Introduction: The development of liver fibrosis is characterised by dramatic changes in the biomechanical composition and mechanical properties of the extracellular matrix (ECM). Increases in matrix stiffness associated with inflammation and fibrosis are implicated in promoting cancer development. Clinical studies have demonstrated a close association between increases in liver stiffness and the incidence of hepatocellular carcinoma (HCC). The effect of changes in matrix stiffness on tissue-resident hepatic progenitor cells (HPC) is unknown. Aberrant HPC proliferation has been implicated in the pathogenesis of HCC. It was hypothesised that changes in the stiffness of the cellular microenvironment are important in regulating the behaviour of liver-resident cell populations and may promote the development of HCC. Aims: i) to determine how changes in the stiffness of the cancer cell niche might regulate proliferation, differentiation and chemotherapeutic resistance in HCC; ii) to determine the relationship between changes in liver stiffness and hepatic progenitor cell (HPC) response in rodent models of chronic liver disease; and iii) to determine whether changes in the stiffness of the HPC niche regulate proliferation and differentiation in these cells. A secondary aim of the thesis was to characterise the pattern of histological changes observed in rodent models of chronic hepatic congestion and whether this might provide insight into the effect of oedema and congestion on the development of liver fibrosis. Methods: Cell culture experiments in HCC (Huh7/ HepG2) and HPC cell lines were performed using a system of ligand-coated polyacrylamide (PA) gel supports of variable stiffness. The stiffness of the PA supports (expressed as shear modulus) was altered across a physiological change (1-12kPa) corresponding to values encountered in normal and fibrotic livers. Thiacetamide and carbon tetrachloride (CCl4) models of liver fibrosis were used to investigate the relationship between increasing liver fibrosis, changes in matrix stiffness and HPC response. The pattern of histological changes in the liver in response to hepatic congestion was assessed in two unrelated murine models of dilated cardiomyopathy; the python and CREB S133A mice. Results: Increases in matrix stiffness, as would be encountered in liver fibrosis, promote HCC cell proliferation. Increasing matrix stiffness is associated with enhanced basal and hepatocyte growth factor-mediated signalling though ERK, PKB/ Akt and STAT3. Stiffness-dependent HCC cell proliferation is modulated by β1-integrin and focal adhesion kinase. Increasing matrix stiffness is associated with a reduction in chemotherapy-induced apoptosis in HCC cells. However, following chemotherapy there was an increase in the frequency of clone-initiating cells for cells maintained in a low stiffness environment. Flow cytometry in HepG2 cells demonstrated that culture in a low stiffness environment was associated with an increase in the frequency of the stem cell markers CD44, CD133 and CXCR-4. This effect was further enhanced in the presence of chemotherapy. There is a close association between HPC numbers and liver stiffness measurements in a rat CCl4 model of chronic liver fibrosis. The major expansion in HPC numbers in this model coincides with a similarly large increase in fibrous tissue deposition. In vitro experiments using PA supports demonstrate that increasing matrix stiffness promotes the proliferation of both primary murine HPCs and an immortalised HPC line (BMOL). Changes in matrix stiffness regulate the expression of hepatocyte and biliary markers in BMOL cells. Histological studies in both the Python and CREB S133A models reveal findings consistent with acute on chronic cardiac hepatopathy (ischaemic hepatitis). Features of chronic passive congestion and centrilobular necrosis are present concurrently and develop rapidly. Bridging fibrosis and cirrhosis are not present. Conclusions: Physiologically-relevant changes in matrix stiffness regulate proliferation, differentiation, chemotherapeutic-resistance and stem cell marker expression in HCC cells. Similarly, increases in matrix stiffness are closely correlated to HPC response in vivo and regulate HPC proliferation and differentiation in vitro.

A descriptive design was used in this study to describe the feeding behaviors (as defined by changes in body position) in infants with congestive heart failure secondary to congenital heart disease. In addition, short term physiologic changes associated with the behaviors were measured through the use of pulse oximetry and cardiorespiratory monitors. Nine infants were observed in this study as they were being fed by their nurses. The method chosen was naturalistic observation. Descriptive statistics were used to analyze the demographic data and the measured physiologic variables. A point by serial correlation was conducted to describe any relationships between the position changes and the measured physiologic variables. Statistically significant relationships were found between certain positions and oxygen saturation, heart rate and respiratory rate. The results indicate that infants do experience position changes that are accompanied by changes in physiologic variables during feeding. These position changes can be categorized as infant-mediated or nurse-mediated.

A dispnéia na insuficiência cardíaca(IC) é complexa, com possível envolvimento de quimioreceptores periféricos(QP) e centrais(QC). Avaliamos a resposta de QP e QC no exercício submáximo em 15 pcts com IC e 7 ind. normais em testes ergoespirométricos de caminhada de 6 min: hipóxia isocápnica(HPX),hipercapnia hiperóxica(HPC) e ar ambiente. HPX aumentou ventilação (VE) com resposta aguda(RVA), freq. cardíaca(FC) e volume de O2 consumido;reduziu o espaço morto,distância caminhada(DC) e pressão arterial sistêmica(PAS). A HPC aumentou VE acima da HPX com RVA.Os QP têm ação maior sobre FC e PAS do que QC, apesar da maior ativação simpática.QP possuem estimulo rápido sobre VE,porém menor do que QC. / Heart failure(HF) dyspnea is complex with potential enrolment of central(CC) and peripheric chemoreceptors(PC).We investigated CC and CP behavior through submaximal exercise in 15 HF patients and 7 normal subjects in treadmill 6-minute cardiopulmonary walking tests:isocapnic hypoxia(HPO), hypercapnia hyperoxic(HCP) and room air.HPO increased:ventilation(VE) with acute ventilatory response(AVR), heart rate (HR) and O2 uptake and reduced dead space, distance walked (DW) and systemic blood pressure(SBP).The HPC improved VE above HPO level with AVR. PC have greater action on HR and SBP than CC,despite their largest sympathetic activation. PC have faster impulse on VE although be lowest than CC

The physiological and clinical considerations of centrifugal and axial pumps as ven- tricular assist devices (VADs) demands limitations on the power, size and geometry of the impellers. A typical pump design method is to rely on the characteristics of previously designed pumps with known performance using empirical equations and nondimensional parameters based on uid dynamics similarity law. Such data are widely available for industrial pumps operating in Reynolds number region of 108. VADs operate in Re < 106 and therefore the similarity concept does not apply between the industrial diagrams and the medical application of small pumps. The present dissertation employs a parametric approached analytical model to in- vestigate more than 150 axial and centrifugal pumps. The design parameters are optimised using the response surface methodology. The effect of different design parameters on the performance, force analysis and hemocompatibility of the pumps is thoroughly investigated by modelling the haemolysis through a power-law equation. The results show an explicit and consistent relationship between the number of blades, outlet width, outlet angle and the hemocompatibility of the device. Centrifu- gal pumps showed signi cantly lower probability of blood complications compared to axial pumps. The evaluation of the design characteristics helps pump designers to select their parameters accordingly for a low probability of blood complications. Furthermore, experimental techniques are employed to test more than 70 pumps in different conditions of flow, pressure and rotational speed. The experimental results validate the numerical simulations and create a database of empirical equations and data points for small axial and centrifugal pumps. The specifi c speed and speci fic diameters of the pumps are plotted on an ns − ds diagram to enable preliminary design of small pumps for VADs suitable for different stages of congestive heart failure (CHF).

Orientador: Aparecido Antônio Camacho / Banca: Evandro Zacché Pereira / Banca: Maria Lucia Gomes Lourenço / Banca: Antonio Sergio Ferraudo / Banca: Aureo Evangelista Santana / Resumo: Cães com degeneração mixomatosa da válvula mitral (DMVM) estadiados na classe II-ISACHC da insuficiência cardíaca congestiva apresentam diversas alterações dentro do estágio clínico. Evidenciando-se um ou mais sinais clínicos, aumento de câmaras cardíacas, alterações no ritmo e frequência cardíaca, bem como variabilidade da frequência cardíaca, relacionando-se ao maior ou menor predomínio do sistema nervoso autonômico parassimpático. O objetivo deste estudo foi determinar a possível existência de subclasses dentro da classe II e conhecer as variáveis que diferenciariam estas subclasses. Foram utilizadas vinte e duas variáveis na análise multivariada de 15 cães pertencentes à classe II-ISACHC da ICC. Por meio da análise de agrupamento pelo método hierárquico e não hierárquico, foram determinadas três subclasses excludentes (subclasse S1, subclasse S2 e subclasse S3). Foi possível relacionar a subclasse S1 com as variáveis de variabilidade da frequência cardíaca (e.g. NNm, PNN>50%), a subclasse S3 com as variáveis de remodelamento cardíaco (e. g. AE/Ao, DIVEd/Ao, FE%) e a subclasse S2 com câmara ventricular direita (e.g. DIVDd/Ao). Posterior à análise exploratória de fatores foram determinados três fatores (PSNA, RCFS e VDST) que relacionam as variáveis inclusas em cada fator com as subclasses. O PSNA incluiu as variáveis de variabilidade da frequência cardíaca e frequência cardíaca, o RCFS incluiu as variáveis de remodelamento cardíaco e função sistólica e o VDST integra a câm... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The dogs with myxomatous mitral valve degeneration (MMVD) staged in class II-ISACHC of congestive heart failure (CHF) have several changes within the clinical stage. Evidencing one more clinical signs, increased heart chambers, changes in heart rate and rhythm, changes in heart rate variability relating to the greater or lesser prevalence of the parasympathetic autonomic nervous system. The objective of this study was to determine the possible existence of subclasses within class II and to know the variables that would differentiate these subclasses. Twenty-two variables were used in the multivariate analysis of 15 dogs, class II of CH. Using hierarchical and non-hierarchical clustering, three exclusive subclasses (S1, S2 and S3) were determined. It was possible to relate subclass S1 to heart rate variability variables (e.g. NNm, PNN>50%), subclass S3 with cardiac remodeling variables (e.g. LA/Ao, LVDd/Ao, EF%) and subclass S2 with right ventricular chamber (e.g. RVDd/Ao). After analysis of factors were determined three factors (PSNA, RCFS and VDST) that relate the variables with the subclasses. The PSNA included variables of heart rate and heart rate variability, the RCFS contained the variables of cardiac remodeling and systolic function and the VDST enclosed the right ventricular chamber. The analysis of variance of the factors compared by subclasses determined that subclass S1 has higher values of PSNA when compared to subclasses S2 and S3. The subclass S3 had higher val... (Complete abstract click electronic access below) / Doutor

In the United States, congestive heart failure (CHF) is a cardiac condition with increasing hospitalization and rehospitalization burden to patients, families, and the healthcare system. This chronic condition is expected to affect more than 8 million people by 2030; however, not much is known about the relationship between risk factors and hospital readmissions once CHF patients are discharged to a skilled nursing facility (SNF). Applying a systems theory unbounded systems thinking, coupled with a systems-thinking approach the purpose of this quantitative, retrospective cohort study was to examine CHF hospital readmissions from SNFs within a 90-day period using a secondary data set of gender, age, race, SNF geographic location, length of SNF stay, and home health use risk factors. A binary logistic regression analysis revealed that out of 238 episodes, 99 patients were readmitted; however, no statistically significant relationship between the risk factors and readmission was found. Findings suggest that CHF readmissions from the SNF are not attributed to only quantifiable risk factors. Based on these findings, further research can support social change through multifaceted quantitative and qualitative systemic analyses to identify and inform how healthcare organizations can better assist the elderly population with CHF and improve future post-acute community-based health education and prevention programs.

With more than 700,000 new diagnoses annually, congestive heart failure (CHF) is a chronic condition that affects the chambers of the heart. When not managed correctly, the disease rapidly progresses to substantial fluid volume overload that impacts activities of daily living and the overall quality of life. The financial implications for poor CHF management cost a mean annual medical expenditure of $33,427 per patient per year. The need for a diagnostic and prognostic at-home protocol is needed in the medical community, as there is currently no such tool on the market. Donabedian's framework was used to guide the formulation and interpretation of this research. The purpose of this project was to design a CHF protocol using evidence-based research for clinicians making home visits to homebound patients with a primary diagnosis of CHF with an individualized protocol focusing on disease management, in home support system, knowledge base and financial factors for homebound patients. The protocol was released through a snowballing campaign to clinicians who work with CHF, transitional care, or homecare who then evaluated the protocol on its perceived efficacy if integrated into practice. Findings were analyzed using simple descriptive statistics by 32 nurses and other health care professionals who responded work in home care, cardiology, medical surgical nursing hospitalists, or skilled nursing facilities. Thirty-one of the 32 respondents deemed the protocol useful and stated a clinical need of protocol as evidenced by completed the AGREE II Questionnaire. The findings demonstrate that the CHF Practice Protocol provides clinicians with an evidence-based guidance to manage homebound patients with CHF on a small scale.

Abstract African Americans are disproportionately affected by heart failure, with prevention and treatment of heart failure being a public health concern in the United States. The purpose of this retrospective quantitative study was to examine the primary variable race, specifically African Americans, and how this variable relates to 30-day readmission post discharge when controlled with geographic location (urban vs. rural), gender, and insurance status. The expanded chronic care model was used as a framework to shape health promotion, prevention efforts, and social determinants of health and to enhance community involvement related to chronic disease issues. The research questions were focused on determining a relationship among African Americans being at a higher risk for 30-day readmission than others using selected control variables. Secondary data were collected for 565 patients diagnosed with congestive heart failure from the 2015 Hospital Inpatient Discharges data set and analyzed using simple and multivariate logistic regression methods to answer research questions and test hypotheses. Key results of the simple logistic regression revealed that African Americans were 1.7 times more likely to be readmitted than other races and 1.3 times more likely to be readmitted than Caucasians. The multiple logistic regression revealed race, gender and geographic location (urban) as significant predictors of readmission among African Americans. Insurance status revealed no significance for readmission among African Americans. Implications for social change from this study may include policy implementation at the family, organizational, and societal levels, such as policy related to education on establishing a surveillance system that identifies those in the population who are at risk and more vulnerable to social and health care disparities.

African Americans suffer disproportionately higher incidence of congestive heart failure (CHF) at an earlier age of onset and with more rapid progression compared to other races. Due to this escalating prevalence of CHF within the African American population and the lack of culturally responsive support for the caregiving role, African American family caregivers of adult CHF patients face greater challenges and suffer increased caregiver burden, stress, depression, and financial strain compared to European American caregivers. The purpose of this project was to conduct a systematic literature review to find the recommendations that target African American family caregivers of adult CHF patients. The Joanna Briggs Institute model for systematic review (JBIM-SR), and the caregiver stress theory proposed by Tsai, guided this project. A review of multiple databases yielded 118,078 articles. After removal of duplicates and exclusion of articles not consistent with the purpose of the review, 1 article was selected. A second reviewer completed an independent search of the databases using the same exclusion/inclusion criteria and identified the same review. The selected article was analyzed and graded using the JBIM-SR grading tools. Family Heart Failure Home Care, a telephone coaching intervention adapted to the cultural preferences of the African American family caregivers of adult CHF patients, was suggested as an effective culturally sensitive intervention. Results of this project can promote positive social change by improving the care and well-being of the African American community. Nurses at the project site can use the findings to provide evidence-based care to the African American family caregivers of adult CHF patients.

Abstract not available