Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

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

What makes an entrepreneur?: The role of feelings

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

Web-assisted tobacco intervention in Portuguese : intentions to make behavioural changes and behavioural changes

ABSTRACT - The problem of how to support “intentions to make behavioural changes” (IBC) and “behaviour changes” (BC) in smoking cessation when there is a scarcity of resources is a pressing issue in public health terms. The present research focuses on the use of information and communications technologies and their role in smoking cessation. It is developed in Portugal after the ratification of WHO Framework Convention on Tobacco Control (on 8 November 2005). The prevalence of smokers over fifteen years of age within the population stood at 20.9% (30.9% for men and 11.8% for women). While the strategy of helping people to quit smoking has been emphasised at National Health Service (NHS) level, the uptake of cessation assistance has exceeded the capacity of the service. This induced the search of new theoretical and practical venues to offer alternative options to people willing to stop smoking. Among these, the National Health Plan (NHP) of Portugal (2004-2010), identifies the use of information technologies in smoking cessation. eHealth and the importance of health literacy as a means of empowering people to make behavioural changes is recurrently considered an option worth investigating. The overall objective of this research is to understand, in the Portuguese context, the use of the Internet to help people to stop smoking. Research questions consider factors that may contribute to “intentions to make behavioural changes” (IBC) and “behavioural changes” (BC) while using a Web-Assisted Tobacco Intervention Probe (WATIP). Also consideration is given to the trade-off on the use of the Web as a tool for smoking cessation: can it reach a vast number of people for a small cost (efficiency) demonstrating to work in the domain of smoking cessation (efficacy)”? In addition to the introduction, there is a second chapter in which the use of tobacco is discussed as a public health menace. The health gains achieved by stopping smoking and the means of quitting are also examined, as is the use of the Internet in smoking cessation. Then, several research issues are introduced. These include background theory and the theoretical framework for the Sense of Coherence. The research model is also discussed. A presentation of the methods, materials and of the Web-Assisted Tobacco Intervention Probe (WATIP) follows. In chapter four the results of the use of the Web-Assisted Tobacco Intervention Probe (WATIP) are presented. This study is divided into two sections. The first describes results related to quality control in relation to the Web-Assisted Tobacco Intervention Probe (WATIP) and gives an overview of its users. Of these, 3,150 answered initial eligibility questions. In the end, 1,463 met all eligibility requirements, completed intake, decided on a day to quit smoking (Dday) and declared their “intentions to make behavioural changes” (IBC) while a second targeted group of 650 did not decide on a Dday. With two quit attempts made before joining the platform, most of the participants had experienced past failures while wanting to stop. The smoking rate averaged 21 cigarettes per day. With a mean age of 35, of the participants 55% were males. Among several other considerations, gender and the Sense of Coherence (SOC) influenced the success of participants in their IBC and endeavour to set quit dates. The results of comparing males and females showed that, for current smokers, establishing a Dday was related to gender differences, not favouring males (OR=0.76, p<0.005). Belonging to higher Socio-economic strata (SES) was associated with the intention to consider IBC (when compared to lower SES condition) (OR=1.57, p<0.001) and higher number of school years (OR=0.70, p<0.005) favoured the decision to smoking cessation. Those who demonstrated higher confidence in their likelihood of success in stopping in the shortest time had a higher rate of setting a Dday (OR=0.51, p<0.001). There were differences between groups in IBC reflecting the high and low levels of the SOC score (OR=1.43, p=0.006), as those who considered setting a Dday had higher levels of SOC. After adjusting for all variables, stages of readiness to change and SOC were kept in the model. This is the first Arm of this research where the focus is a discussion of the system’s implications for the participants’ “intentions to make behavioural changes” (IBC). Moreover, a second section of this study (second Arm) offers input collected from 77 in-depth interviews with the Web-Assisted Tobacco Intervention Probe (WATIP) users. Here, “Behaviour Change” (BC) and the usability of the platform are explored a year after IBC was declared. A percentage of 32.9% of self-reported, 12-month quitters in continuous abstinence from smoking from Dday to the 12-month follow- up point of the use of the Web-Assisted Tobacco Intervention Probe (WATIP) has been assessed. Comparing the Sense of Coherence (SOC) scores of participants by their respective means, according to the two groups, there was a significant difference in these scores of non smokers (BC) (M=144,66, SD=22,52) and Sense of Coherence (SOC) of smokers (noBC) (M=131,51, SD=21,43) p=0.014. This WATIP strategy and its contents benefit from the strengthening of the smoker’s sense of coherence (SOC), so that the person’s progress towards a life without tobacco may be experienced as comprehensible, manageable and meaningful. In this sample the sense of coherence (SOC) effect is moderate although it is associated with the day to quit smoking (Dday). Some of the limitations of this research have to do with self-selection bias, sample size (power) and self-reporting (no biochemical validation). The enrolment of participants was therefore not representative of the smoking population. It is not possible to verify the Web-Assisted Tobacco Intervention Probe (WATIP) evaluation of external validity; consequently, the results obtained cannot be applied generalized. No participation bias is provided. Another limitation of this study is the associated limitations of interviews. Interviewees’ perception that fabricating answers could benefit them more than telling the simple truth in response to questions is a risk that is not evaluated (with no external validation like measuring participants’ carbon monoxide levels). What emerges in this analysis is the relevance of the process that leads to the establishment of the quit day (Dday) to stop using tobacco. In addition, technological issues, when tailoring is the focus, are key elements for scrutiny. The high number of dropouts of users of the web platform mandates future research that should concentrate on the matters of the user-centred design of portals. The focus on gains in health through patient-centred care needs more research, so that technology usability be considered within the context of best practices in smoking cessation.

Valuation of marine and coastal ecosystems: The role of ecological-economic modeling

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

Analyzing the impact of HRM Systems on the organizational climate, culture and outcomes: The mediating role of HMR Strength, organizational climate and culture

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

Uncovering the role of IFNAR1 in Experimental Cerebral malaria

Dissertation presented the Ph.D degree in Biology

The role of Grainy head in epithelial tissue growth

Part of the results of this thesis was presented in the following meetings: Susana Ponte, Lara Carvalho, Inês Cristo and António Jacinto. The role of Grainy head in epithelial tissue growth. Drostuga 2013. Faro, Portugal, January 3rd 2014 [poster] Susana Ponte, Lara Carvalho, Inês Cristo and António Jacinto. The role of Grainy head in epithelial tissue growth. Drostuga 2014. Tomar, Portugal, September 5th-6th 2014 [poster]

Storage of water molecules into biomimetic heterostructures: the role of roughness

The development of devices based on heterostructured thin films of biomolecules conveys a huge contribution on biomedical field. However, to achieve high efficiency of these devices, the storage of water molecules into these heterostructures, in order to maintain the biological molecules hydrated, is mandatory. Such hydrated environment may be achieved with lipids molecules which have the ability to rearrange spontaneously into vesicles creating a stable barrier between two aqueous compartments. Yet it is necessary to find conditions that lead to the immobilization of whole vesicles on the heterostructures. In this work, the conditions that govern the deposition of open and closed liposomes of 1.2-dipalmitoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (sodium Salt) (DPPG) onto polyelectrolytes cushions prepared by the layer-by-layer (LbL) method were analyzed. Electronic transitions of DPPG molecules as well as absorption coefficients were obtained by vacuum ultraviolet spectroscopy, while the elemental composition of the heterostructures was characterized by x-ray photoelectron spectroscopy (XPS). The presence of water molecules in the films was inferred by XPS and infrared spectroscopy. Quartz crystal microbalance (QCM) data analysis allowed to conclude that, in certain cases, the DPPG adsorbed amount is dependent of the bilayers number already adsorbed. Moreover, the adsorption kinetics curves of both adsorbed amount and surface roughness allowed to determine the kinetics parameters that are related with adsorption processes namely, electrostatic forces, liposomes diffusion and lipids re-organization on surface. Scaling exponents attained from atomic force microscopy images statistical analysis demonstrate that DPPG vesicles adsorption mechanism is ruled by the diffusion Villain model confirming that adsorption is governed by electrostatic forces. The power spectral density treatment enabled a thorough description of the accessible surface of the samples as well as of its inner structural properties. These outcomes proved that surface roughness influences the adsorption of DPPG liposomes onto surfaces covered by a polyelectrolyte layer. Thus, low roughness was shown to induce liposome rupture creating a lipid bilayer while high roughness allows the adsorption of whole liposomes. In addition, the fraction of open liposomes calculated from the normalized maximum adsorbed amounts decreases with the cushion roughness increase, allowing us to conclude that the surface roughness is a crucial variable that governs the adsorption of open or whole liposomes. This conclusion is fundamental for the development of well-designed sensors based on functional biomolecules incorporated in liposomes. Indeed, LbL films composed of polyelectrolytes and liposomes with and without melanin encapsulated were successfully applied to sensors of olive oil.

The role of qualitative data and systems thinking in addressing service decline in market towns

Retail services are a main contributor to municipal budget and are an activity that affects perceived quality-of-life, especially for those with mobility difficulties (e.g. the elderly, low income citizens). However, there is evidence of a decline in some of the services market towns provide to their citizens. In market towns, this decline has been reported all over the western world, from North America to Australia. The aim of this research was to understand retail decline and enlighten on some ways of addressing this decline, using a case study, Thornbury, a small town in the Southwest of England. Data collected came from two participatory approaches: photo-surveys and multicriteria mapping. The interpretation of data came from using participants as analysts, but also, using systems thinking (systems diagramming and social trap theory) for theory building. This research moves away from mainstream economic and town planning perspectives by making use of different methods and concepts used in anthropology and visual sociology (photo-surveys), decision-making and ecological economics (multicriteria mapping and social trap theory). In sum, this research has experimented with different methods, out of their context, to analyse retail decline in a small town. This research developed a conceptual model for retail decline and identified the existence of conflicting goals and interests and their implications for retail decline, as well as causes for these. Most of the potential causes have had little attention in the literature. This research also identified that some of the measures commonly used for dealing with retail decline may be contributing to the causes of retail decline itself. Additionally, this research reviewed some of the measures that can be used to deal with retail decline, implications for policy-making and reflected on the use of the data collection and analysis methods in the context of small to medium towns.

The role of Hedgehog signaling during zebrafish larvae fin fold regeneration

Several studies have demonstrated that although the structure of the adult and larval zebrafish caudal fin is different, there are similarities at the cellular and molecular level that turn larval zebrafish fin fold a useful model to study the basic principles of regeneration. In this process, while the essential role for Hedgehog (Hh) signaling is well established in the adult zebrafish caudal fin system, its involvement in juvenile tissue regeneration is still unknown. The aim of this Master thesis was therefore to evaluate the contribution of the Hh signaling pathway to the larval zebrafish fin fold regeneration process. Accordingly, we analyzed the expression of several Hh signaling components through in situ hybridization. Here, we showed that several of these genes are effectively expressed in the larval regenerating fin tissue, suggesting a role for Hh signaling also during larval regeneration. However, divergence in the regulation of few Hh signaling components appears to exist between the adult and larval zebrafish fin regeneration processes. Nevertheless, similarly to adult caudal fin regeneration, when Hh signaling was blocked, by using cyclopamine, the larval fin fold regenerative outgrowth is severely impaired. Since larval zebrafish fin fold is ciliated, and primary cilia are closely related to Hh signaling regulation in vertebrate systems, we further addressed the role of primary cilia during larval fin fold regeneration process. To this end, we used the zebrafish iguana mutant, in which primary cilia are not formed, to study the modulation of Hh signaling expression during larval fin fold regeneration in the absence of primary cilia. Here, we found that several genes were expressed with a delay, coincident with the delay in the mutant fin fold regeneration observed in previous work. We show that Hh signaling in the fin fold is crucial to promote cell proliferation. When Hh signaling is blocked using cyclopamine there is a strong blockage of cell proliferation and regeneration is also blocked. Surprisingly, in iguana mutants where Hh signaling is impaired but not totally blocked, cell proliferation is not detected but regeneration still occurs. This raises the question about the requirement of cell proliferation in larvae fin fold regeneration. By blocking the cell cycle using aphidicolin we demonstrate that cell proliferation is not necessary for zebrafish larvae fin fold regeneration.

What makes an entrepreneur? The role of feelings

This study uses a sample of 678 observations from the Community Innovation Survey 6 (CIS6) plus the Leadership Module attached in Portugal wherein 55.93% of the respondents are business Owners. It focuses on recent literature on Entrepreneurship to understand how the perceived importance of Personality Traits and Social Ties influence the decision-making process of the Entrepreneur towards an Intuitive or an Analytical Approach. It gets statistical significant values for the Founder/Sample in the traits, and for strong ties in the Founder/Owner Model shows statistical significance.

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

Assessing the role of social networks on migrant labor market outcomes: Evidence from a representative immigrant survey

What role do social networks play in determining migrant labor market outcomes? We examine this question using data from a random sample of 1500 immigrants living in Ireland. We propose a theoretical model formally predicting that immigrants with more contacts have additional access to job offers, and are therefore better able to become employed and choose higher paid jobs. Our empirical analysis confirms these findings, while focusing more generally on the relationship between migrants’ social networks and a variety of labor market outcomes (namely wages, employment, occupational choice and job security), contrary to the literature. We find evidence that having one more contact in the network is associated with an increase of 11pp in the probability of being employed and with an increase of about 100 euros in the average salary. However, our data is not suggestive of a network size effect on occupational choice and job security. Our findings are robust to sample selection and other endogeneity concerns.

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.