Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity

INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77% and 46%, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4%) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.

Dynamics of Capillaria-hepatica-induced hepatic septal fibrosis in rats

INTRODUCTION: The pathogenesis of septal hepatic fibrosis, induced in rats by Capillaria hepatica infection, was studied with the aid of a large collection of stored paraffin blocks, representative of the different evolutive phases of fibrosis which appeared in 100% of infected rats. METHODS: Studies were conducted involving histology, immunohistochemistry, immunofluorescence and morphometric methods, in order to observe the dynamic behavior of the cellular and matrix components of fibrosis, over a one year period of evolution. RESULTS: Observation verified that septal fibrosis originates from several portal spaces simultaneously. Its origin and progression involve blood vessel proliferation (angiogenesis), multiplication of actin-positive cells (pericytes and myofibroblasts) and progressive collagen deposition. By the end of 4-5 months, a progressive decrease in all these components was observed, when signs of regression of septal fibrosis became more evident over time. CONCLUSIONS: Besides indicating the fundamental role played by angiogenesis in the pathogenesis of fibrosis, these morphological data concerning the dynamics of this C. hepatica experimental model proved to be adequate for future investigations regarding the functional aspects of fibrosis induction, progression and regression.

Information provision improvement with a geofencing event-bases system

Nowadays there is a big percentage of the population, specially young users, which are smartphone users and there is a lot of information to be provided within the applications, information provision should be done carefully and should be accurate, otherwise an overload of information will be produced, and the user will discard the app which is providing the information. Mobile devices are becoming smarter and provide many ways to filter information. However, there are alternatives to improve information provision from the side of the application. Some examples are, taking into account the local time, considering the battery level before doing an action and checking the user location to send personalized information attached to that location. SmartCampus and SmartCities are becoming a reality and they have more and more data integrated every day. With all this amount of data it is crucial to decide when and where is the user going to receive a notification with new information. Geofencing is a technique which allows applications to deliver information in a more useful way, in the right time and in the right place. It consists of geofences, physical regions delimited by boundaries, and devices that are eligible to receive the information assigned to the geofence. When devices cross one of these geofences an alert is pushed to the mobile device with the information.

Characterization of molecular damage induced by UV photons and carbon ions on biomimetic heterostructures

The study of the effect of radiation on living tissues is a rather complex task to address mainly because they are made of a set of complex functional biological structures and interfaces. Particularly if one is looking for where damage is taking place in a first stage and what are the underlying reaction mechanisms. In this work a new approach is addressed to study the effect of radiation by making use of well identified molecular hetero-structures samples which mimic the biological environment. These were obtained by assembling onto a solid support deoxyribonucleic acid (DNA) and phospholipids together with a soft water-containing polyelectrolyte precursor in layered structures and by producing lipid layers at liquid/air interface with DNA as subphase. The effects of both ultraviolet (UV) radiation and carbon ions beams were systematically investigated in these heterostructures, namely damage on DNA by means vacuum ultraviolet (VUV), infrared (IR), X-Ray Photoelectron (XPS) and impedance spectroscopy. Experimental results revealed that UV affects furanose, PO2-, thymines, cytosines and adenines groups. The XPS spectrometry carried out on the samples allowed validate the VUV and IR results and to conclude that ionized phosphate groups, surrounded by the sodium counterions, congregate hydration water molecules which play a role of UV protection. The ac electrical conductivity measurements revealed that the DNA electrical conduction is arising from DNA chain electron hopping between base-pairs and phosphate groups, with the hopping distance equal to the distance between DNA base-pairs and is strongly dependent on UV radiation exposure, due loss of phosphate groups. Characterization of DNA samples exposed to a 4 keV C3+ ions beam revealed also carbon-oxygen bonds break, phosphate groups damage and formation of new species. Results from radiation induced damage carried out on biomimetic heterostructures having different compositions revealed that damage is dependent on sample composition, with respect to functional targeted groups and extent of damage. Conversely, LbL films of 1,2-dipalmitoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (Sodium Salt) (DPPG) liposomes, alternated with poly(allylamine hydrochloride) (PAH) revealed to be unaffected, even by prolonged UV irradiation exposure, in the absence of water molecules. However, DPPG molecules were damaged by the UV radiation in presence of water with cleavage of C-O, C=O and –PO2- bonds. Finally, the study of DNA interaction with the ionic lipids at liquid/air interfaces revealed that electrical charge of the lipid influences the interaction of phospholipid with DNA. In the presence of DNA in the subphase, the effects from UV irrladiation were seen to be smaller, which means that ionic products from biomolecules degradation stabilize the intact DPPG molecules. This mechanism may explain why UV irradiation does not cause immediate cell collapse, thus providing time for the cellular machinery to repair elements damaged by UV.

Numerical prediction of diffusion and electric field-induced iron nanoparticle transport

Zero valent iron nanoparticles (nZVI) are considered very promising for the remediation of contaminated soils and groundwaters. However, an important issue related to their limited mobility remains unsolved. Direct current can be used to enhance the nanoparticles transport, based on the same principles of electrokinetic remediation. In this work, a generalized physicochemical model was developed and solved numerically to describe the nZVI transport through porous media under electric field, and with different electrolytes (with different ionic strengths). The model consists of the Nernst–Planck coupled system of equations, which accounts for the mass balance of ionic species in a fluid medium, when both the diffusion and electromigration of the ions are considered. The diffusion and electrophoretic transport of the negatively charged nZVI particles were also considered in the system. The contribution of electroosmotic flow to the overall mass transport was included in the model for all cases. The nZVI effective mobility values in the porous medium are very low (10−7–10−4 cm2 V−1 s−1), due to the counterbalance between the positive electroosmotic flow and the electrophoretic transport of the negatively charged nanoparticles. The higher the nZVI concentration is in the matrix, the higher the aggregation; therefore, low concentration of nZVI suspensions must be used for successful field application.

Marketing plan: How to benefit from the European population ageing and attract the affluent senior segment to choose Lisbon as a tourism destination?

NSBE - UNL

S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions

INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99% of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75%). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.

How to increase and attract more tourists into Kenya throught experiental marketing

This marketing plan project is a culmination of extensive strategies with the use of experiential marketing to address issues confronting the Kenyan tourism industry in order to have a sustainable tourism sector. Following the terrorist attack carried out by Islamist militants’ belonging to al-Shabaab terrorist organization on Nairobi’s Westgate shopping mall in September 2013, tourist forecast has gone down sharply with an average of 20% fall in tourists’ arrivals which is likely to have an impact on the tourism sector in Kenya. Even before the deadly attack on Westgate, the most lethal attack by Islamist terrorists in 15 years in Kenya, the government through the Kenya tourist board had announced that in 2013 tourist arrivals were down by 12%, at 495,978, according to an October 2013 report by Bloomberg. Tourism revenues were also down by 7.4%, over FY12/13 (July-June) to reach KES96.24bn, according to a September 2013 report on the local Capital FM website. Beyond 2013, much will depend on how quickly the Kenya tourist board can regain control of the situation. The Kenyan government believes that the Westgate mall attack was a 'one-off' incident, with a low probability of a similar event happening again over the short term period. Germany, United States, United Kingdom, Australia, Italy, France and Canada continue to be the key source market however; the Kenya tourist board can make continued growth stronger from new emerging markets in order to increase new arrivals into the country. The marketing plan outlines the objectives to be implemented and provides the implementation strategy, activity plans, monitoring and evaluation plans, financial requirements projections and proposes a new structure of experiential marketing. A number of regional forces are identified that will impact tourism into the country including global, social and economic forces, emerging trends in visitor motivations and behavior, emerging forces in experiential marketing. A major component of the strategy identifies target markets for Kenya to commensurate with the level of resources that will be available for marketing and promotion, in keeping with the forces and trends identified and the nature of the Kenya tourism environment. The agreed upon target market segments are: generic/mass travel, experiential travel, creative travel, adventure seeking travel, senior/extended/long stay travel, and business related travel. The strategy phases the development of the target markets over the years of the marketing strategies in order to yield the best opportunity for results. A core activity in developing a marketing strategy is determining the nature of experiences Kenya offers in tourism. The strategy’s experience development process will continue to develop within the context of the products identified which will be promoted regionally: culture/heritage, nature, community-based. Each county in the country has a significant number of attractions and experiences and the challenge of the country is to bring these together in a creative and innovative way in order to encourage tourists to visit more than one county in Kenya.

Charming Estoril B&B: business plan tourism

UNL - NSBE

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

Introduction The progression of human papillomavirus (HPV) infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR) is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment. Methods We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes. Results We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8%) was predominant in samples with ≥1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all samples. Conclusions The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.

Turning Lisbon into a tourism and luxury shopping destination for Chinese travellers

Branding Lab

How to take advantage of wine tourism: Creation of a new concept for central Alentejo based on its potential and worldwide success factors

Wine Tourism is gaining importance in today’s world and more destinations and establishments have been arising. After understanding the importance of this economic activity and the factors it must have to succeed, a new project was conceived for Central Alentejo taking into account its potential. This project is an example of how to take advantage of Wine Tourism in wine regions that are underexplored, such as Aldeias de Montoito, the village near Redondo to which a Business Plan will be created, explaining the strategies to pursue in order to have a successful Wine Tourism destination.

Low cost carriers: The case of Oporto Airport and its touristic impact in the region

Both Oporto and the North Region of Portugal definitions of tourism have evolved significantly during the past decade. In this journey it is relevant to highlight the contribution of the arrival of Low Cost Carriers (LCCs) at Francisco Sá Carneiro Airport, thus contributing to a rapid expansion of this region as a tourism destination. Hence, this work project aims to understand the touristic and economic impact motivated by the entry of LCCs in Oporto and in the North Region of Portugal and tries to understand if this event was in fact an asset in the development of the aforementioned tourism destinations.

Cruise tourism in Lisbon - Cruise tourism activity and its impact on the city

Field lab: Tourism