantitative estimate of the effect of interventions in cancer care coordination on service system processes and patient health outcomes. Of 1241 abstracts identified through MEDLINE, EMBASE, CINAHL, and the Cochrane Library, 52 studies met the inclusion criteria. Each study had US or Canadian participants, comparison or control groups, measures, times, samples, and/or interventions. Two researchers independently applied a standardized search strategy, coding scheme, and online coding program to each study. Eleven studies met the additional criteria for the meta-analysis; a random effects estimation model was used for data analysis. Cancer care coordination approaches led to improvements in 81 % of outcomes, including screening, measures of patient experience with care, and quality of end-of-life care. Across the continuum of cancer care, patient navigation was the most frequent care coordination intervention, followed by home telehealth; nurse case management was third in frequency. The meta-analysis of a subset of the reviewed studies showed that the odds of appropriate health care utilization in cancer care coordination interventions were almost twice (OR = 1.9, 95 % CI = 1.5-3.5) that of comparison interventions. This review offers promising findings on the impact of cancer care coordination on increasing value and reducing healthcare costs in the USA.

Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Claffey, K.P.; Herrera, V.L.; Brecher, P.

1987-12-01

A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a lambda gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundantmore » mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source.« less

Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.

PubMed

Gay, Estelle; Bornallet, Géraldine; Gaucherand, Pascal; Doret, Muriel

2015-11-01

To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Air pollution and heart failure: Relationship with the ejection fraction

PubMed Central

Dominguez-Rodriguez, Alberto; Abreu-Afonso, Javier; Rodríguez, Sergio; Juarez-Prera, Ruben A; Arroyo-Ucar, Eduardo; Gonzalez, Yenny; Abreu-Gonzalez, Pedro; Avanzas, Pablo

2013-01-01

AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospital admission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 μm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 μg/m3 vs 4.50 ± 2.34 μg/m3, P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that short-term nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population. PMID:23538391

Myocardial bridges of the coronary arteries in the human fetal heart.

PubMed

Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

2010-09-01

During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD.

PubMed

Lalukota, Krishna; Cleland, John G F; Ingle, Lee; Clark, Andrew L; Coletta, Alison P

2004-12-01

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.

SU-F-T-119: Development of Heart Prediction Model to Increase Accuracy of Dose Reconstruction for Radiotherapy Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mosher, E; Choi, M; Lee, C

Purpose: To assess individual variation in heart volume and location in order to develop a prediction model of the heart. This heart prediction model will be used to calculate individualized heart doses for radiotherapy patients in epidemiological studies. Methods: Chest CT images for 30 adult male and 30 adult female patients were obtained from NIH Clinical Center. Image-analysis computer programs were used to segment the whole heart and 8 sub-regions and to measure the volume of each sub- region and the dimension of the whole heart. An analytical dosimetry method was used for the 30 adult female patients to estimatemore » mean heart dose during conventional left breast radiotherapy. Results: The average volumes of the whole heart were 803.37 cm{sup 3} (COV 18.8%) and 570.19 cm{sup 3} (COV 18.8%) for adult male and female patients, respectively, which are comparable with the international reference volumes of 807.69 cm{sup 3} for males and 596.15 cm{sup 3} for females. Some patient characteristics were strongly correlated (R{sup 2}>0.5) with heart volume and heart dimensions (e.g., Body Mass Index vs. heart depth in males: R{sup 2}=0.54; weight vs. heart width in the adult females: R{sup 2}=0.63). We found that the mean heart dose 3.805 Gy (assuming prescribed dose of 50 Gy) in the breast radiotherapy simulations of the 30 adult females could be an underestimate (up to 1.6-fold) or overestimate (up to 1.8-fold) of the patient-specific heart dose. Conclusion: The study showed the significant variation in patient heart volumes and dimensions, resulting in substantial dose errors when a single average heart model is used for retrospective dose reconstruction. We are completing a multivariate analysis to develop a prediction model of the heart. This model will increase accuracy in dose reconstruction for radiotherapy patients and allow us to individualize heart dose calculations for patients whose CT images are not available.« less

Lessons for Health Promotion from Selected Community-Based Heart Disease Prevention Programs.

ERIC Educational Resources Information Center

Sharma, Manoj; Galletly, Carol

1997-01-01

Discusses four key community-based coronary heart disease prevention interventions, elaborating on some of the challenges they encountered. The four interventions are the Stanford Three Community Study, Stanford Five-City Project, Minnesota Heart Health Program, and Pawtucket (Rhode Island) Heart Health Program. (SM)