Nato after the Brussels Summit. An optimistic perspective

This paper aims at analyzing the results of the NATO Summit held in Brussels between 11 and 12 July 2018 by focusing on three major subjects, all of which are at the heart of the Alliance's concerns: first, NATO relations with Russia; second, the Alliance's defence and deterrence posture to face challenges and threats, whether on its eastern or southern flank; and finally, NATO relations with the European Union (EU). Following the annexation of Crimea by Russia in 2014, relations with the Alliance and even political dialogue have deteriorated significantly, driving the Alliance to adopt a new defence and deterrence posture. Also, in the South, NATO faces several challenges and threats, having to adapt its defence and deterrence posture to another context. The NATO-EU partnership continues to be strategic for strengthening defence in the European continent but also for cementing transatlantic relations, and it is imperative for the strength of this relationship to fulfill the burden-sharing commitments by increasing the European Allies defence budgets.Este ensaio inicia-se com uma caracterização do atual ambiente de segurança no espaço Euro-Atlântico para posteriormente tratar de analisar alguns dos resultados da Cimeira NATO realizada em Bruxelas entre 11 e 12 de julho de 2018. Essa análise centra-se em três grandes áreas, todas elas no centro das preocupações da Aliança. São elas: as relações com a Rússia; a postura de defesa e dissuasão da Aliança para fazer face aos desafio e ameaças que enfrenta, quer no seu flanco Este, quer a Sul; e por fim as Relações com a União Europeia. Após a anexação da Crimeia pela Rússia em 2014, as relações com a Aliança e mesmo o diálogo político deterioraram-se significativamente, tendo como consequência a adoção de uma nova postura de defesa e dissuasão da Aliança. Também a Sul a NATO enfrenta diversos desafios e ameaças, tendo de adaptar a sua postura de defesa e dissuasão a este contexto. A parceria NATO-UE continua a ser estratégica para o fortalecimento da defesa no continente europeu mas também para cimentar as relações transatlânticas, sendo imperioso para a solidez dessa relação o cumprir dos compromissos de partilha do fardo incrementando os aliados europeus os seus orçamentos de defesa.info:eu-repo/semantics/publishedVersio

Gold nanoprobes for the detection of mutations associated with antibiotic resistance in Mycobacterium tuberculosis complex

Dissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaTuberculosis is still one of the leading human infectious diseases, with 8.7 million new cases reported in 2011 alone. Also, the increasing rate of multidrug-resistant tuberculosis (MDR-TB) and its treatment difficulties pose a serious public health threat especially in developing countries. Resistance to isoniazid and rifampicin, first line antibiotics, is commonly associated with point mutations in katG, inhA and rpoB genes of Mycobacterium tuberculosis complex (MTBC). Therefore, the development of a cheap, fast and simple molecular method to assess susceptibility profiles would have a huge impact in the capacity of early diagnosis and treatment of MDR-TB patients. Gold nanoparticles functionalised with thiol-modified oligonucleotides (Au-nanoprobes) have shown the potential to provide a rapid and sensitive detection method for MTBC and single base mutations associated with antibiotic resistance, namely the characterisation of the three most relevant codons in rpoB gene associated to rifampicin resistance. In this work the Au-nanoprobe approach is extended towards the discrimination of specific mutations within inhA gene which is associated with resistance to isoniazid. Using a multiplex PCR reaction for rpoB and inhA genes, it was possible to assess both loci in parallel, and extend the potential of the Au-nanoprobe method to MDR-TB molecular characterisation with special application in the most frequent genotypes circulating in the Lisbon Health Region

Gold Nanoparticles to Tackle Drug Resistance in Cancer

The most common type of cancer treatment, chemotherapy, often fails due to the acquisition of resistance. It is therefore of the utmost importance to better understand the cellular mechanisms of resistance, while developing new strategies to tackle drug resistance. Nanomedicine promises to develop new tools for diagnosing and treating of diseases, improving human health. This thesis explored five main strategies to overcome drug resistance in cancer cells: i) new anti-cancer compounds, ii) nanovectorisation and targeting of compounds, iii) gold nanoparticles (AuNP) for hyperthermia and combination with chemotherapy iv) AuNP assisted angiogenesis arrest with laser ablation and chemotherapy v) AuNP mediated gene silencing of efflux pumps. We started by characterizing the mechanism of action of a new anti-tumour compound (ZnD), that was able to reduce the viability of a colon cancer cell line (HCT116 DR) resistant to doxorubicin (DOX), a first-line chemotherapeutic. We vectorized our compound with AuNP, resulting in increased toxicity to HCT116 DR mouse xenografts. Taking advantage of the photothermal properties of AuNP, we combined chemotherapy with photo hyperthermia by irradiating AuNP with a green laser. Hyperthermia was especially effective against HCT116 DR. Since angiogenesis is a milestone in cancer development, we aimed to prevent it, using an anti-angiogenic peptide vectorized with AuNP and laser irradiation, resulting in a vascularization reduction of 91% in vivo. We have observed that ABCB1 efflux pump was the major cause of resistance of DOX resist cell line, therefore we silenced its mRNA with an anti-sense oligonucleotide AuNP. Our results showed that although the silencing was effective, cells did not return to a sensitive phenotype, requiring further experiments. Altogether this thesis shows the potential of nanotechnology for cancer treatment, both in chemotherapy and in surgery, where green lasers are already used. This work can be applied to drug resistant tumours, increasing the efficacy of treatment

Cost-Effectiveness of Rosuvastatin in the Prevention of Ischemic Heart Disease in Portugal

AbstractObjectiveTo assess the cost-effectiveness of rosuvastatin in the treatment of hypercholesterolemia and the prevention of ischemic heart disease (IHD) in Portugal.MethodsA probabilistic Markov model was constructed to analyze the costs and consequences of lifetime treatment with rosuvastatin, atorvastatin, pravastatin, and simvastatin. For this purpose, the results from randomized head-to-head trials evaluating low-density lipoprotein (LDL) changes were combined with the results from a meta-analysis defining the relationship between LDL levels and fatal and nonfatal IHD events. The incidence of myocardial infarction (MI) was derived from a 9-year Portuguese observational study. The eligible population was defined as untreated individuals aged more than 35 years with LDL levels above 115 mg/dl. Death rates due to IHD and other causes were obtained from official data. Resource use in the treatment of MI was estimated by a Delphi panel of eight Portuguese cardiologists with at least 15 years of clinical practice. Costs were calculated from the payers' perspective.ResultsRosuvastatin increases life expectancy between 5.5 and 12.1 days per patient. It is cost-saving when compared to atorvastatin, but it increases costs when assessed against pravastatin and simvastatin (€1,004 and €684 per patient, respectively). Therefore, rosuvastatin is a dominant alternative compared to atorvastatin, having an incremental cost-effectiveness ratio of €30,350 to pravastatin and €39,340 to simvastatin. In the probabilistic sensitivity analysis, performed rosuvastatin always dominates atorvastatin and is associated with a cost per life-year gained inferior to €50,000 in 95.7% of the cases when compared to pravastatin and in 67.0% simulations when assessed against simvastatin.ConclusionsRosuvastatin is a cost-effective alternative in the prevention of IHD in Portugal

ANTIAGREGANTES E ANTICOAGULANTES EM CIRURGIA DERMATOLÓGICA – NORMAS DE ORIENTAÇÃO CLÍNICA

Introduction: Management of antithrombotic therapy is not a consensual topic in the field of dermatologic surgery. Skin surgeons must weigh the risk of bleeding against the thrombotic risk when deciding how to manage those drugs in the perioperative setting. Material and Methods: The authors reviewed the literature in order to provide clinical practice guidelines for the management of these patients.Results: There are few significant studies published in this area, and sometimes presenting different approaches and recommendations. The main objective for the dermatologic surgeon should be to optimize surgical outcomes without forgetting the thrombotic and hemorrhagic risks inherent to the patient and the surgical procedure.Conclusions: We recommend the continuation of antithrombotics during low bleeding risk surgery. In patients with high thromboembolic risk we recommend the continuation of antithrombotic drugs in low bleeding risk surgeries, and its eventual suspension with bridging in high bleeding risk surgeries. However, these global recommendations should not outweigh an individualized approach of each particular patient.Introdução: A abordagem da terapêutica antitrombótica não é consensual na cirurgia dermatológica. O dermatologista tem de ponderar entre o risco hemorrágico e o risco trombótico quando decide do manuseio destes fármacos no período perioperatório. Material e Métodos: Os autores reviram a literatura disponível com o intuito de elaborar normas de orientação clínica para a abordagem destes doentes.Resultados: Há poucos estudos significativos publicados nesta área, e por vezes com diferentes abordagens e recomendações. O principal objetivo do cirurgião dermatológico deverá ser a otimização dos resultados cirúrgicos sem esquecer os riscos trombóticos e hemorrágicos inerentes ao doente e ao procedimento cirúrgico. Conclusões: Recomendamos a continuação dos antitrombóticos nos procedimentos dermatológicos com baixo risco hemorrágico. Nos doentes com elevado risco tromboembólico recomendamos a continuação do fármaco antitrombótico nos procedimentos de baixo risco hemorrágico, e a ponderação da sua suspensão com substituição por heparina de baixo peso molecular nos procedimentos de elevado risco hemorrágico. No entanto, estas recomendações globais não se devem sobrepor a uma abordagem individualizada à situação clínica pontual de cada doente

Electrocoagulação com Cateter Venoso Periférico no Tratamento de Lagos Venosos

Venous lakes comprise vascular ectasias of the upper dermis, usually seen in the lips of older patients. Treatment can be sought for cosmetic or functional reasons and therapeutic options include laser ablation, cryotherapy or surgery. Electrosurgery is a frequent and efficacious method in the resolution of venous lakes, although possibly damaging to the adjacent skin. In order to minimize skin damage, an intravenous catheter can be used to deliver electrocoagulation intralesionally from an electroscalpel, being described as an improvement of the classic procedure. The authors describe this modified electrosurgical technique as a safe, simple and readily-accessible therapeutic option in the treatment of venous lakes.Lagos venosos são ectasias vasculares da derme superior localizados predominantemente nos lábios de indivíduos idosos. O seu tratamento pode ser desejável por motivos cosméticos ou funcionais, existindo uma miríade de métodos terapêuticos possíveis, incluindo ablação com laser, crioterapia ou cirurgia. A electrocoagulação é também um método eficaz, mas pode condicionar morbilidade do tecido são adjacente. Para minorar este dano, o recurso ao cateter venoso periférico para condução da energia até ao tecido alvo tem sido descrito como uma modificação vantajosa à técnica clássica. Os autores descrevem o recurso à electrocoagulação com auxílio de cateter venoso periférico como alternativa acessível, simples e segura na abordagem dos lagos venosos

Position Paper - Os Desafios da Reavaliação de Tecnologias de Saúde em Portugal

Introduction: The recently created Health Technology Assessment System (SiNATS) in Portugal will allow the reassessment of health technologies in a clinical practice context. This position paper intends to list and briefly describe the numerous challenges and limitations that may influence the premises and the Outcomes of the health technology reassessments and therefore its own purpose. This paper reflects the position adopted by the ISPOR Portugal Regional Chapter (International Society for Pharmacoeconomics and Outcomes Research – ISPOR Portugal) regarding this subject. Methods: A group of members of ISPOR Portugal reviewed the literature available, namely documents of international workgroups that have previously focused on similar matters, and conducted a critical analysis on the challenges faced by health technologies reassessment within the national context. A final revision of the paper was requested to all members of the ISPOR Portugal Regional Chapter. Results: Several limitations that may potentially compromise the reassessment of health technologies have been identified and thoroughly described, namely those with regard to the intervention itself (i.e. the health technology), the study population, the selection of the comparator and the Health Outcomes to consider in this type of analysis. The relevance of the information sources on which the investigation of comparative effectiveness may rely upon (at least to some extent) as well as the limitations and flaws inherent to it (i.e. bias and confounding factors) were also highlighted. Conclusions: A health technology reassessment system must be subject to an a priori analysis regarding its potentialities and limitations. In this paper these issues are addressed while taking SiNATS’s goals as reference points. Nevertheless, it is necessary to give continuity to this work, particularly through the creation of workgroups whose purpose is to study and analyse with greater detail the matters mentioned herein. Such work may, in fact, prove to be crucial for a successful implementation of a reassessment system that makes fair and efficient decisions on the funding of health technologies in Portugal

Karapandzic Flap, a Possible Solution to a Case of Advanced Squamous Cell Carcinoma of the Lip

O carcinoma espinhocelular cutâneo é uma neoplasia cutânea não melanocítica, potencialmente fatal, que resulta da proliferação descontrolada dos queratinócitos. Predominante na cabeça e pescoço, esta surge preferencialmente em zonas expostas ao sol. O diagnóstico tem por base a apresentação clínica da lesão, corroborado com o auxílio da dermatoscopia, necessitando, porém, da confirmação histológica.Este trabalho reporta o caso de um homem de 71 anos referenciado por lesão do lábio inferior, hiperqueratósica e infiltrativa, sugestiva de carcinoma espinhocelular cutâneo. Confirmado a suspeita procedeu-se à excisão radical da lesão, cujo defeito resultante ocupava 70% do comprimento do lábio inferior na sua porção mediana, em espessura total, tendo-se recorrido à reconstrução com recurso aos retalhos de deslizamento e rotação descritos por Karapandzic. O resultado final caracterizou-se por cicatrizes a preencherem os sulcos fisiológicos e pela manutenção da continência oral, bem como da sensibilidade e mobilidade labiais.Cutaneous squamous cell carcinoma is a potentially fatal non-melanocytic skin cancer, which results from the uncontrolled proliferation of keratinocytes. Predominant in the head and neck, it’s intimately connected to sun exposed areas. The diagnosis is based on the clinical presentation of the lesion, supported with the assistance of dermoscopy, needing, however, histological confirmation.This paper reports the case of a 71 year old male evaluated for a hyperkeratotic and infiltrative lower lip injury, suggestive of squamous cell carcinoma. After confirming the suspicion we proceeded with the radical excision of the lesion, whose resulting defect occupied 70% of the lower lip length in its middle portion, reaching its total thickness, and immediate reconstruction using Karapandzic’s sliding and rotating flap technique. The end result was characterized by scarring concealed in the physiological grooves and the maintenance of oral continence as well as the sensitivity and lip mobility

Pedómetro como ferramenta laboratorial: uma abordagem no contexto da Educação Física

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Gemcitabine-Induced Bullous Acral Erythema

O eritema acral da quimioterapia é caracterizado por áreas eritematosas e dolorosas, envolvendo predominantemente as mãos e pés, com formação de bolhas em casos severos. A gemcitabina é responsável frequentemente por reacções adversas cutâneas, embora estas sejam habitualmente transitórias e ligeiras. Relatamos o caso de um doente sob quimioterapia paliativa com gemcitabina por adenocarcinoma ductal pancreático, que desenvolveu lesões bolhosas em ambos os pés, de maiores dimensões à esquerda. A histopatologia foi consistente com eritema acral. A variante bolhosa do eritema acral da quimioterapia é uma reacção rara e, embora descrita para agentes citotóxicos estruturalmente semelhantes, não tem sido associada à gemcitabina. No doente apresentado, os antecedentes pessoais de doença arterial periférica podem ter desempenhado um papel importante na apresentação clínica final.Chemotherapy-induced acral erythema is characterized by areas of painful erythema affecting predominantly hands and feet, and in severe cases bullous lesions may develop. Gemcitabine is frequently responsible for cutaneous side effects, but these are usually mild and transient. We report a patient under palliative chemotherapy for pancreatic ductal adenocarcinoma with gemcitabine, who presented large bullous lesions on both feet, but of larger size on the left. Histopathology was consistent with acral erythema. The bullous variant of chemotherapy-induced acral eythema is a rare reaction, and although described for structurally similar cytotoxic agents, it has not been reported in association with gemcitabine. In our case, the patient’s medical history of significant peripheral arterial disease may have also played an important role in the overall clinical presentation