Novas abordagens da estimulação cerebral profunda

Trabalho final de mestrado integrado em Medicina (Neurocirurgia), apresentado à Faculdade de Medicina da Universidade de Coimbra.Contextualização: As origens da técnica implicada na Estimulação Cerebral Profunda (ECP) estão fortemente ligadas à descoberta dos efeitos da estimulação elétrica de áreas cerebrais profundas realizadas durante neurocirurgias funcionais estereostáticas lesionais. O seu objetivo consiste em reequilibrar circuitos neuronais danificados, cujas alterações determinam défices neurológicos ou comportamentais. Trata-se de uma técnica de modulação, não lesiva e reversível, isto é, todo o dispositivo pode ser desligado sem cirurgia adicional ou mesmo removido. Desde a década de 1990 que se tem vindo a renovar o interesse na ECP e a sua técnica tem sido melhorada e considerada uma ferramenta neuromodulatória clínica muito poderosa. Atualmente, há uma utilização muito abrangente da ECP no tratamento, não só de perturbações do movimento incluindo o tremor associado à Doença de Parkinson (DP) e distonia, como também numa panóplia de outras patologias que suscitam interesse, nomeadamente Depressão major, Demência (Doença de Alzheimer (DA)), Distúrbios da Consciência, Distúrbios Alimentares (Anorexia Nervosa (AN) e Obesidade) e Comportamento Aditivo. Objetivos: Analisar a evolução crescente da técnica em novas indicações e caracterizar a sua origem teórica e base experimental. Destacando o enquadramento presente da ECP, torna-se, ainda, fundamental referir os seus imensos benefícios no controlo eficaz de sintomas incapacitantes refratários a terapêutica médica (e cirúrgica), bem como alertar para as preocupações e limitações aquando da realização dos ensaios clínicos e efeitos adversos deste tratamento cirúrgico. Material e Métodos: Com o intuito de investigar esta temática, procedeu-se à revisão da literatura publicada, recorrendo para tal à base de dados PUBMED. Inicialmente foram recolhidos artigos de 2009 a 2014, utilizando as palavras-chave Deep brain stimulation, cruzando-a com cada uma das vertentes do tema do trabalho. Foram, ainda, utilizados artigos referenciados bibliograficamente pelos artigos originalmente escolhidos, mesmo datados anteriormente relativamente à pesquisa inicial. Encontram-se incluídos artigos de revisão, artigos originais, ensaios clínicos e debates. Foi, também, recolhida bibliografia referente a revistas indexadas na área da Neurocirurgia desde 2009 até a atualidade. Resultados: Foi realizada uma avaliação e seleção rigorosa dos artigos mais relevantes com o intuito de fornecer informação mais completa sobre o tema deste trabalho e aprofundar a metodologia dos estudos publicados. Devido aos inúmeros artigos recolhidos a partir da pesquisa realizada, tornou-se fundamentar abordar os principais estudos efetuados em cada subtema por ordem cronológica para uma melhor compreensão e validação dos mesmos. Conclusão: No que diz respeito à aplicação da ECP, esta técnica em si tem uma ampla margem de progressão. Se considerarmos a multiplicidade de circuitos neuronais do cérebro que podem ser modulados através de impulsos elétricos, assim como a interpretação e a compreensão crescentes desses circuitos, percebemos que, esta técnica se torna numa alternativa mais eficaz e segura relativamente à cirurgia lesional, ainda que seja necessário um conhecimento mais profundo e preciso da técnica e rigor na escolha de “alvos terapêuticos” ótimos.Background: The origins of Deep Brain Stimulation (DBS) are strongly linked to the discovery of electrical stimulation effects on deep brain areas performed during lesional stereotactic functional neurosurgery. Its aim is to rebalance damaged neural circuits, whose changes determine neurological or behavioral deficits. This is a non-injurious and reversible technique, since the entire device can be turned off without additional surgery or removed. There has been renewed interest in DBS since 1990 and its technique has been improved and considered a very powerful neuromodulatory clinical tool. Currently, there is a very comprehensive use of DBS in the treatment, not only for movement disorders including tremor associated with Parkinson's disease (PD) and dystonia as well as a host of other conditions including major Depression, Dementia (Alzheimer's Disease (AD)), Disorders of Consciousness, Eating Disorders (Anorexia Nervosa (AN) and Obesity) and Addictive Behavior. Objectives: To analyze the increasing evolution of the technique in new indications and characterize its theoretical basis and experimental origin. Highlighting the present framework of the DBS, becomes essential to note their immense benefits in effective control of disabling symptoms refractory to medical (and surgical) therapy, and alert to possible side effects and to limitations affecting clinical trial development. Material and Methods: A review of the published literature, resorting to PUBMED, was performed. Initially, articles from 2009 to 2014 were collected using keywords Deep brain stimulation, crossing it with each of the aspects of the theme of the work. Additional references from initially surveyed papers were also added. Review articles, original articles, clinical trials and debates were included. Literature from peer reviewed was also collected in the field of neurosurgery from 2009 to the present. Results: A rigorous evaluation and selection of the most relevant articles in order to provide more complete information on the subject of this work and deepen the methodology of published studies was performed. Due to the numerous articles collected from the survey, it became base address key studies in each sub-theme in chronological order for better understanding and validation. Conclusion: With regard to DBS utilization, the technique itself has a wide margin for improvement. If we consider the multiplicity of brain circuits in the brain which can be modulated by electrical impulses, as well as the interpretation and growing understanding of these circuits, we realize that this technique is becoming a more effective and safer alternative, although more knowledge and rigorous technique are needed in order to choose optimal "therapeutic targets"

Anal canal adenocarcinoma locally treated with abdominoperineal resection after chemoradiotherapy: case report and review of literature

Background: Primary adenocarcinoma of the anal canal is rare, representing less than 20% of anal canal cancers. Given the limited data regarding treatment and outcomes, the management of this type of cancer is focused on a combined modality therapy involving radical surgery and neoadjuvant/adjuvant chemoradiotherapy. Case study: A 74-year-old woman presented with pruritus and anal pain with 6 months duration. MRI showed a semi-concentric mass in anal canal posterior wall. After an incisional biopsy that revealed an adenocarcinoma, the patient underwent neoadjuvant chemoradiotherapy followed by laparoscopic abdominoperineal resection. Conclusion: There is limited research into anal adenocarcinoma since the rarity of this condition. The prognosis of anal adenocarcinoma is poor and the management remains controversial. Therapy strategies are not well established, however, general agreement states that a combined multimodality (combination of radical surgical resection and pre or postoperative chemoradiotherapy) achieves the best outcome

Overexpression of tumour-associated carbohydrate antigen sialyl-Tn in advanced bladder tumours

Little is known on the expression of the tumour-associated carbohydrate antigen sialyl-Tn (STn), in bladder cancer. We report here that 75% of the high-grade bladder tumours, presenting elevated proliferation rates and high risk of recurrence/progression expressed STn. However, it was mainly found in non-proliferative areas of the tumour, namely in cells invading the basal and muscle layers. STn was also found in tumour-adjacent mucosa, which suggests its dependence on a field effect of the tumour. Furthermore, it was not expressed by the normal urothelium, demonstrating the cancer-specific nature of this antigen. STn expression correlated with that of sialyltransferase ST6GalNAc.I, its major biosynthetic enzyme. The stable expression of ST6GalNAc.I in the bladder cancer cell line MCR induced STn expression and a concomitant increase of cell motility and invasive capability. Altogether, these results indicate for the first time a link between STn expression and malignancy in bladder cancer. Hence, therapies targeting STn may constitute new treatment approaches for these tumours

1,2,4-Trioxolane and 1,2,4,5-Tetraoxane endoperoxides against old-world Leishmania parasites: in vitro activity and mode of action

Leishmaniasis remains one of the ten Neglected Tropical Diseases with significant morbidity and mortality in humans. Current treatment of visceral leishmaniasis is difficult due to a lack of effective, non-toxic, and non-extensive medications. This study aimed to evaluate the selectivity of 12 synthetic endoperoxides (1,2,4-trioxolanes; 1,2,4,5-tetraoxanes) and uncover their biochemical effects on Leishmania parasites responsible for visceral leishmaniasis. The compounds were screened for in vitro activity against L. infantum and L. donovani and for cytotoxicity in two monocytic cell lines (J774A.1 and THP-1) using the methyl thiazol tetrazolium assay. Reactive oxygen species formation, apoptosis, and mitochondrial impairment were measured by flow cytometry. The compounds exhibited fair to moderate anti-proliferative activity against promastigotes of the 2 Leishmania species, with IC50 values ranging from 13.0 ± 1.7 µM to 793.0 ± 37.2 µM. Tetraoxanes LC132 and LC138 demonstrated good leishmanicidal activity on L. infantum amastigotes (IC50 13.2 ± 5.2 and 23.9 ± 2.7 µM) with low cytotoxicity in mammalian cells (SIs 22.1 and 118.6), indicating selectivity towards the parasite. Furthermore, LC138 was able to induce late apoptosis and dose-dependent oxidative stress without affecting mithocondria. Compounds LC132 and LC138 can be further explored as potential antileishmanial chemotypes.info:eu-repo/semantics/publishedVersio

O COMPORTAMENTO DA TAXA SELIC E AS OPERAÇÕES DE IN’VESTIMENTO E FINANCIAMENTO DE PESSOA FÍSICA NO PERÍODO PÓS-CRISE ECONÔMICA

A recente crise econômica enfrentada pelo Brasil, no período de 2014 a 2016, ocasionou, entre outras alterações, o aumento da taxa de juros e da inflação, afetando o mercado financeiro. Neste contexto, a presente pesquisa teve como objetivo identificar o comportamento da taxa Selic e a sua relação com a evolução dos investimentos e financiamentos pessoa física no período pós-crise econômica, em uma instituição financeira privada. O procedimento metodológico utilizado foi de natureza quantitativa e descritiva, dividida em duas etapas, primeiramente foi efetuada a análise de dados no panorama brasileiro das operações de crédito e investimentos pessoa física nas instituições bancárias privadas, utilizando informações do BACEN em três períodos: período anterior à crise econômica, P1 (2013), P2 período de crise econômica (2014 a 2015) e no período pós crise econômica P3 (2016 a 2017). A segunda etapa consistiu em realizar a análise dos investimentos e financiamentos de pessoa física de uma instituição financeira privada, comparando-os com o panorama nacional. Os resultados demonstraram que no período de crise, com a taxa Selic em alta, houve crescimento em algumas modalidades de investimentos e diminuição na concessão de financiamentos. Já no período pós-crise econômica, com a taxa Selic em baixa, os investimentos tiveram redução. A concessão de financiamentos, por sua vez, apresentou leve recuperação

Necrotizing Fasciitis Causing Acute Compartment Syndrome after Radial Artery Catheterization

Necrotizing fasciitis is a rare but potentially fatal infection involving the subcutaneous tissue and fascia with the development of necrosis of these structures. Acute compartment syndrome occurs when increased pressure within a closed muscle compartment compromises the circulation and function of the tissues within that space. We report the case of a male patient who was admitted to the intensive care unit for the management of urosepsis due to an acute obstructive pyelonephritis complicated by cardiopulmonary arrest. A radial arterial catheter in the left arm was urgently inserted, under suboptimal aseptic technique. His clinical condition progressively deteriorated, and swelling of the left arm with extension to the forearm with incipient signs of compromised perfusion were observed. The diagnosis of necrotizing fasciitis with acute compartment syndrome was made and an emergency fasciectomy performed. Following this, the patient gradually improved, organ dysfunction resolved, and he was discharged without sequelae

Tunable Perforated Panel Sound Absorbers for Variable Acoustics Room Design

Variable acoustics systems are promising engineering developments for multi-purpose rooms and workspaces in many buildings. However, due to space requirements associated with most of the tuning devices used for that purpose, these solutions are hardly adopted in practice. In this work, two innovative tunable sound absorbers that cope with this drawback are proposed, one consisting of rotating perforated panels and the other being a panel with an iris-type aperture. Compared with conventional perforated panel sound absorbers, the designed solutions yield a variable open area ratio system, whose configuration allows tuning the absorption bandwidth without misusing space. To assess their sound absorption coefficient, impedance tube experiments were carried out following the standardized method described in ISO 10534-2 over specimens fabricated for this purpose using laser cutting and additive manufacturing technology. The results not only show their good sound absorption performance but also highlight their tuning capabilities. Complementarily, a model based on the ray tracing method was developed to evaluate the performance of these solutions in a case study room, for different occupancy levels, with the results supporting the previous assertions and revealing the improved intelligibility features when used in such scenarios. The proposed solutions, together with the prediction model, provide a feasible approach for the design and development of tunable sound absorbers in variable room acoustics.This research was partially funded by FCT—Fundação para a Ciência e a Tecnologia, I.P., by Base Funding (UIDB/04029/2020, doi.org/10.54499/UIDB/04029/2020) and Programmatic Funding (UIDP/04029/2020) of the research unit “Institute for Sustainability and Innovation in Structural Engineering—ISISE”, and under the Associate Laboratory Advanced Production and Intelligent Systems ARISE, reference LA/P/0112/2020. This work was also financed by FEDER funds through the Competitivity Factors Operational Programme—COMPETE within the scope of the project ADJUST—Development of acoustic panels progressively adjustable with smart acting—SII & DT Project CENTRO-01-0247-FEDER-033884