Development of Monoolein-based lipofection vectors for therapeutic siRNA delivery

Tese de Doutoramento em Biologia Molecular e Ambiental - Especialidade em Biologia Celular e Saúde

Normal values of echocardiographic measurements. A population-based study

OBJECTIVE: To describe echocardiographic measurements and left ventricular mass in a population sample of healthy adults inhabitants of the urban region of Porto Alegre. METHODS: An analytical, observational, population-based, cross-sectional study was done. Through a multi-stage probability sample, 114 individuals were selected to be submitted to a M-mode and two-dimensional echocardiogram with color Doppler. The analyses were restricted to healthy participants. Echocardiographic measurements were described by mean, standard deviation, 95 percentile and 95% confidence limits. RESULTS: A total of 100 healthy participants, with several characteristics similar to those from the original population, had a complete and reliable echocardiographic examination. The measurements of aorta, left atrium, interventricular septum, left ventricle in systole and diastole, left posterior wall and left ventricular mass, adjusted or not for body surface area or height, were significantly higher in males. The right ventricle size was similar among the genders. Several echocardiographic measurements were within standard normal limits. Interventricular septum, left posterior wall and left ventricular mass, adjusted or not for anthropometric measurements, and aortic dimensions had lower mean and range than the reference limits. CONCLUSION: The means and estimates of distribution for the measurements of interventricular septum, left posterior wall and left ventricular mass found in this survey were lower than those indicated by the international literature and accepted as normal limits.

Detection of coronary artery disease based on the calcification index obtained by helical computed tomography

OBJECTIVE: To assess the relation between coronary artery disease and the calcification index on helical computed tomography. METHOD: We studied 22 patients (ages ranging from 40 to 70 years) who underwent coronary angiography because of chest pain suggestive of angina pectoris. Findings on coronary angiography were classified as follows: significant obstructive disease (stenosis > or = 50%), nonobstructive disease (stenosis <50%), and no disease. With no previous knowledge of the results of the coronary angiography and within 7 days, helical computed tomography of the chest was performed. Then, data of the coronary angiography were correlated with the calcification index obtained by helical computed tomography. RESULTS: The sensitivity of helical computed tomography to the presence of significant obstructive lesions on coronary angiography was 87.5%, specificity was 100%, and negative and positive predictive values were 75% and 100%, respectively. The mean calcification index was greater in patients with severe coronary lesions, mainly when involvement of 2 or 3 vessels occurred, than that in patients with no coronary artery disease or with nonobstructive coronary artery lesions (p<0.05). CONCLUSION: Helical computed tomography is an effective method for detecting and quantifying coronary artery calcification, and it has proved to be sensitive to and specific for the noninvasive diagnosis of coronary artery stenosis.

Perfil de habilidades motoras finas de crianças com e sem perturbação do espectro do autismo, na zona norte de Portugal: um estudo comparativo

Dissertação de mestrado em Educação Especial (área de especialização em Intervenção Precoce)

Analysis of the Prevalence of Ventricular Late Potentials in the Late Phase of Myocardial Infarction Based on the Site of Infarction

OBJECTIVE: The initial site of myocardial infarction (MI) may influence the prevalence of ventricular late potentials (VLP), high-frequency signals, due to the time course of ventricular activation. The prevalence of VLP in a period of more than 2 years after acute MI was assessed focusing on the initially injured wall . METHODS: The prevalence of VLP in a late phase after MI (median of 924 days) in anterior/antero-septal and inferior/infero-dorsal wall lesion was analyzed using signal-averaged electrocardiogram in time domain. The diagnostic performance of the filters employed for analysis on was tested at high-pass cut-off frequencies of 25 Hz, 40 Hz and 80 Hz. RESULTS: The duration of the ventricular activation and its terminal portion were larger in inferior than anterior infarction, at high-pass cut-off frequencies of 40 Hz and 80 Hz. In patients with ventricular tachycardia, these differences were more remarked. The prevalence of ventricular late potentials was three times greater in inferior than anterior infarction. CONCLUSION: Late after myocardial infarction, the prevalence and the duration of ventricular late potentials are greater in lesions of inferior/infero-dorsal than anterior/antero-septal wall confirming their temporal process, reflecting their high-frequency content.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde

A study of the interaction between national and corporate culture in a selection of Irish based companies

This research studies the phenomenon of national and corporate culture. National culture is the culture the members of a country share and corporate culture is a subculture which members of an organisation share (Schein, 1992). The objective of this research is to reveal if the employees within equivalent Irish and American companies share the same corporate and national culture and to ascertain if, within each company, there is a link between national culture and corporate culture. The object of this study is achieved by replicating research which was conducted by Shing (1997) in Taiwan. Hypotheses and analytical tools developed by Shing are employed in the current study to allow comparison of results between Shing’s study and the current study. The methodology used, called for the measurement and comparison of national and corporate culture in two equivalent companies within the same industry. The two companies involved in this study are both located in Ireland and are of American and Irish origin. A sample of three hundred was selected and the response rate was 54%. The findings from this research are: (1) The two companies involved had different corporate cultures, (2) They had the same national culture, (3) There was no link between national culture and corporate culture within either company, (4) The findings were not similar to those of Shing (1997). The implication of these findings is that national and corporate culture are separate phenomena therefore corporate culture is not a response to national culture. The results of this research are not reflected in the finding’s of Shing (1997), therefore they are context specific. The core recommendation for management is that, corporate culture should take account of national culture. This is because although employees recognise the espoused values of corporate culture (Schein, 1992), they are at the same time influenced by a much stronger force, their national culture.

Blood Pressure Control in Hypertensive Patients in the "Hiperdia Program": A Territory-Based Study

Background:Systemic hypertension is highly prevalent and an important risk factor for cardiovascular events. Blood pressure control in hypertensive patients enrolled in the Hiperdia Program, a program of the Single Health System for the follow-up and monitoring of hypertensive patients, is still far below the desired level.Objective:To describe the epidemiological profile and to assess blood pressure control of patients enrolled in Hiperdia, in the city of Novo Hamburgo (State of Rio Grande do Sul, Brazil).Methods:Cross-sectional study with a stratified cluster random sample, including 383 adults enrolled in the Hiperdia Program of the 15 Basic Health Units of the city of Porto Alegre, conducted between 2010 and 2011. Controlled blood pressure was defined as ≤140 mmHg × 90 mmHg. The hypertensive patients were interviewed and their blood pressure was measured using a calibrated aneroid device. Prevalence ratios (PR) with 95% confidence interval, Wald's χ2 test, and simple and multiple Poisson regression were used in the statistical analysis.Results:The mean age was 63 ± 10 years, and most of the patients were females belonging to social class C, with a low level of education, a sedentary lifestyle, and family history positive for systemic hypertension. Diabetes mellitus (DM) was observed in 31%; adherence to the antihypertensive treatment in 54.3%; and 33.7% had their blood pressure controlled. DM was strongly associated with inadequate BP control, with only 15.7% of the diabetics showing BP considered as controlled.Conclusion:Even for hypertensive patients enrolled in the Hiperdia Program, BP control is not satisfactorily reached or sustained. Diabetic hypertensive patients show the most inappropriate BP control.

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

Sudden Cardiac Death in Brazil: A Community-Based Autopsy Series (2006-2010)

Background: Sudden cardiac death (SCD) is a sudden unexpected event, from a cardiac cause, that occurs in less than one hour after the symptoms onset, in a person without any previous condition that would seem fatal or who was seen without any symptoms 24 hours before found dead. Although it is a relatively frequent event, there are only few reliable data in underdeveloped countries. Objective: We aimed to describe the features of SCD in Ribeirão Preto, Brazil (600,000 residents) according to Coroners’ Office autopsy reports. Methods: We retrospectively reviewed 4501 autopsy reports between 2006 and 2010, to identify cases of SCD. Specific cause of death as well as demographic information, date, location and time of the event, comorbidities and whether cardiopulmonary resuscitation (CPR) was attempted were collected. Results: We identified 899 cases of SCD (20%); the rate was 30/100000 residents per year. The vast majority of cases of SCD involved a coronary artery disease (CAD) (64%) and occurred in men (67%), between the 6th and the 7th decades of life. Most events occurred during the morning in the home setting (53.3%) and CPR was attempted in almost half of victims (49.7%). The most prevalent comorbidity was systemic hypertension (57.3%). Chagas’ disease was present in 49 cases (5.5%). Conclusion: The majority of victims of SCD were men, in their sixties and seventies and the main cause of death was CAD. Chagas’ disease, an important public health problem in Latin America, was found in about 5.5% of the cases.

Model-based diagnosis system: application to constructed wetlands

Report for the scientific sojourn carried out at the Model-based Systems and Qualitative Reasoning Group (Technical University of Munich), from September until December 2005. Constructed wetlands (CWs), or modified natural wetlands, are used all over the world as wastewater treatment systems for small communities because they can provide high treatment efficiency with low energy consumption and low construction, operation and maintenance costs. Their treatment process is very complex because it includes physical, chemical and biological mechanisms like microorganism oxidation, microorganism reduction, filtration, sedimentation and chemical precipitation. Besides, these processes can be influenced by different factors. In order to guarantee the performance of CWs, an operation and maintenance program must be defined for each Wastewater Treatment Plant (WWTP). The main objective of this project is to provide a computer support to the definition of the most appropriate operation and maintenance protocols to guarantee the correct performance of CWs. To reach them, the definition of models which represent the knowledge about CW has been proposed: components involved in the sanitation process, relation among these units and processes to remove pollutants. Horizontal Subsurface Flow CWs are chosen as a case study and the filtration process is selected as first modelling-process application. However, the goal is to represent the process knowledge in such a way that it can be reused for other types of WWTP.

Estudi i revalorització dels paisatges culturals de l'alta muntanya pirinenca: la vall del Madriu (Andorra), patrimoni de la humanitat de la UNESCO

Estudi arqueològic integrat de la vall del Madriu-Perafita-Claror (Andorra) iniciat al 2004 sota la coordinació de l’ICAC. L’estudi s’insereix en la declaració de la vall com a Patrimoni de la Humanitat (UNESCO). Las recerques s’enfoquen des de l’Arqueologia del Paisatge, de manera diacrònica i pluridisciplinar, fent especial atenció a les relacions de les societats amb el medi. Les restes arqueològiques treballades s’associen a activitats ramaderes, metal•lúrgiques i de carboneig. La recerca paleoecològica se centra en sediments lacustres, torbosos i arqueològics. L’any 2006, s’han analitzat a alta resolució temporal dues seqüencies palinològiques: l’estany Blau (2471 m) i la torbera de Bosc dels Estanyons (2180 m), obtenint les principals fases d’explotació i antropització d’aquest espai altimontà, així com l’evolució del paisatge en els darrers 11000 anys . La campanya de camp s’ha centrat en l’obtenció de mostres de pluja pol•línica referencial a la vall i en el sondatge de l’estany Forcat (2539 m). Un total de tres mostres han estat enviades a datar per C14. Els treballs arqueològics s’han centrat en l’excavació de sondejos de diagnòstic als jaciments de Basses de Setut (2325 m) i Pleta de les Bacives ( 2530 m) i en la realització de prospeccions a les capçaleres de les valls de Madriu, Perafita i Claror. S’han documentat estructures arqueològiques i s’han realitzat estudis antracològics dels sediments excavats en aquestes. S’ha realitzat un transecte altitudinal de carboneres al llarg de la vall per tal de enregistrar una major diversitat cronològica dels espais de carboneig. S’han enviat datacions C14 per tal de determinar la cronologia de les estructures. Les datacions del 2005 mostren una intensa ocupació ramadera i de carboneig a partir del segle XIV, en època baixmedieval i moderna, així com un establiment metal·lúrgic d’època romana.

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Diabetes care in Switzerland: good, but perfectible: a population-based cross-sectional survey.

BACKGROUND: While Switzerland invests a lot of money in its healthcare system, little is known about the quality of care delivered. The objective of this study was to assess the quality of care provided to patients with diabetes in the Canton of Vaud, Switzerland. METHODS: Cross-sectional study of 406 non-institutionalized adults with type 1 or 2 diabetes. Patients' characteristics, diabetes and process of care indicators were collected using a self-administered questionnaire. Process indicators (past 12 months) included HbA1C check among HbA1C-aware patients, eye assessment by ophtalmologist, microalbuminuria check, feet examination, lipid test, blood pressure and weight measurement, influenza immunization, physical activity recommendations, and dietary recommendations. Item-by-item (each process of care indicator: percentage of patients having received it), composite (mean percentage of recommended care: sum of received processes of care / sum of possible recommended care), and all-or-none (percentage of patients receiving all specified recommended care) measures were computed. RESULTS: Mean age was 64.4 years; 59% were men. Type 1 and type 2 diabetes were reported by 18.2% and 68.5% of patients, respectively, but diabetes type remained undetermined for almost 20% of patients. Patients were treated with oral anti-diabetic drugs (50%), insulin (23%) or both (27%). Of 219 HbA1C-aware patients, 98% reported ≥ one HbA1C check during the last year. Also, ≥94% reported ≥ one blood pressure measurement, ≥ one weight measurement or lipid test, and 68%, 64% and 56% had feet examination, microalbuminuria check and eye assessment, respectively. Influenza immunization was reported by 62% of the patients.The percentage of patients receiving all processes of care ranged between 14.2%-16.9%, and 46.6%-50.7%, when considering ten and four indicators, respectively. Ambulatory care utilization showed little use of multidisciplinary care, and low levels of participation in diabetes-education classes. CONCLUSIONS: While routine processes-of-care were performed annually in most patients, diabetes-specific risk screenings, influenza immunization, physical activity and dietary recommendations were less often reported; this was also the case for multidisciplinary care and participation in education classes. There is room for diabetes care improvement in Switzerland. These results should help define priorities and further develop country-specific chronic disease management initiatives for diabetes.

Who Matters in Coordination Problems?

We consider a common investment project that is vulnerable to a self-ful lling coordination failure and hence is strategically risky. Based on their private information, agents - who have heterogeneous investment incentives - form expectations or 'sentiments' about the project's outcome. We find that the sum of these sentiments is constant across di erent strategy profiles and it is independent of the distribution of incentives. As a result, we can think of sentiment as a scarce resource divided up among the di erent payo types. Applying this nding, we show that agents who bene t little from the project's success have a large impact on the coordination process. The agents with small bene ts invest only if their sentiment towards the project is large per unit investment cost. As the average sentiment is constant, a subsidy decreasing the investment costs of these agents will \free up" a large amount of sentiment, provoking a large impact on the whole economy. Intuitively, these agents, insensitive to the project's outcome and hence to the actions of others, are in uential because they modify their equilibrium behavior only if the others change theirs substantially.