Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Magnesium – association with inflammation and renal disease in systemic lupus erythematosus

Introduction: Recent studies suggest that magnesium deficiency may play a role in inflammation. In diabetes and cardio-vascular diseases, conditions with a component of chronic inflammation, C–reactive protein levels are higher and associated with low serum magnesium. The objective of this study is to evaluate serum magnesium levels in patients with systemic lupus erythematosus and its potential association with inflammation and renal manifestations. Methods: All patients with systemic lupus erythematosus followed in a Systemic Immune Diseases Unit, from January 2012 until January 2014, were included in this cross sectional analysis. Patients with infection, neoplasia, liver failure and chronic kidney disease (stage > 3) were excluded. Clinical information and laboratory results (serum magnesium, C-reactive protein, erythrocyte sedimentation rate, serum creatinine and spot urine test) were collected. A multivariate analysis was performed to explore possible predictive factors for hypomagnesaemia. Results: One hundred and two patients were included (94.1% female, 21-86 years). 33.4% had hypertension, 8.8% had diabetes and 20.6% had hypomagnesaemia (< 1.8mg/dL). There were no significant differences between the inflammatory parameters of patients with hypomagnesaemia or normomagnesaemia. Serum magnesium was significantly lower with increasing comorbidities (p = 0.01). Leukocyturia was significantly higher in the hypomagnesaemia group (p = 0.03) and haematuria had a negative correlation with serum magnesium (-0.23, p < 0.05). Multivariate analysis showed that patients with hypertension and diabetes had higher risk of hypomagnesaemia: OR 42.29 (95% CI, 1.43-1249.31). Leukocyturia was also individually and independently associated with hypomagnesaemia: OR 8.37 (95% CI, 1.40-49.97). Conclusion: The presence of hypomagnesaemia in our patients with systemic lupus erythematosus was high. There was no association between the levels of serum magnesium and the inflammatory parameters. Increasing comorbidities and leukocyturia were independent predictors of lower serum magnesium. Finally, the association of leukocyturia and haematuria with lower serum magnesium may suggest a relationship with a higher disease activity.

MONTENEGRO SKIN TEST AND AGE OF SKIN LESION AS PREDICTORS OF TREATMENT FAILURE IN CUTANEOUS LEISHMANIASIS

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Unexpected Triggers for Pheochromocytoma-Induced Recurrent Heart Failure

Pheochromocytoma crisis typically presents as paroxysmal episodes of headache, tachycardia, diaphoresis or hypertension. We describe an uncommon case of recurrent non-hypertensive heart failure with systolic dysfunction in a young female due to pheochromocytoma compression. It presented as acute pulmonary oedema while straining during pregnancy and later on as cardiogenic shock after a recreational body massage. Such crisis occurring during pregnancy is rare. Moreover, of the few reported cases of pheochromocytoma-induced cardiogenic shock, recreational body massage has not yet been reported as a trigger for this condition.

The Oncological and Functional Risks of the Organ Preservation Experimental Treatment Approach

We increasingly face conservative surgery for rectal cancer and even the so called ‘wait and see’ approach, as far as 10–20% patients can reach a complete pathological response at the time of surgery. But what can we say to our patients about risks? Standard surgery with mesorectal excision gives a <2% local recurrence with a post operative death rate of 2–8% (may reach 30% at 6 months in those over 85), but low AR has some deterioration in bowel function and in low cancer a permanent stoma may be required. Also a long-term impact on urinary and sexual function is possible. Distant metastasis rate seem to be identical in the standard and conservative approach. It is difficult to evaluate conservative approach because a not clear standardization of surgery for low rectal cancer. Rullier et al tried to clarify, and they found identical results for recurrence (5–9%), disease free survival (70%) at 5y for coloanal anastomosis and intersphinteric resection. Other series have found local recurrence higher than with standard approach and functional results may be worse and, in some situations, salvage therapy is compromised or has more complications. In this context, functional outcomes are very important but most studies are incomplete in measuring bowel function in the context of conservative approach. In 2005 Temple et al made a survey of 122/184 patient after sphinter preserving surgery and found a 96.9% of incomplete evacuation, 94.4% clustering, 93.2% food affecting frequency, 91.8% gas incontinence and proposed a systematic evaluation with a specific questionnaire. In which concerns ‘Wait and see’ approach for complete clinical responders, it was first advocated by Habr Gama for tumors up to 7cm, with a low locoregional failure of 4.6%, 5y overall survival 96%, 72% for disease free survival; one fifth of patients failed in the first year; a Dutch trial had identical results but others had worse recurrence rates; in other series 25% of patients could not be salvaged even with APR; 30% have subsequent metastatic disease what seems equal for ‘wait and see’ and operated patients. In a recent review Glynne Jones considers that all the evaluated ‘wait and see’ studies are heterogeneous in staging, inclusion criteria, design and follow up after chemoradiation and that there is the suggestion that patients who progress while under observation fare worse than those resected. He proposes long-term observational studies with more uniform inclusion criteria. We are now facing a moment where we may be more aggressive in early cancer and neoadjuvant treatment to be more conservative in the subsequent treatment but we need a better stratification of patients, better evaluation of results and more clear prognostic markers.

Liver Depurative Techniques: A Single Liver Transplantation Center Experience

In a liver transplant (LT) center, treatments with Prometheus were evaluated. The main outcome considered was 1 and 6 months survival. Methods. During the study period, 74 patients underwent treatment with Prometheus; 64 were enrolled,with a mean age of 51 13 years; 47men underwent 212 treatments (mean, 3.02 per patient). The parameters evaluated were age, sex, laboratorial (liver enzymes, ammonia) and clinical (model for end-stage liver disease and Child-Turcotte-Pugh score) data. Results. Death was verified in 23 patients (35.9%) during the hospitalization period, 20 patients (31.3%) were submitted to liver transplantation, and 21 were discharged. LT was performed in 4 patients with acute liver failure (ALF, 23.7%), in 7 patients with acute on chronic liver failure (AoCLF, 43.7%), and in 6 patients with liver disease after LT (30%). Seven patients who underwent LT died (35%). In the multivariate analysis, older age (P ¼ .015), higher international normalized ratio (INR) (P ¼ .019), and acute liver failure (P ¼ .039) were independently associated with an adverse 1-month clinical outcome. On the other hand, older age (P ¼ .011) and acute kidney injury (P ¼ .031) at presentation were both related to worse 6-month outcome. For patients with ALF and AoCLF we did not observe the same differences. Conclusions. In this cohort, older age was the most important parameter defining 1- and 6-month survival, although higher INR and presence of ALF were important for 1-month survival and AKI for 6-month survival. No difference was observed between patients who underwent LT or did not have LT.

Percutaneous Treatment of Mitral Valve Regurgitation: Initial Experience with the MitraClip Device

INTRODUCTION: Mitral regurgitation (MR) is the most common valvular disease and has recently become the target of a number of percutaneous approaches. The MitraClip is virtually the only device for which there is considerable experience, with more than 20,000 procedures performed worldwide. OBJECTIVE: To describe our initial experience of the percutaneous treatment of MR with the MitraClip device. METHODS: We describe the first six MitraClip cases performed in this institution (mean age 58.5 ± 13.1 years), with functional MR grade 4+ and New York Heart Association (NYHA) heart failure class III or IV (n=3), with a mean follow-up of 290 ± 145 days. RESULTS: Procedural success (MR ≤ 2+) was 100%. Total procedure time was 115.8 ± 23.7 min, with no in-hospital adverse events and discharge between the fourth and eighth day, and consistent improvement in the six-minute walk test (329.8 ± 98.42 vs. 385.33 ± 106.95 m) and in NYHA class (three patients improved by two NYHA classes). During follow-up there were two deaths, in two of the four patients who had been initially considered for heart transplantation. CONCLUSION: In patients with functional MR the MitraClip procedure is safe, with both a high implantation and immediate in-hospital success rate. A longer follow-up suggests that the clinical benefit decreases or disappears completely in patients with more advanced heart disease, namely those denied transplantation or on the heart transplant waiting list.

An approach to teach Calculus/Mathematical Analysis (for engineering students) using computers and active learning – its conception, development of materials and evaluation

Dissertação para obtenção do Grau de Doutor em Ciências da Educação

The impact of sizeof the firm and exchange rate in the export propensity of domestic and foreign owned firms in a developing country: A study of the Brazilian exporters

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Rate of reversion of hepatosplenic schistosomiasis after specific therapy

Seventy patients with hepatosplenic schistosomiasis were treated with oxamniquine. The patients lived iti an endemic area and were evaluated 6, 18 and 24 months after treatment, during which time transmission in the area was interrupted. After treatment, clinical improvement occurred in 49 (70%) of the patients, as seen by reduction in visceromegaly and reversion of liver nodules. Reversion of hepatosplenic disease occurred in 28 (40%) patients and in liver nodularity in 26 (47.3%)patients after 24 months. Reversion of hepatosplenic disease was seen in 12 (21%) patients and liver nodules disappeared in 4 (8.5%) as early as 6 months after treatment. In general, hepatosplenomegaly reverses earlier than liver nodularity. Itis notable that reversion of hepatosplenic disease occurred in many individuals with a history ofprevious treatment and also in some with advanced age. In four cases this clinical form of the disease had existed for 20 years. Therefore, there must exist factors other than age and duration of the condition which determine the reversibility of this clinical form. Ourresults reinforce the concept that, in patients with hepatosplenic disease without esophageal hemorrhages, specific treatment shouldpreceed surgical intervention even in those with a history of previous treatment. At least 18 months should be allowed for the ejfects of treatment to be manifest.

Rate of action of schistosomicides in mice infected with Schistosoma mansoni

Mice infected with adult Schistosoma mansoni were dosed with a single oral dose of 125 or 250 mg/kg oltipraz, 50 or 100 mg/kg oxamniquine, or 200 or 400 mg/kg praziquantel. The mortality rate of worms and oogram changes were determined between 1 and 16 weeks after dosing. The time required between dosing and postmortem to obtain maximum effectiveness was 1 week for praziquantel, 2 weeks for oxamniquine and 8 weeks for oltipraz. Changes in oograms persisted throughout most of the experiment, although relapse has been observed at the 4th week on.

Tetanus as a cause of acute renal failure: possible role of rhabdomyolysis

To study the frequency and examine the role of rhabdomyolysis in the acute renalfailure in tetanus 18 patients with the diagnosis of generalized tetanus consecutively admitted to the infectious disease hospital were evaluated. Ofthese 14 were male and 4female with mean age of 31.8± 2.0 years. Except for mild proteinuria recorded in 9 patients, the urinalysis were unremarkable. Serum creatinine higher than 1.4mg/dl was recorded in 39% of the patients, abnormal levels of CPK in 87,5% and serum myoglobin greater than 120µg/l in 39% of the patients. Oliguria was documented in one patient and none required diafysis therapy. No correlation wasfound between renal failure and myoglobin and/or CPK serum levels. Acute renalfailure in tetanus was not infrequent; usualfy it was non-oliguric, mild and transient and not related to the severity of the disease or to serum levels of myoglobin and/or CPK.

Determinants of entrepreneurship: Are women different?

In this paper we investigate, for the first time, how individual determinants of entrepreneurship - such as age, income, education, work status, skills, access to networks and fear of failure - differ between males and females. We conduct our exercise using individual data provided by the Global Entrepreneurship Monitor (GEM), available for 46 countries, between 2001 and 2004. The literature on entrepreneurship has uncovered differences in the rate of entrepreneurship between men and women, with women generally displaying lower entrepreneurial activity than men. This is important since, as we show, entrepreneurial activity is positively related across countries with the female to male entrepreneurial ratio. We examine total entrepreneurship rates, as well as entrepreneurship driven by opportunity and by need. We find that indeed entrepreneurial activity rates are lower for females across all but one of the countries in the sample. Looking at categorical groups – by age interval, education, work status, etc. – we find that female entrepreneurial rates are significantly lower than for males. For the first time we test for differences in the characteristics of female and male entrepreneurs and find that female entrepreneurs are slightly older, more frequently at home or not working, lower income and lower educated, and less access to business networks than their male counterparts. AS to the determinants of entrepreneurial rates themselves, the main differences across genders are the lower impact of secondary education and the larger impact of skills and fear of failure in female entrepreneurial rates relative to males. Results for entrepreneurship by opportunity and by necessity confirm the larger importance of specific skills for women creating new businesses,. Our results suggest that facilitating access to business networks and specific business skills are the most powerful instruments to increase the rates of female entrepreneurship.

Análise de custo-efectividade da terapêutica de ressincronização cardíaca : avaliação da selecção baseada na dessincronia mecânica

RESUMO - A Terapêutica de Ressincronização Cardíaca (TRC) apresenta benefícios significativos na classe funcional, função ventricular, hospitalização e mortalidade. É uma técnica com custos elevados e, com os actuais métodos de selecção de doentes, a taxa de não-respondedores ronda os 30%. Objectivo: Compreender se a inclusão da dessincronia mecânica (DM) na selecção de doentes para TRC contribui para a sua relação custo-efectividade, na perspectiva do Serviço Nacional de Saúde português. Metodologia: Estudo prospectivo baseado em coortes histórias de 12 meses de dois grupos submetidos a TRC com desfibrilhador, o grupo de intervenção com doentes seleccionados com inclusão da DM (n=133) e o de controlo com selecção baseada exclusivamente nas recomendações internacionais (n=71). Reuniram-se dados clínicos e de custos nos 12 meses subsequentes à implantação, para cálculo do rácio custo-efectividade incremental (RCEI). Resultados: O grupo de intervenção apresentou uma sobrevivência de 91% e o de controlo de 93%, aos 12 meses (p=0,335). O grupo de intervenção apresentou 60 re-internamentos e o de controlo 46 re-internamentos por qualquer causa aos 12 meses (p=0,032), com RCEI=6.886,09€/re-internamento evitado. O grupo de intervenção apresentou 19 re-internamentos e o de controlo apresentou 31 re-internamentos por Insuficiência Cardíaca (IC) descompensada aos 12 meses (p<0,001), com RCEI=2.686,26€/re-internamento por IC descompensada evitado. Relativamente à melhoria da classe funcional e da fracção de ejecção não foi possível estabelecer associações com custos (p>0,05). Conclusão: É seguro afirmar que recomendar a selecção com inclusão da DM, nos hospitais com capacidade instalada, é um passo positivo na redução de custos com re-internamentos de doentes com TRC.

Serial heart rate changes in rats inoculated by conjunctival instillation of Trypanosoma cruzi obtained from bug faeces

The cardiac effects of experimentally induced myocarditis, when the parasite is obtained from mouse blood, are well known. However, the consequences of the infection when the parasites are obtained from bug faeces are less well defined. In the present investigation, we have used the "Y" strain of Trypanosoma cruzi, which was maintained in Rhodnius prolixus by repeated passages in mice. The faeces of 30 infected bugs were collected, the number of parasites counted and 4,000 parasites inoculated by the conjunctival route in 60 rats. Twenty-nine other rats received faeces from noninfected bugs (sham-inoculated controls) and 40 were used as normal controls. The heart rate of the three groups of animals was recorded under general anesthesia with ether. The heart rate, at day 0 pre-inoculation, was similar in the three groups of animals (Controls: 379 ± 27 beats/min Mean ± SD; Sham-inoculated: 366 ± 31; Infected: 351 ± 29) (p> 0.05). In the infected animals, the mean heart rate began to increase significantly by day 12 following infection (375 ± 31), reaching the highest values between days 18 (390 ± 33) and 21 (403 ± 33) and returned to baseline by day 30 (359 ± 28) (p< 0.05). The heart rate changes were statistically different from those observed in the sham-inoculated controls and in the control animals. Therefore, these heart rate changes were provoked by the Trypanosoma cruzi-induced infection. Thus, it appears that irrespective of the source of the parasite and route of inoculation Trypanosoma cruziacute infection provokes a transient sinus tachycardia.