Chronic Pruritus

O Prurido crónico é um sintoma que tem um impacto significativo na qualidade de vida dos doentes. Pode estar associado a um vasto conjunto de doenças e na maioria dos casos, é difícil conseguir um alívio completo da sintomatologia. A investigação da sua etiologia implica a colheita de uma história clínica meticulosa, bem com a realização do exame objectivo e de exames complementares de diagnóstico. O tratamento do prurido é frequentemente um desafio para o dermatologista e pode incluir a implementação de diferentes terapêuticas. Esta revisão pretende dar ênfase à abordagem clínica e às opções terapêuticas do doente com prurido crónico

The influence of planning and response inhibition on cognitive functioning of Non-Psychotic unipolar depressed suicide attempters

Depression is one of the main risk factors for suicide. However, little is known about the intricate relationships among depressive symptomatology in unipolar depression, suicide risk, and the characteristics of executive dysfunction in depressed patients. We compared 20 non-psychotic unipolar depressed suicide attempters to 20 matching depressed non-attempters and to 20 healthy controls to further investigate the possible differences in neuropsychological performance. Depressed subjects were controlled for current suicidal ideation, and their neuropsychological profile was assessed using a range of measures of executive functioning, attention, verbal memory, processing speed, and psychomotor speed. Depressed groups were outperformed by healthy controls. Depressed attempters presented more cognitive impairment than depressed non-attempters on a simple Go/No-go response inhibition task and performed better than non-attempters on the Tower of London planning task. Depressed attempters were clearly distinguished by a deficit in response inhibition (Go/No-go commission errors). The normative planning performance (Tower of London extra moves) of the suicide attempters was unexpected, and this unanticipated finding calls for further research. Normative planning may indicate an increased risk of suicidal behavior.info:eu-repo/semantics/publishedVersio

Revisiting the genetics of APOE

Apolipoprotein E (APOE) is a lipid-transport protein expressed in almost all tissues, including the brain. In addition to lipid delivery, brain APOE also regulates amyloid beta clearance and aggregation. In humans, there are three main isoforms, APOE2, APOE3 and APOE4, with structural differences that influence protein function. APOE4 is the most important genetic risk factor for Alzheimer’s disease and Dementia with Lewy bodies. In this review, we will focus on the genetic variability of APOE and its association with different diseases (mainly neurodegenerative, psychiatric and lipid-related). Despite the increasing number of studies, the association of APOE genetic variants with other neurological conditions beyond Alzheimer’s disease and Dementia with Lewy bodies is still far from clear. We will also discuss the association of different structural and functional aspects of APOE with different diseases, particularly the amyloid beta-dependent and-independent mechanisms, such as tau-mediated neurodegeneration, associated with Alzheimer’s disease pathogenesis. As the most significant genetic risk factor for Alzheimer’s disease, APOE has a central role in the risk assessment of this disease. Consequently, a better understanding of the impact of common and rare APOE variants will not only contribute to a more accurate risk management of these patients, but it will also clarify the potential of APOE as a therapeutic target

The Portuguese model of determinants that make up the management consultancy sector

In a historical retrospective, and although the literature entitles the management consultancy industry as an extraordinary industry and a unique phenomenon in the business context, these statements are not accompanied by a number of academic studies that highlight the importance of the effective work of management consultants. To battle the lack of studies in this emerging field, this article aims to build a determinant model that helps to understand this specific sector. The results of empirical analysis in the form of semi-structured interviews and questionnaires given to management consultants and managers of SMEs in Portugal, show that the activity of strategic consultants, mediated by strategic practices, bring in fact to the research of the strategy-as-practice a new direction in strategic thinking. It shows that consultant sector could be viewed as a key factor in the development of knowledge between different sectors in organizations, a Knowledge Intensive Activity, a specialist sector having consultants with the title of specialists and, consultants that could be considered as practical strategists.info:eu-repo/semantics/acceptedVersio

Drug Allergy with Cutaneous Manifestations. Diagnostic Approach

As reacções adversas a fármacos (RAF) representam um problema frequente na prática clínica. A alergia a fármacos resulta de mecanismos de hipersensibilidade imunológica e representa 6-10% do total de RAF. Clinicamente, as reacções alérgicas a fármacos podem ser classificadas como imediatas (tipo I) ou não-imediatas (com manifestações clínicas diversas e associadas sobretudo a reacções de tipo IV). Neste artigo são abordados aspectos gerais, nomeadamente os mecanismos imunopatogénicos implicados na alergia a fármacos e reactividade cruzada mas também as manifestações cutâneas mais relevantes, nomeadamente exantemas máculo-papulares, eritema fixo a fármacos (EFF), pustulose exantemática aguda generalizada (PEAG), síndrome de hipersensibilidade a fármacos (DRESS – drug rash with eosinophilia and systemic symptoms), síndrome de Stevens-Johnson/necrólise epidérmica tóxica (SSJ/NET). O papel dos testes cutâneos (epicutâneos ou intradérmicos de leitura tardia) na abordagem de reacções não-imediatas é também revisto. Os beta-lactâmicos (BL) são o grupo farmacológico mais frequentemente envolvido em reacções de hipersensibilidade imunológica e que mais dificuldades coloca na prática clínica diária, nomeadamente devido aos riscos de reactividade cruzada, pelo que é analisado em maior detalhe ao longo da revisão. A indução de tolerância a fármacos poderá ser considerada em casos selecionados, sobretudo quando na ausência de alternativas terapêuticas igualmente eficazes ou seguras

Neurohormonal modulation: The new paradigm of pharmacological treatment of heart failure

The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants.info:eu-repo/semantics/publishedVersio

Wind power forecasting with machine learning: single and combined methods

In Portugal, wind power represents one of the largest renewable sources of energy in the national energy mix. The investment in wind power started several decades ago and is still on the roadmap of political and industrial players. One example is that by 2030 it is estimated that wind power is going to represent up to 35% of renewable energy production in Portugal. With the growth of the installed wind capacity, the development of methods to forecast the amount of energy generated becomes increasingly necessary. Historically, Numerical Weather Prediction (NWP) models were used. However, forecasting accuracy depends on many variables such as on-site conditions, surrounding terrain relief, local meteorology, etc. Thus, it becomes a challenge to obtain improved results using such methods. This article aims to report the development of a machine learning pipeline with the objective of improving the forecasting capability of the NWP’s to obtain an error lower than 10%.info:eu-repo/semantics/publishedVersio

Novel mag variant causes cerebellar ataxia with oculomotor apraxia: Molecular basis and expanded clinical phenotype

Homozygous variants in MAG, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of hereditary spastic paraplegia (HSP). MAG is a glycoprotein member of the immunoglobulin superfamily, expressed by myelination cells. In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cerebellar ataxia with neuropathy and oculomotor apraxia. We used homozygosity mapping and exome sequencing to identify the MAG variant, and cellular studies to confirm its detrimental effect. Our results showed that this variant reduces protein stability and impairs the post-translational processing (N-linked glycosylation) and subcellular localization of MAG, thereby associating a loss of protein function with the phenotype. Therefore, MAG variants should be considered in the diagnosis of hereditary cerebellar ataxia with oculomotor apraxia, in addition to spastic paraplegia.This work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project UIDB/04293/2020. It was also funded by FEDER funds through the Programa Operacional Factores de Competitividade—COMPETE 2020 and by Nacional funds through the FCT [COMPETE: POCI-01-0145-FEDER-007440]. This work was also funded in part by the FCT grant FCT-ANR/BEX-GMG/0008/2013 and the Porto Neurosciences and Neurologic Disease Research Initiative at the i3S (Norte-01-0145-FEDER-000008), supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, also through FEDER. The authors also acknowledge the support of the i3S Scientific Platform Advanced Light Microscopy, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122) and GenomePT (POCI-01-0145-FEDER-022184). MS was the recipient of a fellowship (SFRH/BPD/116046/2016) from the FCT supported by POPH/MCTES funding