DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

Five-Year Review of an International Clinical Research-Training Program

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background.

Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA

A conceptual model of a brand's presence on Facebook aligned with teenagers' motivations and marketing strategies

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

Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance

Dissertação para obtenção do Grau de Mestre em Biotecnologia

How to potentiate the business model of Mobitto for B2B?

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

Dissecting gastrointestinal dysfunction and inflammation in a “pre-motor” rodent model of Parkinson’s disease

Research on Parkinson’s disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal (NS) pathway; also, post-mortem studies have demonstrated that the noradrenergic and the serotonergic transmitter systems are also affected (Jellinger, 1999). Degeneration of these neuronal cell bodies is generally thought to start prior to the loss of dopaminergic neurons in the NS pathway and precedes the appearance of the motor symptoms that are the “hallmark” of PD. Gastrointestinal (GI) motility is often disturbed in PD, manifesting chiefly as impaired gastric emptying and constipation. These GI dysfunction symptoms may be the result of a loss in noradrenergic and serotonergic innervation. GI deficits were evaluated using an organ bath technique. Groups treated with different combinations of neurotoxins (6-OHDA alone, 6-OHDA + pCA or 6-OHDA + DSP-4) presented significant differences in gut contractility compared to control groups. Since a substantial body of literature suggests the presence of an inflammatory process in parkinsonian state (Whitton, 2007), changes in pro-inflammatory cytokines in the gut were assessed using a cytokine microarray. It has been found in this work that groups with a combined dopaminergic and noradrenergic lesion have a significant increase in both expressions of IL-13 and VEGF. IL-6 also shows a decrease in treatment groups; however this decrease did not reach statistical significance. The therapeutic value of Exendin-4 (EX-4) was evaluated. It has been previously demonstrated that EX-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is neuroprotective in rodent models of PD (Harkavyi et al., 2008). In this thesis it has been found that EX-4 was able to reverse a decrease in gut contractility obtained through intracerebral bilateral 6-OHDA injection. Although more studies are required, EX-4 could be used as a possible therapy for the GI symptoms prominent in the early stages of PD.

Exporting a model of integrated disease management: A cross-case study analysis and application to Associação Protectora dos Diabéticos de Portugal

Although literature is lacking in the topic of internationalization of services, we manage to apply both the Uppsala model and the Eclectic Theory to the healthcare service. A cross-case study analysis with three international hospitals is done in order to define an internationalization pattern and conditions for a successful process. This is then applied to Associação Protectora dos Diabéticos de Portugal with the purpose of defining an internationalization strategy to the Association.

Ethical leadership and unethical pro-organizational behavior: A moderated mediation model of affective commitment and authenticity at work

Recently, unethical conduct in the workplace has been a focus of literature and media. Unethical pro-organizational behavior (UPB) refers to unethical conduct that employees engage in to benefit the organization. Given the complexity of UPB, there is an increasing need to understand how and under what conditions this attitude originates within organizations. Based on a sample of 167 employees and seven organizations, results support the moderated mediation model. An ethical leader increases employees’ organizational affective commitment which increases the likelihood to engage in UPB. However, the indirect relationship diminishes when employees feel authentic at work.

Psychometric properties of the Psychopathy Checklist : Youth version among portuguese juvenile delinquents

The main aim of the present study was to examine some psychometric properties of the Psychopathy Checklist: Youth Version (PCL:YV) among Portuguese juvenile delinquents. With forensic sample of 192 incarcerated male participants, the Portuguese version of the PCL:YV demonstrated promising psychometric properties of the three-factor model of youth psychopathy, internal consistency, convergent validity, concurrent validity, and retrospective validity that generally justify its use among Portuguese youths. Statistically significant associations were found with age of criminal onset, frequency of crimes, number of victims, and use of physical violence.

Appreciating the power of words and imaginative organizing: A triadic model of ethics practiced in everyday conversations

This thesis provides an alternative framework to analyze power and ethics practiced in everyday conversations, which constitute processes of organizing. Drawing upon narrative frameworks, the analyses of messages posted on an online message board demonstrate people’s imaginative capacity to create relevant stories, in respect of their precise grasp of factual understandings, contextual relevance and evaluative/moral appropriateness, by appropriating others’ words. Based on the empirical analyses, the thesis indicates that studies on power and ethics in organizations can be re-oriented towards appreciating irremediable power imbalances by offering alternative ways of member’s denoting experiences of power.

Heart hypoplasia in an animal model of congenital diaphragmatic hernia

PURPOSE: In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits. METHODS: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time - 31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies. RESULTS: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness. CONCLUSION: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1) than in Sh8 (100.8 ± 1.3), but comparable between aortocaval fistula 4 (50.0 ± 8.9) and Sh4 (84.8 ± 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P <.001), whereas left ventricular systolic pressure (r² = 0.73, P = .004) and end-diastolic pressure (r² = 0.55, P = 012) correlated positively and independently with interstitial fibrosis. CONCLUSION: Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.

Sonae MC: The road model of Kaizen

Sonae MC is considered the first success case of Kaizen in the retail industry. Before becoming a true role model for so many companies, there was a long road to walk. However, it may still be hard to understand the steps taken on the way. How could a training program develop into an integral continuous improvement system, and how did it affect the company – its people, culture, operations and strategy? How was it possible to get everyone on board? How could it be sustained until today, when Kaizen usually fails in the West? What were the critical factors for success?