Study of the risk factors related to acquisition of urinary tract infections in patients submitted to renal transplant

INTRODUCTION: Urinary tract infections (UTI) among transplant recipients are usually caused by gram-negative microorganisms and can provoke a high incidence of morbidity and mortality. The aim of this study was to evaluate the risk factors associated with the acquisition of UTIs during the first year after renal transplantation. METHODS: Here, we report a single-center retrospective cohort study of 99 renal transplant patients followed for the first year after surgery. The definition of a UTI episode was a urine culture showing bacterial growth and leucocyturia when patients presented with urinary symptoms. The absence of infection (asymptomatic bacteriuria) was defined as an absence of symptoms with negative urine culture or bacterial growth with any number of colonies. RESULTS: Ninety-nine patients were included in the study. During the study, 1,847 urine cultures were collected, and 320 (17.3%) tested positive for bacterial growth. Twenty-six (26.2%) patients developed a UTI. The most frequent microorganisms isolated from patients with UTIs were Klebsiella pneumoniae (36%), with 33% of the strains resistant to carbapenems, followed by Escherichia coli (20%). There were no deaths or graft losses associated with UTI episodes. CONCLUSIONS: Among the UTI risk factors studied, the only one that was associated with a higher incidence of infection was female sex. Moreover, the identification of drug-resistant strains is worrisome, as these infections have become widespread globally and represent a challenge in the control and management of infections, especially in solid organ transplantation.

Novel antibiotic-loaded orthopaedic bone cements: insights on drug release profiles and biocompatibility

Acrylic bone cement (BC) is widely used as an anchor of artificial joints. Bacterial infection due to biofilm formation and inflammation are common and difficult to treat problems associated with commercial available BC formulations. Research on novel BC compositions is urgently needed. The main objective of this thesis was to develop a new biocompatible antibiotic-loaded BC with improved release profile. To achieve that aim several additives were incorporated, as an antibiotic (levofloxacin) to combat bacterial growth, an anti-inflammatory drug (diclofenac) to decrease the inflammatory process and two well-known and broadly used biopolymers, alginate and chitosan in order to increase matrix porosity, and in this way to intensify the amount of released drug. Novel BC formulations were tested in order to find the most suitable one that had potential to proceed to clinical application. Numerous tests were conducted as: a) evaluation of drug release profiles in different biomimetic media, b) mechanical and surface studies, c) microbiological activity testing against Staphylococcus aureus and d) in vitro biocompatibility assays (fibroblasts and osteoblasts). In general, the addition of biopolymers increased drug release, didn’t compromised BC mechanical properties and increased BC hydrophilicity. Microbiological testing revealed that Lev[BC]Chi was the only matrix that reduced significantly biofilm formation. On the contrary, alginate and diclofenac loading into BC seemed to increase biofilm growth. Biocompatibility studies showed some decrease in cell viability, in particularly on osteoblasts, mainly due to the high amounts of released drugs. In conclusion, the present work has shown that the matrix with more potential to proceed in further investigations was Lev[BC]Chi. Other conditions (namely additives and drugs concentrations) should be evaluated with the other tested BC matrices before being discharged.

Nanomedicines, a strategy to evade multidrug resistance

Multidrug resistance is a major problems associated with cancer chemotherapy. Efflux transports is one of the numerous mechanisms involved in multidrug resistance. P-glycoprotein is a transmembrane protein, responsible for drug efflux, which decreases drugs intracellular bioavailability, consequently decreasing their efficacy against cancer. Cancer growth and dissemination depends on the expression of transcriptional factors such as, Twist. Among other features, this protein is related with cells chemoresistance possible by regulation of multidrug resistance pathways including the P-glycoprotein expression. The herein study proposes to demonstrate if paclitaxel entrapped nanoparticles is an effective system in evading multidrug resistance mechanisms and if functionalization of a specific antibody against cancer stem cells receptors (anti-CD44v6) has the capability to target selectively these cells increasing nanoparticles efficacy. Therefore solid lipid nanoparticles were prepared and a breast cancer cell line (MDA-MB-436) was exposed to them in order to assess unloaded nanoparticles cytotoxic effects, increased pharmacologic efficacy of loaded nanoparticles relative to the free drug and their ability to evade multidrug resistance. The proposed solid lipid nanoparticles system proved to be capable of efficiently evading multidrug resistance mechanisms; however no improvement was added when these nanoparticles were functionalized with the antibody in the in vitro studies. However, the nanoparticles system is effective against multidrug resistance mechanisms.

Nurses' training on dealing with alcohol and drug abuse: a question of necessity

The purpose of this article is to present a brief review on the need for changes in nurses' undergraduate education concerning alcohol and drugs. Specialized literature makes it clear that nurses have difficulties giving care to psychoactive substance users as part of their functions in the various health care sites. This may be associated with a deficiency in formal education. In the face of the social importance concerning these related questions in the scope of research, care, and education, we made an attempt at deepening the study on this theme, which could contribute to changes in practice, care, and undergraduate nursing education.

Contribution to drug discovery and development for tauopathies using yeast as a model

This work aimed to contribute to drug discovery and development (DDD) for tauopathies, while expanding our knowledge on this group of neurodegenerative disorders, including Alzheimer’s disease (AD). Using yeast, a recognized model for neurodegeneration studies, useful models were produced for the study of tau interaction with beta-amyloid (Aβ), both AD hallmark proteins. The characterization of these models suggests that these proteins co-localize and that Aβ1-42, which is toxic to yeast, is involved in tau40 phosphorylation (Ser396/404) via the GSK-3β yeast orthologue, whereas tau seems to facilitate Aβ1-42 oligomerization. The mapping of tau’s interactome in yeast, achieved with a tau toxicity enhancer screen using the yeast deletion collection, provided a novel framework, composed of 31 genes, to identify new mechanisms associated with tau pathology, as well as to identify new drug targets or biomarkers. This genomic screen also allowed to select the yeast strain mir1Δ-tau40 for development of a new GPSD2TM drug discovery screening system. A library of unique 138 marine bacteria extracts, obtained from the Mid-Atlantic Ridge hydrothermal vents, was screened with mir1Δ-tau40. Three extracts were identified as suppressors of tau toxicity and constitute good starting points for DDD programs. mir1Δ strain was sensitive to tau toxicity, relating tau pathology with mitochondrial function. SLC25A3, the human homologue of MIR1, codes for the mitochondrial phosphate carrier protein (PiC). Resorting to iRNA, SLC25A3 expression was silenced in human neuroglioma cells, as a first step towards the engineering of a neural model for replicating the results obtained in yeast. This model is essential to understand the mechanisms of tau toxicity at the mitochondrial level and to validate PiC as a relevant drug target. The set of DDD tools here presented will foster the development of innovative and efficacious therapies, urgently needed to cope with tau-related disorders of high human and social-economic impact.

The impact of poor power quality in solar photovoltaic microgeneration: technical problems and losses of revenue

This paper presents a critical and quantitative analysis of the influence of the Power Quality in grid connected solar photovoltaic microgeneration installations. First are introduced the main regulations and legislation related with the solar photovoltaic microgeneration, in Portugal and Europe. Next are presented Power Quality monitoring results obtained from two residential solar photovoltaic installations located in the north of Portugal, and is explained how the Power Quality events affect the operation of these installations. Afterwards, it is described a methodology to estimate the energy production losses and the impact in the revenue caused by the abnormal operation of the electrical installation. This is done by comparing the amount of energy that was injected into the power grid with the theoretical value of energy that could be injected in normal conditions. The performed analysis shows that Power Quality severally affects the solar photovoltaic installations operation. The losses of revenue in the two monitored installations M1 and M2 are estimated in about 27% and 22%, respectively.

Project management: evaluation of the problems in the portuguese construction industry

During recent decades it has been possible to identify several problems in construction industry project management, related with to systematic failures in terms of fulfilling its schedule, cost and quality targets, which highlight a need for an evaluation of the factors that may cause these failures. Therefore, it is important to understand how project managers plan the projects, so that the performance and the results can be improved. However, it is important to understand if other areas beyond cost and time management that are mentioned on several studies as the most critical areas, receive the necessary attention from construction project managers. Despite the cost and time are the most sensitive areas/fields, there are several other factors that may lead to project failure. This study aims at understand the reasons that may cause the deviation in terms of cost, time and quality, from the project management point of view, looking at the knowledge areas mentioned by PMI (Project Management Institute).

Benefits from energy related building renovation beyond costs, energy and emissions

The relevance of the building sector in the global energy use as well as in the global carbon emissions, both in the developed and developing countries, makes the improvement of the overall energy performance of existing buildings an important part of the actions to mitigate climate changes. Regardless of this potential for energy and emissions saving, large scale building renovation has been found hard to trigger, mainly because present standards are mainly focused on new buildings, not responding effectively to the numerous technical, functional and economic constraints of the existing ones. One of the common problems in the assessment of building renovation scenarios is that only energy savings and costs are normally considered, despite the fact that it has been long recognized that investment on energy efficiency and low carbon technologies yield several benefits beyond the value of saved energy which can be as important as the energy cost savings process. Based on the analysis of significant literature and several case studies, the relevance of co-benefits achieved in the renovation process is highlighted. These benefits can be felt at the building level by the owner or user (like increased user comfort, fewer problems with building physics, improved aesthetics) and should therefore be considered in the definition of the renovation measures, but also at the level of the society as a whole (like health effects, job creation, energy security, impact on climate change), and from this perspective, policy makers must be aware of the possible crossed impacts among different areas of the society for the development of public policies.

Cinco para ouvir: discursos de ex-reclusos/as sobre a Prisão

Dissertação de mestrado integrado em Psicologia

Pró-fármacos fotoativáveis do péptido AAPV: síntese e avaliação da libertação controlada por luz

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

Emotional and behavioral problems in preschoolers: risk factors and assessment Issues

Tese de Doutoramento em Psicologia Aplicada.

Five-year evolution of drug prescribing in a university adult intensive care unit

Introduction: Drug prescription is difficult in ICUs as prescribers are many, drugs expensive and decisions complex. In our ICU, specialist clinicians (SC) are entitled to prescribe a list of specific drugs, negotiated with intensive care physicians (ICP). The objective of this investigation was to assess the 5-year evolution of quantity and costs of drug prescription in our adult ICU and identify the relative costs generated by ICP or SC. Methods: Quantities and costs of drugs delivered on a quarterly basis to the adult ICU of our hospital between 2004 and 2008 were extracted from the pharmacy database by ATC code, an international five-level classification system. Within each ATC first level, drugs with either high level of consumption, high costs or large variations in quantities and costs were singled out and split by type of prescriber, ICP or SC. Cost figures used were drug purchase prices by the hospital pharmacy. Results: Over the 5-year period, both quantities and costs of drugs increased, following a nonsteady, nonparallel pattern. Four ATC codes accounted for 80% of both quantities and costs, with ATC code B (blood and haematopoietic organs) amounting to 63% in quantities and 41% in costs, followed by ATC code J (systemic anti-infective, 20% of the costs), ATC code N (nervous system, 11% of the costs) and ATC code C (cardiovascular system, 8% of the costs). Prescription by SC amounted to 1% in drug quantities, but 19% in drug costs. The rate of increase in quantities and costs was seven times larger for ICP than for SC (Figure 1 overleaf ). Some peak values in costs and quantities were related to a very limited number of patients. Conclusions: A 5-year increase in quantities and costs of drug prescription in an ICU is a matter of concern. Rather unexpectedly, total costs and cost increases were generated mainly by ICP. A careful follow-up is necessary to try influencing this evolution through an institutional policy co-opted by all professional categories involved in the process.

T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.