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Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz Introdução: A Periodontite é uma patologia inflamatória dos tecidos de suporte dentários. A sua etiologia é multifatorial, sendo a causa bacteriana apontada como primordial para o seu desenvolvimento. Recentemente, estudos demonstram que os vírus podem atuar como patógenos putativos desta doença. O objetivo da presente investigação prende-se com a avaliação da associação entre quatro vírus: Herpes Simples 1 e 2 (HSV1 e HSV2), Epstein-Barr (EBV) e Citomegalovírus (CMV) e a patologia periodontal. Materiais e Métodos: Um total de 100 pacientes, da Clínica Universitária Egas Moniz, foram incluídos no estudo, após assinatura de um consentimento informado. Dos 100 indivíduos, 50 apresentavam doença periodontal e 50 periodonto saudável. Amostras de fluído crevicular foram extraídas com auxílio de cones de papel previamente esterilizados e analisadas à posteriori. Procedeu-se primeiramente à extração de DNA e seguidamente ao teste PCR Multiplex (Polymerase Chain Reaction) para avaliar a presença dos vírus enunciados. Resultados: Foram detetados, em pacientes periodontalmente comprometidos, HSV1, HSV2, EBV e CMV (38%, 24%, 32% e 12% respetivamente, dos indivíduos possuíam estes vírus no fluído crevicular). No grupo saudável foram detetados HSV1, HSV2 e EBV em 2% dos indivíduos e em nenhum foi detetado CMV. Conclusão: Face aos resultados obtidos parece haver uma associação entre a presença de HSV1, HSV2, EBV e doença periodontal. Os vírus não são a etiologia primordial da Periodontite, no entanto, podem exercer um papel na mesma, contribuindo para a sua severidade e reativação, consequentemente o planeamento de uma terapêutica contra estes vírus pode auxiliar no tratamento periodontal. Introduction: Periodontitis is an inflammatory pathology of the tooth supporting tissues. Its etiology is multifactorial, however, the bacterial cause is considered as primordial for its development. Recently, studies have shown that viruses can act as putative pathogens of this disease. The goal of the present investigation is related to the evaluation of the association between four viruses: Herpes simplex 1 and 2 (HSV1 and HSV2), Epstein-Barr (EBV) and Cytomegalovirus (CMV) and periodontal pathology. Materials and methods: A total of 100 patients, from Clínica Universitária Egas Moniz, were enrolled in the study, by signing an informed consent. Of the 100 individuals, 50 had periodontal disease and 50 healthy periodontium. Samples of crevicular fluid were extracted with the aid of paper cones previously sterilized and analyzed retrospectively. DNA extraction was performed first and then the PCR Multiplex test (Polymerase Chain Reaction) to evaluate the presence of the viruses. Results: In patients, periodontally compromised, HSV1, HSV2, EBV and CMV (38%, 24%, 32% and 12% respectively, of the individuals had these viruses in the crevicular fluid). In the healthy group, HSV1, HSV2 and EBV were found in 2% of the individuals and in no cmv was found. Conclusion: In view of the results obtained there seems to be an association between the presence of HSV1, HSV2, EBV and periodontal disease. Viruses are not the primary etiology of Periodontitis, however, they can play a role in it, contributing to their severity and reactivation, consequently the planning of a therapy against these viruses can aid in periodontal treatment.

We acknowledge the financial support from University of Minho, Fundacao para a Ciencia e a Tecnologia (FCT) and FEDER-COMPETE through Centro de Quimica (UID/QUI/00686/ 2013 and UID/QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (RNRMN) and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/ 2005 with funds from POCI 2010 (FEDER) and FCT. This work was also developed under the scope of the project NORTE-01- 0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through FCT, under the scope of the project POCI-01- 0145-FEDER-007038. We also acknowledge the financial support by FCT through the postdoctoral grant awarded to Marta Costa (SFRH/BPD/79609/2011) and the PhD grant of Olivia Pontes (SFRH/BD/128850/2017).

The size of a farm is one of the factors that influence its productivity, in an ambiguous relationship that is often discussed in the industrial economy. In Portugal, the Demarcated Douro Region (DDR) is characterized by very small farms. Usually, this trend is considered a limitating factor in the profitability of the wine farms. In order to assess the correctness of this sentence, the variation of wine productivity per land size, from 2010 to 2016, was studied in the DDR, considering its three distinctive areas: Baixo Corgo, Cima Corgo and Douro Superior. The farms were categorized in nine different size ranges; as these variables outnumber the available seven observations, the Generalized Maximum Entropy (GME) estimator was used, since it suits the need to solve an ill-conditioned problem. GME was applied with the MATLAB (MATrix LABoratory) software along with the Bootstrap technique. According to the simulations, larger farms (with an area greater than 20 ha) on Douro Superior and Cima Corgo reveal higher marginal productivity given the current state of the region. On the other hand, Baixo Corgo's results suggest that medium-sized farms (with area ranges between 2 and 5 ha) display higher marginal increments to the region wine productivity. Keywords: Maximum-entropy, Wine productivity, Farm size

Cocoa farming in São Tomé and Príncipe (STP) faces several challenges due to its poor socioeconomic context, the adverse impact of climate changes, the complex and limited access to global value chains, and worldwide demand pressure for higher cocoa quality and productivity. This exploratory research investigates potential pathways to a more sustainable organic cocoa (OC) production in STP by mapping the perceptions of the stakeholders involved in its value chain. Qualitative interviews, field observation, and focus group discussions were applied to understand how sustainability dimensions, drivers, impacts, and challenges of OC are perceived and how these three dimensions can be improved and balanced. The gathered perceptions are rather diverse, reflecting the stakeholders’ position and knowledge of the specific contexts and processes. Producers do not perceive how governance is adopting new organizational structures or practices that allow for an effective sustainability improvement. Most stakeholders recognize that market-related factors drive the sustainability adoption and that financing-related constraints challenge their wide implementation. There are trade-offs and power asymmetries in the OC value chain, which manifest differently, due to the governance approaches, processes, overall regulations, and training of producers. An alignment of perceptions and activities as well as a stronger cooperation between cooperatives, private firms, and public institutions is strongly recommended.

Parallels between invertebrates and vertebrates in nervous system development, organisation and circuits are powerful reasons to use insects to study the mechanistic basis of behaviour. The last few years have seen the generation in Drosophila melanogaster of very large light microscopy data sets, genetic driver lines and tools to report or manipulate neural activity. These resources in conjunction with computational tools are enabling large scale characterisation of neuronal types and their functional properties. These are complemented by 3D electron microscopy, providing synaptic resolution data. A whole brain connectome of the fly larva is approaching completion based on manual reconstruction of electron-microscopy data. An adult whole brain dataset is already publicly available and focussed reconstruction is under way, but its 40× greater volume would require ∼500-5000 person-years of manual labour. Nevertheless rapid technical improvements in imaging and especially automated segmentation will likely deliver a complete adult connectome in the next 5 years. To enhance our understanding of the circuit basis of behaviour, light and electron microscopy outputs must be integrated with functional and physiological information into comprehensive databases. We review presently available data, tools and opportunities in Drosophila. We then consider the limits and potential of future progress and how this may impact neuroscience in rich model systems provided by larger insects and vertebrates.

Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder that affects movement coordination leading to a premature death. Despite several efforts, no disease-modifying treatment is yet available for this disease. Previous studies pinpointed the modulation of serotonergic signaling, through pharmacological inhibition of the serotonin transporter SERT, as a promising therapeutic approach for MJD/SCA3. Here, we describe the 5-HT1A receptor as a novel therapeutic target in MJD, using a C. elegans model of ATXN3 proteotoxicity. Chronic and acute administration of befiradol (also known as NLX-112), a highly specific 5-HT1A agonist, rescued motor function and suppressed mutant ATXN3 aggregation. This action required the 5-HT1A receptor orthologue in the nematode, SER-4. Tandospirone, a clinically tested 5-HT1A receptor partial agonist, showed a limited impact on animals' motor dysfunction on acute administration and a broader receptor activation profile upon chronic treatment, its effect depending on 5-HT1A but also on the 5-HT6/SER-5 and 5-HT7/SER-7 receptors. Our results support high potency and specificity of befiradol for activation of 5-HT1A/SER-4 receptors and highlight the contribution of the auto- and hetero-receptor function to the therapeutic outcome in this MJD model. Our study deepens the understanding of serotonergic signaling modulation in the suppression of ATXN3 proteotoxicity and suggests that a potent and selective 5-HT1A receptor agonist such as befiradol could constitute a promising therapeutic agent for MJD.

Summary A neuron responding to moist air and its ionotropic receptor have been identified in Drosophila melanogaster . Moreover, second-order neurons integrate temperature and humidity information before reaching higher brain centres.

1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain not entirely clear. We present a patient with a 2.3-Mb 1q44 deletion, including AKT3, ZBTB18, and HNRNPU, who shows microcephaly, developmental delay, abnormal corpus callosum, and seizures. The genetic findings in this case and a review of the literature spotlight a region between 243 Mb and 245 Mb on chromosome 1q related to the genesis of the typical symptoms of 1q44 deletion.

During the past sixty years, a lot of effort has been made regarding the productive efficiency. Such endeavours provided an extensive bibliography on this subject, culminating in two main methods, named the Stochastic Frontier Analysis (parametric) and Data Envelopment Analysis (non-parametric). The literature states this methodology also as the benchmark approach, since the techniques compare the sample upon a chosen “more-efficient” reference. This article intends to disrupt such premise, suggesting a mathematical model that relies on the optimal input combination, provided by a differential equation system instead of an observable sample. A numerical example is given, illustrating the application of our model’s features.

Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.

Microalgae when subjected to nutrient restriction conditions, inducing environmental stress, are prone to total lipid accumulation and changes in the fatty profile. In this context, the green microalgae Chlamydomonas sp. was submitted for 3 days to the absence of nutrients. Thus, the efficacy of the extraction of the crude hexane lipid fraction (CHF), using mechanical stirred associated with ultrasound technique, was evaluated in two different times (2 and 4 h), using scanning electron microscopy and thermogravimetric analysis (TG). Saponifiable fractions, CHF extracts and crude chloroform fraction (CCF) were esterified and characterized by TG, FTIR and GC/MS to identify their fatty profile. Residual biomass (RB) was analyzed by elemental analysis, and the resulting data were employed to estimate the higher heating value (HHV) and crude protein percentage. The micrographs of the biomass surfaces before and after the extraction process showed significant fragmentation only for the time of 4 h. A pronounced mass loss in the typical lipid range was evidenced by TG being consistent with the significant difference of material extracted in the time of 2 h (2.95 ± 0.28)% and 4 h (10.54 ± 0.46)%. The total lipid fraction (CHF and CCF) was approximately 29%. The RB revealed values of HHV and crude protein of 18 MJ kg−1 and 56%, respectively. The TG data for the CCF extract revealed a material consisting mainly of saponifiable fractions, unlike CHF which is composed predominantly of unsaponifiables. Therefore, the TG curve ratified a better conversion rate to CCF (approximately 89%), consistent with the value obtained by GC/MS (about 86%). The fatty profile for the saponifiable fractions of both extracts showed that the major fatty acids are C16:0 and C18:3 (ω-3 and ω-6). The ester profile with elevated concentration of polyunsaturated fatty acids (C18:3) is unfeasible in their application for biodiesel production; nevertheless, the fatty profile of microalgae suggests pharmacological potential for diet or therapy, since some of the main components are reported as bioactive metabolites.

1.Executive SummaryThis survey and data analysis were conducted by the European Network of Postdoctoral Associations (ENPA) with the aim of assessing the current research and work conditions, aspirations and support received by postdoctoral researchers working in Europe.The Results section is structured into three main parts. The first one describes the study sample of European postdoctoral researchers, including participants’ demographics, funding sources and income, research outputs, and teaching opportunities. The second section focuses on their professional aspirations and institutional support provided. The third part describes the level of engagement of postdoctoral researchers and their institutions in working towards better research conditions and career development, and what initiatives are emerging within this community.Our Conclusions section pulls together this comprehensive analysis, highlighting some of the most concerning issues currently affecting postdoctoral researchers in Europe. We also make a number of recommendations that would significantly improve the career expectations and aspirations of postdoctoral researchers. These are listed below.Conclusions and recommendationsLonger postdoctoral periods in Southern Europe despite higher publication metricsRecommendation Institutions in Southern Europe should develop clear criteria to support postdoctoral researchers’ career progression.Southern and Eastern Europe pay the lowest salaries and have the lowest number of foreign postdoctoral researchersRecommendation The salary differences across European countries should be addressed as this could be a barrier to mobility and knowledge exchange from higher to lower pay regions.Lack of access to funding is a significant concern of postdoctoral researchersRecommendation Discrepancies in access to funding should be minimized across the different European areas.Postdoctoral researchers in Europe work longer hours than required by contractRecommendation The culture of overwork in the research environment should be addressed in order to protect researchers against the risks associated with long hours at work.The majority of full-time postdoctoral work contracts includes an exclusivity clauseRecommendation Inclusion of exclusivity clauses in contracts for postdoctoral researchers should be optional in order to allow them to enhance their employability outside academia.Postdoctoral researchers’ career development is poorly supported by their institutionsRecommendation Postdoctoral researchers’ career prospects and career management should be much more supported by institutions in coordination with postdoctoral associations.Lack of postdoctoral representation in governance is linked to unclear institutional duties and rightsRecommendation Institutional governance bodies should include postdoctoral researcher representatives. This would ensure that the views of this vital staff group are heard, as well as making postdoctoral researchers feel more engaged with their own institutions. A flexible and proactive communication strategy at the institution and research group level should be developed, taking into account the sometimes transient nature of postdoctoral researchers’ posts.Researchers show higher engagement with their local postdoctoral associations than with workers’ unionsRecommendation Postdoctoral associations are an essential way to advocate for postdoctoral researchers at the governance level. Institutions should engage with, promote and support the work of postdoctoral associations.

The wine sector currently lacks nuclear fea-tures, which makes Portugal’s producing per-formance drift away from the frontline world-wide wine producers. The aim of this paper is to evaluate the evolution of the Portuguese wine industry’s performance through the world and national available statistical data. Also, this work tries to evaluate the sustainability dyna-mic regarding theNorth and Alentejo, using the Portuguese Farm Accountancy Data Network from 2001 to 2012. From the sustain-nability indicators, the results show that Alente-jo presents the best performance in terms of environmental sustainability. The North has an increasing economic dimension of sustainabil-ity and good social performance. The conclu-sions suggest that academic research can im-prove the wine industry’s overall orientation to sustainability. O setor vitivinícola carece atualmente de ca-racterísticas nucleares que fazem o desempenho produtivo do país afastar-se dos líderes da pro-dução mundial de vinho. O objetivo deste traba-lho consiste em avaliar a evolução do desempe-nho do setor vitivinícola português através dos dados estatísticos disponíveis, a nível mundial e nacional. Pretende-se ainda avaliar a dinâmica da sua sustentabilidade, no Norte e Alentejo, através dos dados da Rede de Informação de Contabilidade Agrícola de 2001 a 2012. Dos indicadores de sustentabilidade obtidos verifi-ca-se que o Alentejo obtém o melhor desempe-nho em termos de sustentabilidade ambiental. O Norte tem uma tendência para melhorar a di-mensão económica da sustentabilidade e revela bom desempenho social. As conclusões suge-rem que a investigação académica pode melho-rar a orientação geral desta indústria para a sua sustentabilidade. info:eu-repo/semantics/publishedVersion

Nos dias de hoje é, cada vez mais comum, em unidades fabris, a utilização de robôs de distribuição, em ambientes logísticos, de determinadas peças essenciais para a fabricação de outras, constituindo assim, todo o processo de produção da empresa. O contributo humano, na realização destas tarefas é cada vez menos vantajoso, na medida em que as tarefas que não podem ser realizadas por máquinas começaram a ficar atrasadas ou adiadas para o dia seguinte, provocadas por uma excessiva carga de trabalho sentida pelos conferentes do armazém PHF. Juntando a este facto, o da necessidade de determinados artigos ou materiais ser urgente e de os colaboradores da Renault Cacia poderem adquiri-los sem terem de se deslocar ao armazém e, simultaneamente, sem que os responsáveis do mesmo tenham de os ir distribuir aos diferentes setores e ateliers, contribuiu para que surgisse, desta forma, um projeto de distribuição automática de artigos, para substituir a manual, auxiliada por um carro Bull. Assim, ao longo deste documento, é estudada a hipótese de desenvolvimento de um meio de distribuição automática do armazém PHF, localizado fora das naves fabris, para toda a fábrica, culminando com a decisão de alugar um AGV, Automated Guided Vehicle, para concretização da mesma. Através da aplicação de diversas ações e resolução de várias tarefas que vão de encontro à concretização dos objetivos esperados, foram encontrados entraves e contratempos, diariamente, que puseram em causa o funcionamento do novo método adotado, mas que, no final, deram sentido ao novo procedimento e o enriqueceram, proporcionando oportunidade para que este vingasse e alcançasse os resultados pretendidos, tendo margem de manobra para possíveis melhorias. A distribuição, passou a ser realizada de uma forma mais automática, apesar de ainda não ser a 100%, o rendimento de trabalho dos colaboradores da Renault Cacia aumentou, assim como os ganhos consequentes, verificados na produção da mesma. A taxa de serviço ao cliente aumentou, assim como o funcionamento do armazém PHF, ganhou outra desenvoltura e, neste momento, os seus conferentes estão mais libertos para poderem desempenhar as suas funções Nowadays, it is increasingly common in production units to use robots for the distribution of certain pieces, that are essential for the manufacture of others, in a logistic environment, and thus constitute the entire production process of the company. The human contribution in the case of on-going is less advantageous, once that the tasks, which can’t be carried out by a machine, started to be deferred to the next day, caused by excessive workload felt by the warehouse PHF. Furthermore, the urgent need of certain articles or materials felt by the workers, the fact that they can have them without having to go to the warehouse to pick them, and the responsibles of the PHF don’t have to make the distribution of the same articles through the sectors and ateliers, contributed to the creation of the project of the automatic distribution of the articles, to substitute the manual one, that has been done with the Bull car. Thus, throughout this document, a simulation of the development of a PHF distribution made from the outside of the ship factories to the inside, is studied for an entire factory, with the participation of an AGV, Automated Guided Vehicle, for the realization of the job and performance. Through the application of various actions and resolution of various tasks that meet the expected objectives, obstacles and setbacks were found, on a daily basis, that reorganized the functioning of the new method adopted, but which, in the end, gave meaning to the new procedure and enriched it by giving it an opportunity to achieve the desired results, with room for possible improvements and achievements. The distribution started to be executed in a more automatic way. Although not at 100%, the work income of the employees of the Renault Cacia increased, as well as the consequent gains obtained in the production cicle. The customer service increased, as well as the operation of the PHF warehouse, has gained a new edge and at this time, once that its workers are more freed up to be able to perform their duties. Mestrado em Engenharia e Gestão Industrial

No question remains regarding our need to change toward sustainable agriculture. When ranking the industries that have more prevalent environmental impacts, agriculture holds a considerable share of responsibility. However, as sustainability is an ambiguous concept surrounded by controversy and debate, rather than attempt to describe its meaning through a single universal definition, we instead stressed the need to delineate a set of fundamental principles. With the goal of putting the sustainable-agriculture concept into practice, an inductive qualitative content analysis was employed based on multivariate methods on hundreds of different definitions, theories, notions and sustainability indicators gathered through a deep-structured literature review. Through this novel approach, we were able to identify four fundamental principles for sustainable agriculture (integrated management, dynamic balance, regenerative design, and social development), and concluded that in order to shift our current agricultural systems into more efficient and sustainable ones, we need to start making better use of natural and human resources. This work provides guidelines for reference that can be used by anyone whenever they make a decision regarding sustainable agriculture or apply a methodology to assess a particular behavior, process or situation.

Summary Nervous systems contain sensory neurons, local neurons, projection neurons, and motor neurons. To understand how these building blocks form whole circuits, we must distil these broad classes into neuronal cell types and describe their network connectivity. Using an electron micrograph dataset for an entire Drosophila melanogaster brain, we reconstruct the first complete inventory of olfactory projections connecting the antennal lobe, the insect analog of the mammalian olfactory bulb, to higher-order brain regions in an adult animal brain. We then connect this inventory to extant data in the literature, providing synaptic-resolution “holotypes” both for heavily investigated and previously unknown cell types. Projection neurons are approximately twice as numerous as reported by light level studies; cell types are stereotyped, but not identical, in cell and synapse numbers between brain hemispheres. The lateral horn, the insect analog of the mammalian cortical amygdala, is the main target for this olfactory information and has been shown to guide innate behavior. Here, we find new connectivity motifs, including axo-axonic connectivity between projection neurons, feedback, and lateral inhibition of these axons by a large population of neurons, and the convergence of different inputs, including non-olfactory inputs and memory-related feedback onto third-order olfactory neurons. These features are less prominent in the mushroom body calyx, the insect analog of the mammalian piriform cortex and a center for associative memory. Our work provides a complete neuroanatomical platform for future studies of the adult Drosophila olfactory system., Graphical Abstract, Highlights • First complete parts list for second-order neurons of an adult olfactory system • Quantification of left-right stereotypy in cell and synapse number • Axo-axonic connections form hierarchical communities in the lateral horn • Local and memory-related feedback target projection neuron axons, Bates, Schlegel et al. report the first complete part list of second-order neurons in an adult arthropod olfactory system. They show that these neurons are stereotyped across hemispheres and reveal their hierarchical interconnectivity and how they connect to third-order targets and memory-related neurons.

Este artigo trata de um estudo do imaginário lúdico através do movimento corporal de crianças de uma escola pública, localizada na cidade de Niterói/RJ. Pretendeu-se construir uma pesquisa dos sentidos, com vistas a trazer à tona reflexões sobre a tensão entre a potência das manifestações corporais e os fazeres docentes revelados na dinâmica lúdico simbólica das crianças, em atividades de jogos e brincadeiras. O estudo se fundamentou na perspectiva teórico-metodológica da sociologia compreensiva de Michel Maffesoli e na teoria da complexidade de Edgar Morin. Os estudos do imaginário, os estudos sobre corpo, e a pesquisa narrativa, alinharam-se ao referencial teórico-metodológico, de modo a capturar os sentidos dos espaços revelando a cultura das crianças (modos de pensar, sentir e agir), pela expressividade de suas múltiplas linguagens, especialmente a linguagem corporal. Por meio da cartogênese, uma das heurísticas utilizadas para capturar manifestações simbólicas, foi revelado que a linguagem corporal das crianças do estudo remetem à heroicidade e ao afeto. Acreditamos que a pesquisa mostrou que a saída para a crise atual do paradigma dominante será o aparecimento de um novo paradigma, que não negue o anterior, mas que transforme o ‘olhar’ do homem para a realidade dada; que não exclua a emoção, a beleza, a ética e a estética e, sobretudo, o corpo que, por imagens simbólicas, expressa sentimentos, emoções e formas de ser e estar no mundo.

Prescription patterns of non-vitamin K antagonist oral anticoagulants (NOACs) are unknown among primary care physicians, where most patients with nonvalvular atrial fibrillation (NVAF) are diagnosed and followed up. The goal of this study was to evaluate overdosing and underdosing of NOACs in patients with NVAF followed up in primary care and determine their clinical predictors.This multicenter cross-sectional study included all patients with NVAF followed up in 13 primary care units in the center region of Portugal. Patients receiving antithrombotic regimens other than NOACs and patients with missing data were excluded.The study included 858 patients with NVAF on an NOAC regimen. Overall, 30.3% were prescribed an off-label dosage (25.4% with infratherapeutic dosing [ITD] and 4.9% with supratherapeutic dosing). Chronic kidney disease (odds ratio, 14.0; 95% CI, 5.4-36.5; P 0.001) and female sex (odds ratio, 2.6; 95% CI, 1.2-5.7; P 0.001) were independent predictors of supratherapeutic dosing. We also found a significant effect of chronic kidney disease on ITD (odds ratio, 0.22; 95% CI, 0.258-0.678; P 0.001).In primary care, NOACs are frequently prescribed with unadjusted dosages, generally infratherapeutic. Attention should be paid to women and patients with chronic kidney disease.

Animals exhibit innate behaviours in response to a variety of sensory stimuli such as olfactory cues. In Drosophila, a higher olfactory centre called the lateral horn (LH) is implicated in innate behaviour. However, our knowledge of the structure and function of the LH is scant, due to the lack of sparse neurogenetic tools for this brain region. Here we generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell-types. We identify the neurotransmitter and axo-dendritic polarity for each cell-type. Using these lines were create an anatomical map of the LH. We found that ∼30% of LH projections converge with outputs from the mushroom body, the site of olfactory learning and memory. Finally, using optogenetic activation of small groups of LH neurons. We identify cell-types that drive changes in either valence or specific motor programs, such as turning and locomotion. In summary we have generated a resource for manipulating and mapping LH neurons in both light and electron microscopy and generated insights into the anatomy and function of the LH.

Chalcone and chromene derivatives were synthesized in good yield through simple and effective reactions using innocuous solvents such as water and ethanol and high yielding aldol condensations. Generally, the reactions were performed at room temperature, leading to the isolation of highly pure compounds. These compounds were tested on breast cancer cells (MCF-7 and Hs578T) and breast non-neoplastic cells (MCF-10A). After determination of IC50 value, specific assays were performed to analyze the potential of these compounds, and those bearing halogenated substituents presented enhanced activity comparing to methoxyl or methyl groups. More specifically, the bromine atom was often present in the bioactive molecules that proceeded to the final assays and showed to be promising candidates for further studies. The selected chromene acted as a cell migration inhibitory agent and triggered regulated cell death associated with G2/M cell-arrest and microtubule destabilization. For chalcones, the results suggest an anti-proliferative activity. Also, results for combination-therapy potentiated the antitumor effect of doxorubicin and reduced cytotoxicity in MCF-10A cells., We acknowledge the financial support from University of Minho, Fundaçao para a Ci ~ encia e a Tecnologia and FEDER- ^ COMPETE for financial support through Centro de Química (UID/ QUI/00686/2013 and UID/QUI/0686/2016), and for the postdoctoral grants awarded to Marta Costa (SFRH/BPD/79609/2011) and Belem Sampaio-Marques (SFRH/BPD/90533/2012), PhD grants of Filipa Santos (SFRH/BD/87139/2012) and Olívia Pontes (SFRH/BD/128850/ 2017). The confocal microscope Olympus FV1000 acquired under the financial support of PPBI-POCI-01-0145-FEDER-022122. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (RNRMN) and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. This work was also developed under the project NORTE-01-0145- FEDER-000013, by the Northern Portugal Regional Operational Program (NORTE 2020), through the European Regional Development Fund (FEDER) and the Competitiveness Factors Operational Program (COMPETE) and by National funds, through the Foundation for Science and Technology (ref. POCI-01-0145-FEDER007038).

Evolution has shaped nervous systems to produce stereotyped behavioural responses to ethologically relevant stimuli. For example when laying eggs, female Drosophila avoid geosmin, an odorant produced by toxic moulds. Here we identify second, third, and fourth order neurons required for this innate olfactory aversion. Connectomics data place these neurons in a complete synaptic circuit from sensory input to descending output. We find multiple levels of valence-specific convergence, including a novel form of axo-axonic input onto second order neurons conveying another danger signal, the pheromone of parasitoid wasps. However, we also observe extensive divergence: second order geosmin neurons connect with a diverse array of 80 third order cell types. We find a pattern of convergence of aversive odour channels at this level. Crossing one more synaptic layer, we identified descending neurons critical for egg-laying aversion. Our data suggest a transition from a labelled line organisation in the periphery to a highly distributed central brain representation that is then coupled to distinct descending pathways.

Gastric volvulus is an uncommon cause of gastric obstruction. It can be classified as primary when no underlying condition is identified as the cause for the rotation. An acute presentation includes typical symptoms and is frequently detected by imaging studies. Chronic cases present with intermittent vague symptoms and imaging studies may be normal during the symptomatic interval. The lack of specific symptoms and signs delays the diagnosis of chronic volvulus. However, appropriate treatment demands prompt diagnosis. We report two cases of primary gastric volvulus, with chronic or subacute symptoms and normal imaging studies during the asymptomatic periods. Both were treated surgically and had an uneventful follow-up.

Skin to skin contact (SSC) between mother and child immediately after birth is now considered to be an indicator of good clinical practice as it offers multiple benefits for both: it reduces stress levels of the mother, it facilitates affective bonding, breastfeeding and the newborns adaptation to extra-uterine life. However, in the vast majority of hospitals, mother and child are separated until complete recovery following a caesarean section, which can be several hours. In this article the advantages of SSC after a caesarean section, were analyzed, as well as the main difficulties in order to carry it out, which include maternal or neonatal instability and the reticence of the professionals themselves. An actuation procedure model is detailed, for its implementation in a safe manner and that at the same time, contribute to humanize the birth.El contacto piel con piel (CPP) entre la madre y el recién nacido tras el nacimiento es considerado como uno de los indicadores de Buenas Prácticas Clínicas, ya que ofrece múltiples beneficios para ambos: reduce el nivel de estrés en la madre, facilita el desarrollo del vínculo afectivo, el éxito de la lactancia materna y la adaptación del recién nacido a la vida extrauterina. Sin embargo, en la mayoría de los hospitales se separa a madre e hijo el tiempo que dura la recuperación tras la cesárea, lo que puede extenderse varias horas. En este artículo se analizaron las ventajas del CPP tras las cesáreas y las principales dificultades para llevarlo a cabo, que incluyen inestabilidad materna o neonatal y reticencias de los propios profesionales. Se detalla un modelo de procedimiento de actuación para su puesta en marcha, de forma segura y que a la vez contribuya a humanizar el nacimiento.

In pursuit of palatable food, hungry animals mobilize significant energy resources and overcome obstacles, exhaustion and fear. Their perseverance depends on metabolic state, internal motivation and the expected benefit. Sustained commitment to a trying task is crucial, however, disengagement from one behavior to engage into another can be essential for optimal adaptation and survival. How neural circuits allow prioritizing perseverance over withdrawal based on the animal's need, however, is not understood. Using a single fly spherical treadmill, we show that hungry flies display increasing perseverance to track a food odor in the repeated absence of the predicted food reward. While this perseverance is mediated by a group of dopaminergic neurons, a subset of neurons expressing octopamine, the invertebrate noradrenaline, provide reward feedback and counteract dopamine-motivated food seeking. Our data and modeling suggest that two important neuromodulators tally internal and external signals to ultimately coordinate motivation-dependent antagonistic behavioral drives: perseverance vs. change of behavior.

Accurately predicting an outcome requires that animals learn supporting and conflicting evidence from sequential experience. In mammals and invertebrates, learned fear responses can be suppressed by experiencing predictive cues without punishment, a process called memory extinction. Here, we show that extinction of aversive memories in Drosophila requires specific dopaminergic neurons, which indicate that omission of punishment is remembered as a positive experience. Functional imaging revealed co-existence of intracellular calcium traces in different places in the mushroom body output neuron network for both the original aversive memory and a new appetitive extinction memory. Light and ultrastructural anatomy are consistent with parallel competing memories being combined within mushroom body output neurons that direct avoidance. Indeed, extinction-evoked plasticity in a pair of these neurons neutralizes the potentiated odor response imposed in the network by aversive learning. Therefore, flies track the accuracy of learned expectations by accumulating and integrating memories of conflicting events.

Understanding the role of the climate on the wine production is one of the major concerns of this sector since the environment usually determines the output of this industry. There are only a few previous studies that attempted to compile these environmental effects as an index, usually considering the temperature and the precipitation as their core variables. The present study suggests a new climate index which is based on descriptive statistics. Our index tries to mimic the target region characteristics and avoid the past studies premise of imposing previously conceived restrictions such as a fixed optimal climate. We then used yearly production and daily temperature data (1950-2016) from the Portuguese Minho wine region to test our proposed index and compare it with Ribéreau-Gayon and Peynaud (RGP, Ribéreau-Gayon et al., 2003) and Growing Degree-Days (GDD, Winkler et al., 1974) indexes. Our results showed that the newly proposed index may outperform the explanatory power of the other indexes and, in addition, may output interesting and unknown characteristics such as the different ideal temperatures regarding the studied region.

To determine the key variables of the vineyard efficiency is imperative to account the combined effects of the inputs interactions since they have implications on the overall final production. This paper estimates the productive efficiency of a wine-farm sample from the Douro Demarcated Region (DDR) while identifies economic, social and environmental indicators that characterizes the DDR grape production system. The data was collected by face-to-face surveys performed at farm level to build a pilot study. The majority of the sampled twenty farms are dedicated to mountain viticulture and mainly feature the cordon (simple and double) training system. Through the Data Envelopment Analysis (DEA) method, the productive efficiency of the sampled was performed and the results clinched different efficiency scores. The main explanation is related to the heterogeneity of the adopted production system. In addition, they revealed how grape producers could improve their productive efficiency by adopting particular practices and identifying the key factors of their system.