Pé diabético: prevenção

Introdução: A identificação dos pacientes diabéticos em risco de desenvolver úlceras do pé, e a necessidade da implementação de medidas preventivas justifica-se pela frequência e gravidade das amputações que daí resultam e as suas consequências tanto a nível médico, social e económico. Objectivos: Revisão da eficácia de métodos dirigidos a prevenção de úlceras no pé diabético. Foi realizada uma pesquisa na base de dados da Medline/Pubmed e fontes documentais de referência. Não foram colocados limites temporais à pesquisa. Desenvolvimento: A prevenção de ulceração no pé diabético inicia-se pela pesquisa da neuropatia e baseia-se essencialmente no teste do Semmes-Weinstein monofilamento 10g, sendo a perda da sensibilidade termo-álgica o principal factor de risco. A doença vascular periférica associada a isquémia tecidular, é um factor agravante e deve ser estudada pela medição regular do índice tornozelo-braço, podendo necessitar de um estudo complementar pela determinação da pressão parcial de oxigénio transcutânea. Essas medidas juntamente com a elaboração de uma história clínica e de um exame físico minucioso na pesquisa de lesões pré-ulcerativas, completado pelo exame sistemático do calçado, permite aos profissionais de saúde estratificar o risco lesional e determinar qual o tipo de intervenção a por em prática. A graduação do risco faz-se em 4 graus. Os graus 2 e 3 justificam cuidados prioritários. As medidas interventivas passam essencialmente pela educação do paciente diabético, centrada na sensibilização do doente e familiares quanto a perda da sensibilidade termo-álgica e suas consequências e quais os cuidados de higiene a terem em conta. Outras medidas preventivas incluem a optimização do controlo glicémico e o tratamento de outros factores de risco cardiovasculares, cuidados podológicos nomeadamente o desbridamento de calos e tratamento de onicomicoses. Doentes com deformações dos pés apresentando evidências de grande pressão plantar beneficiam do uso de palmilhas e/ou calçado a medida. Casos seleccionados podem beneficiar de intervenções cirúrgicas. Conclusão: Realça-se a importância do rastreio de todos os pacientes diabéticos quanto ao risco de desenvolver lesões do pé. As medidas interventivas a serem postas em prática devem ser adaptadas ao risco lesional e ao paciente. Baseiam-se numa abordagem multidisciplinar sendo essencial a criação de consultas profilácticas nos cuidados de saúde primária, já incluídas no Programa Nacional de Prevenção e Controlo da Diabetes.Introduction: The identification of diabetic high-risk patients to develop a foot ulcer, and the implementation of means of prevention are justified by the frequency and gravity of the resulting amputations and their consequences on the medical, as well as social and economic levels. Objectives: To review the efficiency of the methods advocated for preventing diabetic foot ulcers. This study is based on searches from the data bank of Medline/Pubmed and standard reference texts, without any time limitation. Results: The prevention of the ulceration of a diabetic foot starts with a search for neuropathy, and is based essentially on the Semmes-Weinstein monofilament test while considering that the loss of protective sensation is the main risk factor. The peripheral vascular disease, associated with tissue ischemia, are aggravating factors and must be monitored using the ankle-brachial blood pressure index. This can be completed by determining the tanscutaneous oxygen tension. These results, combined with the compiling of a medical history and a thorough physical examination to search for pre-ulcerative lesions, enable clinicians to stratify patients based on risk and to determine the type of intervention. This graduation has four grades, with the second and third ones requiring priority care. The means of intervention consist mainly in education, by informing the diabetic patients and their families of the loss of the patient’s protective sensation, its consequences, but also informing them about proper foot care and periodic foot examinations. Additional prophylactic interventions include optimizing glycemic control, the treatment of other cardiovascular risk factors, and podiatric care such as debridement of calluses and onychomycosis. Patients with foot deformities that show evidence of high plantar pressure benefit from custom and/or therapeutic shoes. Certain cases can also be eligible for surgical interventions. Conclusion: This study showed the importance of a general screening of diabetic patients to identify those who risk developing foot lesions. The means of intervention to be put in practice must be adapted to the risks of ulceration, to the patients, and should be based on a multidisciplinary approach. The creation of prophylactic consultations in the primary care setting is already included in the Programa Nacional de Prevenção e Controlo da Diabetes

GPU ray casting

For many applications, such as walk-throughs or terrain visualization, drawing geometric primitives is the most efficient and effective way to represent the data. In contrast, other applications require the visualization of data that is inherently volumetric. For example, in biomedical imaging, it might be necessary to visualize 3D datasets obtained from CT or MRI scanners as a meaningful 2D image, in a process called volume rendering. As a result of the popularity and usefulness of volume data, a broad class of volume rendering techniques has emerged. Ray casting is one of these techniques. It allows for high quality volume rendering, but is a computationally expensive technique which, with current technology, lacks interactivity when visualizing large datasets, if processed on the CPU. The advent of efficient GPUs, available on almost every modern workstations, combined with their high degree of programmability opens up a wide field of new applications for the graphics cards. Ray casting is among these applications, exhibiting an intrinsic parallelism, in the form of completely independent light rays, which allows to take advantage of the massively parallel architecture of the GPU. This paper describes the implementation and analysis of a set of shaders which allow interactive volume rendering on the GPU by resorting to ray casting techniques

A Situação de paragem cardiorrespiratória: experiências dos enfermeiros

Dissertação de mestrado em Enfermagem Médico-Cirúrgica apresentada na Escola Superior de Saúde do Instituto Politécnico de Viana do CasteloA Paragem Cardiorrespiratória (PCR) é um evento que pode ocorrer em meio intra-hospitalar, normalmente de modo inesperado. Exige uma resposta imediata e eficiente o que gera nos profissionais de saúde, nomeadamente nos enfermeiros que na maior parte das vezes se encontram na primeira linha, stress e até dilemas éticos. Neste sentido, surge este estudo que visa compreender as experiências dos enfermeiros de uma unidade de internamento perante uma situação de PCR. Este assenta numa abordagem qualitativa, com caráter descritivo simples e exploratório, em que a estratégia de recolha de dados incidiu na entrevista semiestruturada, dirigida a oito enfermeiros. Os dados foram analisados com o recurso à técnica de análise de conteúdo. Dos dados sobressaem fatores que dificultam a atuação do enfermeiro perante a situação de PCR nomeadamente, a inexperiência do enfermeiro, o défice de conhecimentos relativos aos equipamentos e aos procedimentos, fatores relacionados com os recursos (humanos, materiais e condições físicas) e a tomada de decisão em reanimar ou não reanimar. O trabalho em equipa, a formação contínua e a partilha de experiências para reflectir sobre a situação e ajudar no alívio do stress, foram também os fatores facilitadores que emergiram no estudo. Foi visível também que a situação desencadeia diversos sentimentos nos enfermeiros, sentimentos positivos como a felicidade e a satisfação e sentimentos negativos como a angústia, a ansiedade, a frustração, a impotência, o medo e o stress. Esta dualidade de sentimentos surge da possibilidade de se conseguir salvar a vida da pessoa. Estes resultados sugerem que é importante implementar estratégias/dinâmicas favorecedoras de uma formação contínua e de partilha de experiências nas equipas que proporcionam uma melhor intervenção nestas situações.The Cardiopulmonary Arrest (CPA) is an event that can occur in a hospital environment, typically in an unexpected way. Requires an immediate response and efficient that generates in health professionals, especially nurses, most of whom are in the first line, stress and even ethical dilemmas. In this regard, this study aims to understand the experiences of nurses in a Nursing unit in a situation of CPA. This is based on a qualitative approach, with character simple descriptive and exploratory, in that the strategy of data collection focused on semi-structured interviews, addressed to eight nurses. The data were analyzed with the use of content analysis technique. The data stand out factors that hinder the action of the nurse in this situation of CPA in particular were the inexperience of the nurse, the lack of knowledge concerning the equipment and procedures, factors related to the resources (human, material and physical conditions) and the decision-making in resuscitate or do not resuscitate order. The teamwork, continuous training and the sharing of experiences to reflect on the situation and help to relieve stress, were also the facilitating factors that emerged in the study. It was visible that the CPA situation triggers various feelings in nurses, positive feelings, such as happiness and satisfaction and negative feelings such as fear, anxiety, frustration, helplessness, fear and stress. This duality of feelings comes from the possibility of being able to save person’s life. These results suggest that it is important to implement strategies/dynamic favoring a continuous training and sharing of experiences in the teams that provide a better intervention in these situations

A machine learning assessment of the two states model for lipid bilayer phase transitions

We have adapted a set of classification algorithms, also known as Machine Learning, to the identification of fluid and gel domains close to the main transition of dipalmitoyl-phosphatidylcholine (DPPC) bilayers. Using atomistic molecular dynamics conformations in the low and high temperature phases as learning sets, the algorithm was trained to categorize individual lipid configurations as fluid or gel, in relation with the usual two-states phenomenological description of the lipid melting transition. We demonstrate that our machine can learn and sort lipids according to their most likely state without prior assumption regarding the nature of the order parameter of the transition. Results from our machine learning approach provides strong support in favor of a two-states model approach of membrane fluidity

WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma

Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. Results: We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, glioma stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models, using both overexpressing and silencing models, WNT6 expression was associated with shorter overall survival, and increased features of tumor aggressiveness. Mechanistically, WNT6 contributes to activate typical oncogenic pathways, including Src and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6 as an independent prognostic biomarker of shorter survival in GBM patients from several independent cohorts. Conclusion: Our findings establish WNT6 as a novel oncogene in GBM, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.FCT - Foundation for Science and Technology (PTDC/SAU-GMG/113795/2009 and IF/00601/2012 to B.M.C.; SFRH/BD/92786/2013 to C.S.G.; SFRH/BD/88121/2012 to J.V.C.; SFRH/BD/81042/2011 to M.P.; SFRH/BD/93443/2013 to S.Q.) and Fundação Calouste Gulbenkian (B.M.C.), by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT under the project POCI-01-0145-FEDER-007038; by the project NORTE-01-0145-FEDER-000013 and NORTE-01-0246-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and by the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Impact of EGFR genetic variants on glioma risk and patient outcome

B.M. Costa and M. Viana-Pereira contributed equally to this work; The authors thank the Immunochemotherapy Department of Hospital S. Marcos, and Clinica Laboratorial Dr. Edgar Botelho Moniz, S. Tirso, Portugal, for their helpful assistance in the management of controlsBACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. METHODS: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. RESULTS: None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma. Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies.Schering-Plough Farma, PortugalFundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/33612/2009; SFRH/BD/29145/200

Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75ntr receptors? a study using 192 IgG-saporin lesions in rats

In previous studies electrically-evoked release of acetylcholine in septal slices was demonstrated. The present experiment aimed at verifying if this release involved intrinsic neurons bearing p75(NTR) receptors. Long-Evans rats sustained injections of 192 IgG-saporin into the medial septum/diagonal band of Broca (0.8 microg). Sham-operated rats served as controls. Two to 3.5 weeks later, the electrically-evoked release of acetylcholine ([(3)H]ACh) was measured in slices from the lateral septum (LS), medial septum (MS) and diagonal band of Broca (DBB). Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and monoamine concentrations were measured in the septum, cortex and hippocampus. The lesion extent was also assessed by ChAT immunostaining in a separate series of rats. In the septum, the number of ChAT-positive neurons was depleted dramatically (>90% at the level of the injection site). In the hippocampus, the lesions reduced ChAT and AChE activity by 91% and 84%, respectively. In the cortex, this reduction was weaker (-55% and -47%). In the septal region, the reduction was either weak or not significant. The evoked release of acetylcholine in septal slices was not reduced, except in the slices from the LS (-64%). The effects of physostigmine and atropine confirmed the presence of autoreceptors. Our data exclude that a major part of the acetylcholine released by MS and DBB slices derived from intrinsic neurons bearing p75(NTR) receptors. In the LS, part of the released acetylcholine might be from projections of such neurons located in the LS, MS and/or DBB. These data also suggest that the MS and the DBB may be the target of extrinsic cholinergic innervation that does not bear p75(NTR) receptors

HOXA9 promotes glioblastoma initiation, aggressiveness and resistance to therapy

Glioblastoma is the most common and malignant subtype of glioma, exhibiting remarkable resistance to treatment. Here we investigated the oncogenic potential of HOXA9 in gliomagenesis, the molecular and cellular mechanisms by which HOXA9 may render glioblastoma more aggressive, and how HOXA9 affects response to chemotherapy and prognosis. Expression microarrays were used to identify HOXA9 target genes. Stable glioblastoma cell lines with ectopic HOXA9 overexpression or shRNA-­mediated knockdown of HOXA9 were established to evaluate the roles of HOXA9 in cell viability, death, invasion, and response to temozolomide. Subcutaneous and orthotopic intracranial xenograft models of glioblastoma were established to evaluate the oncogenic potential of HOXA9 in vivo, and its role in response to temozolomide and overall survival. Transcriptomic analyses identified novel HOXA9-­target genes that have key roles in critical cancer processes, including cell proliferation, adhesion, DNA metabolism and repair, and stem cell maintenance. Functional assays with a variety of glioblastoma cells revealed that HOXA9 promotes cell viability, stemness, and invasion; conversely, HOXA9 displayed anti-­apoptotic functions. Additionally, ectopic expression of HOXA9 promoted the malignant transformation of human immortalized astrocytes in an intracranial orthotopic mouse model of glioblastoma, and caused tumor-­associated death. HOXA9 also mediated resistance to temozolomide treatment both in vitro and in vivo. Mechanistically, BCL2 was identified as a novel HOXA9 target that may be therapeutically targeted. Indeed, the pharmacological inhibition of BCL2 with ABT-­737 specifically reverted temozolomide resistance in HOXA9-­positive cells. These data establish HOXA9 as a critical driver of glioma initiation, aggressiveness and resistance to therapy

Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

Background: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. Methods: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. Results: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. Conclusion: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) grant ref. PTDC/SAU-FCF/104347/2008, under the scope of ‘Programa Operacional Temático Factores de Competitividade’ (COMPETE) of ‘Quadro Comunitário de Apoio III’ and co-financed by the Fundo Europeu De Desenvolvimento Regional (FEDER). Ricardo Amorim was recipient of the fellowship SFRH/BD/98002/2013, from Fundação para a Ciência e a Tecnologia (FCT Portugal).info:eu-repo/semantics/publishedVersio

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies