Repositório RCAAP

In October 2017, hundreds of wildfires ravaged the forests of the north and centre of Portugal. The fires were fanned by strong winds as tropical storm Ophelia swept the Iberian coast, dragging up smoke (together with Saharan dust from north-western Africa) into higher western European latitudes. Here we analyse the long-range transport of particulate matter (PM10) and study associations between PM10 and short-term mortality in the Portuguese population exposed to PM10 due to the October 2017 wildfires, the worst fire sequence in the country over the last decades. We analysed space- and ground-level observations to track the smoke plume and dust trajectory over Portugal and Europe, and to access PM10 concentrations during the wildfires. The effects of PM10 on mortality were evaluated using satellite data for exposure and Poisson regression models. The smoke plume covered most western European countries (including Spain, France, Belgium and the Netherlands), and reached the United Kingdom, where the population was exposed in average to an additional PM10 level of 11.7 µg/m3 during seven smoky days (three with dust) in relation to the reference days (days without smoke or dust), revealing the impact of the wildfires on distant populations. In Portugal, the population was exposed in average to additional PM10 levels that varied from 16.2 to 120.6 µg/m3 in smoky days with dust and from 6.1 to 20.9 µg/m3 in dust-free smoky days. Results suggest that PM10 had a significant effect on the same day natural and cardiorespiratory mortalities during the month of October 2017. For every additional 10 µg/m3 of PM10, there was a 0.89% (95% confidence interval, CI, 0-1.77%) increase in the number of natural deaths and a 2.34% (95% CI, 0.99-3.66%) increase in the number of cardiorespiratory-related deaths. With rising temperatures and a higher frequency of storms due to climate change, PM from Iberian wildfires together with NW African dust will tend to be more often transported into Northern European countries, which may carry health threats to areas far from the ignition sites.

Aim Few bird extinctions on oceanic island have been attributed to competition with non-native species, even though it might be an overlooked driver of biodiversity loss. We evaluate the potential competition between native and non-native island bird species, identifying species and island characteristics that enhance it and may promote future extinctions. Location Seventy-three (>100 km2) oceanic islands worldwide. Methods We compiled a species list for each island and used single-trait meta-analyses to assess differences between native and non-native species. Then, we used single-trait beta regression models to identify species traits linked to potential competition. Finally, we used a trait-based approach to calculate the potential competition between native and non-native species on each island and identify island characteristics linked to potential competition. Results Native bird species tended to be smaller forest dwellers, that were either carnivore, frugivore or insectivore, and that foraged in flight, in the canopy or at mid-height. In contrast, non-native birds tended to be open habitat granivores, that were either ground or unspecialized foragers. Potential competition tended to be higher for native species with typical non-native traits and forest-dwelling unspecialized non-native species. Potential competition between native and non-native birds was consistently higher in islands that were larger, had more non-native birds or were drier. Main conclusions Niche differentiation of native and non-native species may explain the scarcity of reported competition-driven extinctions since non-natives clearly tend to favour and are better adapted to anthropogenic environments. However, the few non-native birds that occur in native ecosystems may be problematic. The loss of native ecosystems coupled with the introduction of species that might outcompete native species may enhance the relevance of competition in future island extinctions.

The Instituto de Investigação Científica Tropical, University of Lisbon (IICT), Portugal, holds the most important scientific collections from Portuguese-speaking African countries, which include anthropological, archaeological, ethnographic, mineralogical, botanical and zoological collections, as well as libraries and historical archives. The aim of this paper is to document the advances in conservation and management of IICT collections between 2005 and 2015, namely how the implementation of institutional initiatives created new challenges for the scientific community. After an overview of the IICT's scientific heritage since the creation of the Cartography Commission in 1883, we characterise several recent actions aimed at preserving and providing access to the collections. Considerations on the current preservation of the IICT collections are presented. It is argued that these collections are unique for tropical science and of critical importance for scientific cooperation with Portuguese-speaking countries in Africa.

Este número temático é fruto também de muito trabalho de cuidado activista e académico, que (tal como o cuidado doméstico) é invisível, desvalorizado e não reconhecido (Federici, 2019; Barca, 2020a, 2020b).2 Um processo contínuo de motivar, sensibilizar, articular pessoas, conhecimentos, visões de mundo, expectativas e de responder às solicitações adaptando-as ao “possível” e à construção de algo que nos faça sentido colectivamente. Editar este número temático juntando academia e activismo – e em especial numa altura de grandes perturbações e mudanças de rotina da organização da vida causadas pela pandemia – foi uma intensa caminhada recheada de aprendizagem e desafio. Estamos muito gratas a todas as pessoas que, de alguma forma, contribuíram para este resultado colectivo. Contámos com o trabalho incansável de toda a equipa editorial, mas deixamos um especial agradecimento à Ana Sofia Veloso e à Alina Timóteo. Agradecemos também a colaboração de todas/os3 que contribuíram com textos, e que participaram no processo de revisão por pares. É importante reconhecer também o trabalho das investigadoras Begoña Dorronsoro e Paula Sequeiros, que participaram na organização dos Encontros e deram força ao projecto de organização deste número. A revisão da Introdução contou com contributos valiosos de Stefania Barca e Sérgio Pedro, a quem estamos também muito gratas. De entre as pessoas envolvidas muitas são mulheres, que passaram a ter uma ainda maior sobrecarga de trabalho decorrente da actual situação pandémica, dos confinamentos, do acompanhamento de filhas/os e outros familiares, e da necessidade de permanência em casa por precaução ou doença. Tiveram uma maior dificuldade em conciliar o trabalho remunerado (presencial ou remoto) com o trabalho não remunerado e viram-se confrontadas com novas necessidades de cuidados, nomeadamente a nível da saúde mental.

Small RNA molecules play major roles in a number of cellular functions. Depending on their predominant cellular location, small RNAs have been classified as nuclear (sn), nucleolar (sno) or cytoplasmic (sc). The nucleoplasmic species include the spliceosomal snRNAs (U1, U2, U4, U5 and U6) and the U7 snRNA required for histone pre-mRNA 3′-end formation.

Background and aims: Concurrent therapies are not accounted for nutritional intake. This prospective clinical audit in an intensive care unit aimed at assessing the influence of fluid therapy and drugs containing nutrients on total nutrient delivery. Methods: Forty-four patients, 25M: 19F, age 63+/-12 (17-83)years, Acute Physiological and Chronic Health Evaluation II: 24+/-9, with length of stay >72h, were evaluated. Basal energy expenditure was estimated by the Harris-Benedict formula. All nutrients conveyed by oral, enteral, parenteral nutrition, IV solutions and drugs were daily registered and summed at the end of respiratory intensive care unit stay. Results: Mean estimated basal energy expenditure (BEE), 1372+/-432 kcal/day, was lower than mean caloric intake 2034+/-432 kcal/day (P<0.05), >BEE in 54% of patients. When dextrose/propofol were excluded, mean energy intake, 1375+/-430 kcal/day, was similar to BEE; 93% and 86% of patients had an adequate carbohydrate and lipid intake, respectively. Dextrose determined an excessive carbohydrate delivery, higher than 58% of calories, in 43% of patients, while 84% had an excessive lipid delivery due to propofol. Excessive sodium from normal saline was administered to 91% of patients, though 43% had overt oedema. Conclusions: Hypernutrition ensued from non-quantified fluid therapy/drugs. Sodium loads may aggravate lung and gut dysfunction. The provision of "occult" calories and minerals may be quite substantial and should be taken into consideration.

A nationwide multicenter study (including 31 laboratories) of the antimicrobial susceptibility of 1210 Streptococcus pneumoniae isolates from patients with community-acquired lower respiratory tract infections (LRTI) was carried out over 3 years (1999-2001) in Portugal. Testing of all isolates was undertaken in a central laboratory. Overall macrolide resistance was 13.1%. Decreased susceptibility to penicillin was 24.5% (15.5% low-level and 9.0% high-level resistance). Taken into consideration, the resistance rates reported in a previous surveillance study of 1989-1993, a six-fold increase of erythromycin resistance in the last decade was documented. Resistance to erythromycin, clarithromycin, and azithromycin was higher in pediatric patients than in adults. The overwhelming majority (82.3%) of macrolide-resistant isolates were multidrug resistant, although 44.9% were fully susceptible to penicillin. Most macrolide-resistant isolates (80.4%) showed the MLSB phenotype (76.6% MLSB-constitutive resistance, and 3.8% MLSB-inducible resistance) and were also resistant to clindamycin, tetracycline, and co-trimoxazole. The M phenotype was seen in 19.6% isolates and these had MIC90 values of 8 mg/L for erythromycin and clarithromycin, and of 12 mg/L for azithromycin. The clinical significance of macrolide resistance in the management of LRTI is discussed. Because of the specific situation concerning macrolide resistance described in S. pneumoniae, careful use of macrolide antibiotics in therapy and cautious monitoring of macrolide resistance should be continued in Portugal.

No summary/description provided

Nesta tese, colocamo-nos no contexto do sistema do Great Plains Low-Level Jet (GPLLJ), que é um sistema de ventos muito fortes na troposfera inferior que transporta uma enorme quantidade de humidade do Golfo do México para as Grandes Planícies Americanas e está principalmente activo nos meses de Verão. Este trabalho tem dois objectivos: primeiro, analisar o comportamento extremo da humidade transportada da região de origem do GPLLJ para o domínio do jet; segundo, nos casos de humidade transportada baixa e alta, estudar a dependência global e extrema entre a cauda superior da precipitação na região do sumidouro do GPLLJ e a cauda inferior da estabilidade troposférica na região do sumidouro do GPLLJ (ómega). Para este efeito, são utilizadas as séries de observações diárias de humidade transportada, precipitação e "ómega" de todos os períodos de Junho-Julho-Agosto de 1980 a 2017, o que corresponde a 3496 observações. As observações de precipitação e "ómega" foram separadas em dois grupos consoante os valores observados de humidade transportada. Um valor de humidade transportada é considerado baixo, se for inferior ao correspondente quantil empírico de probabilidade 0.25 e alto, se exceder o quantil de probabilidade 0.75 dessa variável. No que diz respeito à parte teórica desta dissertação, em primeiro lugar são apresentados os conceitos fundamentais da Teoria Univariada de Valores Extremos. É relevante salientar a importância dos modelos de limiar, que são essenciais para ambos os objectivos da tese: realizar a análise univariada dos extremos de humidade transportada e como passo prévio necessário ao estudo dos extremos bivariados. A seguir, é possível encontrar alguns dos tópicos-chave da Teoria Bivariada de Valores Extremos, que foi utilizada para abordar a abordagem de extremos que constitui o segundo objectivo desta tese. São apresentadas as noções probabilísticas fundamentais e alguns dos modelos paramétricos mais importantes dos extremos bivariados, para além da metodologia estatística mais comum neste contexto. Particularmente importante é o método de verosimilhança censurada, que é utilizado para ajustar o Modelo de Limiar Bivariado de Excessos na modelação dos dados. Também é abordado o conceito de independência assintótica, que é uma situação que deve ser analisada quando se utiliza a metodologia apresentada nesta tese. A fim de obter uma imagem global da estrutura de dependência no contexto do segundo objectivo deste trabalho são utilizadas cópulas. É apresentado um resumo dos aspectos mais importantes da Teoria de Cópulas, tanto do ponto de vista probabilístico como do ponto de vista estatístico. Nomeadamente, introduzimos o conceito de copula, alguns dos modelos de cópulas mais comuns e apresentamos diferentes métodos de estimação (embora o foco seja a abordagem semi-paramétrica, que é usada na parte prática da tese), bem como algumas breves considerações sobre a selecção de modelos e testes de ajustamento das cópulas. Posteriormente, são apresentados o procedimento e os resultados relativamente à análise univariada de extremos de humidade transportada. Depois de realizar uma breve análise exploratória a fim de compreender melhor a série em estudo, são utilizados modelos de limiar para estudar o comportamento dos valores extremos dessa série. Utiliza-se a abordagem conhecida como Peaks Over Threshold (POT), traduzido para português como “Picos acima do limiar”. Através de dois dos métodos mais habituais de selecção de limiares, é decidido que u = 2 (mm/dia) é um limiar adequado. Como é claramente visível que os excessos em relação ao limiar escolhido não são independentes, é feito um processo de declustering (usando o método de "run-declustering") a fim de eliminar o mais possível essa dependência. O declustering foi realizado considerando quatro valores diferentes de run length (r), nomeadamente 1,2,3 e 4. Graficamente e por testes estatísticos, chegamos à conclusão de que o modelo exponencial é mais apropriado do que o modelo de Pareto Generalizado (GPD, pelo seu acrónimo em inglês) para modelar os máximos de clusters de excessos acima do limiar escolhido, para todos os valores de r considerados. Além disso, prova-se que no caso de r = 4 o modelo exponencial não estacionário é mais adequado do que o estacionário, no sentido em que se demonstra que o parâmetro de escala do modelo exponencial decresce com o tempo. Por esta razão e porque é o valor que garante melhor a independência entre os excessos, conclui-se que r = 4 é a melhor escolha. Também são calculados os níveis de retorno estimados de 38 anos, 50 anos e 100 anos para a série de humidade transportada utilizando o modelo exponencial não estacionário ajustado aos máximos dos clusters de excessos. É interessante referir que nesta abordagem o período "um ano" corresponde a "um verão" (meses de Junho, Julho e Agosto). Os resultados desses cálculos mostram que os três níveis de retorno estimados foram diminuindo com o tempo e que a diferença entre eles se tornou menor. Por conseguinte, é possível dizer que esperamos observar valores extremos mais baixos de humidade transportada no futuro. Por outro lado, são analisados os extremos bivariados de (-ómega,precipitação) nos casos de humidade transportada baixa e alta. Note-se que o sinal de "ómega" é trocado porque, em termos meteorológicos, o interesse é estudar o comportamento conjunto da cauda superior de precipitação e da cauda inferior de "ómega". As séries de precipitação e "-ómega" são desfasadas 1 dia em relação à série de humidade transportada devido à natureza temporal do sistema do GPLLJ. Após uma análise preliminar dos dados em estudo, inicia-se o processo de ajustamento do Modelo de Limiar Bivariado de Excessos. Para tal, é necessário previamente ajustar modelos univariados de limiar às margens. Conclui-se que, tanto nos casos de humidade transportada baixa como alta, um limiar adequado para "-ómega" é u1 = 0.03 (Pa/s) e, para precipitação, é adequado escolher u2 = 5.2 (mm/dia). Usando esses limiares, o modelo GPD é mais apropriado do que o exponencial no caso de "-ómega", verificando-se o contrário no caso da precipitação, tanto nos casos de humidade transportada baixa como alta. Tendo escolhido essas distribuições para os excessos acima do respectivo limiar em cada margem, é utilizado o método de verosimilhança censurada considerando oito diferentes modelos paramétricos. É demonstrado que, para todos esses modelos, a dependência extrema entre "-ómega" e precipitação é mais forte no caso de humidade transportada alta do que quando ela é baixa. Os valores do critério de informação de Akaike (AIC, pelo seu acrónimo em inglês) correspondentes a cada um desses modelos são também calculados e o modelo mais parcimonioso no caso de humidade transportada baixa é o bilogístico, enquanto que no caso de ela ser alta, é o logístico. É apresentada a informação mais relevante sobre o modelo bilogístico ajustado no caso de humidade transportada baixa e o modelo logístico ajustado para o caso de ela ser alta. Apresentam-se as estimativas de máxima verosimilhança dos seus coeficientes, as suas correspondentes funções de dependência de Pickands, bem como algumas curvas de quantis estimadas que foram construídas utilizando estes modelos. Além disso, através dos gráficos destinados a esse fim, chega-se à conclusão de que podemos assumir que as variáveis são assimptoticamente dependentes, e portanto os modelos que são apresentados na parte teórica da tese são apropriados para este par de variáveis, tanto nos casos de humidade transportada baixa como alta. Por fim, são ajustadas cópulas ao par (-ómega,precipitação), tanto nos casos de humidade transportada baixa como alta. Chega-se à conclusão de que a dependência global entre "-ómega" e precipitação é mais forte no caso de humidade transportada alta do que quando ela é baixa. Além disso, através das estimativas dos coeficientes de dependência de cauda, vemos que a dependência superior de cauda entre "-ómega" e precipitação é mais forte no caso de humidade transportada alta do que quando ela é baixa, resultado que está em consonância com as conclusões obtidas a partir do estudo dos extremos bivariados. Além disso, utilizando cópulas, chega-se à mesma conclusão no que se refere à dependência inferior de cauda. De acordo com os testes de ajustamento realizados às cópulas t de Student e Gumbel em cada caso de humidade transportada baixa e alta, esses modelos mostraram ser apropriados em ambos os casos. De acordo com os valores de AIC, a cópula t de Student é o modelo mais adequado no caso de humidade transportada baixa e a cópula Gumbel quando ela é alta. Finalmente, usando estas duas cópulas ajustadas, traçaram-se as funções de densidade dos modelos ajustados. A comparação das pseudo-observações com dados simulados a partir das cópulas ajustadas permite-nos pensar que os modelos são adequados.

The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings. Here, we discuss how different classes of surface receptors impact on human and murine γδ T-cell differentiation, activation, and expansion. In particular, we review the role of five receptor types: the T-cell receptor (TCR), costimulatory receptors, cytokine receptors, NK receptors, and inhibitory receptors. Some of the key players are the costimulatory receptors CD27 and CD28, which differentially impact on pro-inflammatory subsets of γδ T-cells; the cytokine receptors IL-2R, IL-7R, and IL-15R, which drive functional differentiation and expansion of γδ T-cells; the NK receptor NKG2D and its contribution to γδ T-cell cytotoxicity; and the inhibitory receptors PD-1 and BTLA that control γδ T-cell homeostasis. We discuss these and other receptors in the context of a five-step model of receptor signaling in γδ T-cell differentiation and activation, and discuss its implications for the manipulation of γδ T-cells in immunotherapy.

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells. The data showed that positively charged peptide entities composed of arginines alone and with an isoelectric point at and above 12.6 are necessary and sufficient for mediating significant nucleolar accumulation. A threshold of 6 arginines is necessary for peptides to accumulate in nucleoli, but already 4 arginines are sufficient when fused within 15 amino acid residues of a nuclear localization signal of a protein. Using a pH sensitive dye, we found that the nucleolar compartment is particularly acidic when compared to the surrounding nucleoplasm and, hence, provides the ideal electrochemical environment to bind poly-arginine containing proteins. In fact, we found that oligo-arginine peptides and GFP fusions bind RNA in vitro. Consistent with RNA being the main binding partner for arginines in the nucleolus, we found that the same principles apply to cells from insects to man, indicating that this mechanism is highly conserved throughout evolution.

Transcription of protein-coding genes by RNA polymerase II is a repetitive, cyclic process that enables synthesis of multiple RNA molecules from the same template. The transcription cycle consists of three main stages, initiation, elongation and termination. Each of these phases is intimately coupled to a specific step in pre-mRNA processing; 5´ capping, splicing and 3´-end formation, respectively. In this article, we discuss the recent concept that cotranscriptional checkpoints operate during mRNA biogenesis to ensure that nonfunctional mRNAs with potentially deleterious effects for the cell are not produced or exported to the cytoplasm for translation.

Considering that optimal contact area and pressure at the tendon-bone interface are associated with better footprint repair and outcomes, the aim of this study was to compare the performance of standard double-row, transosseous equivalent (TOE), and partial articular supraspinatus tendon avulsion (PASTA) techniques for the treatment of full-thickness tears of the supraspinatus tendon using 3D finite element models. Loading consisted, alternately, in a preloading of 10 N and 20 N of the sutures. The footprint coverage of the standard double-row, TOE, and PASTA techniques was estimated to represent 19%, 30%, and 35%, respectively, of the repair area. The average contact pressures followed an opposite trend, i.e., the largest was estimated for the standard double-row technique, whereas the lowest was estimated for the PASTA technique. Despite the present study advancing the computational modelling of rotator cuff repair, and the results being consistent with the literature, its findings must be evaluated cautiously, bearing in mind its limitations.

Our current view of the nucleolus has been shaped by the concept that the organization of this prominent compartment within the nucleus is primarily dictated by its function, the making of ribosome subunits. Whether ribosome biogenesis is framed by a dedicated nucleolar scaffold has remained unclear. In this issue of The EMBO Journal, Caudron‐Herger and colleagues present evidence for a nucleolar skeleton composed of non‐coding RNA enriched in Alu repeat elements.

Among kinases that support the survival and turnover of tumor cells, the serine/threonine protein kinase CK2 has been shown to be frequently overexpressed or hyperactivated in solid and hematological malignancies. Our previous work on T-cell acute lymphoblastic leukemia (T-ALL) showed that CK2 maintains leukemia cell viability by phosphorylating and thereby inactivating the tumor suppressor PTEN, which results in hyperactivation of PI3K/AKT signaling. We also demonstrated the potential of using the clinical-grade CK2-specific chemical inhibitor, CX-4945 (Silmitasertib), against primary T-ALL cells. We have now extended these findings to the rare (<10% of all cases) form of T-ALL that derives from the transformation of thymocytes belonging to the γδ T-cell lineage.

Several neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), or prion diseases, are known for their intimate association with protein misfolding and aggregation. These disorders are characterized by the loss of specific neuronal populations in the brain and are highly associated with aging, suggesting a decline in proteostasis capacity may contribute to pathogenesis. Nevertheless, the precise molecular mechanisms that lead to the selective demise of neurons remain poorly understood. As a consequence, appropriate therapeutic approaches and effective treatments are largely lacking. The development of cellular and animal models that faithfully reproduce central aspects of neurodegeneration has been crucial for advancing our understanding of these diseases. Approaches involving the sequential use of different model systems, starting with simpler cellular models and ending with validation in more complex animal models, resulted in the discovery of promising therapeutic targets and small molecules with therapeutic potential. Within this framework, the simple and well-characterized eukaryote Saccharomyces cerevisiae, also known as budding yeast, is being increasingly used to study the molecular basis of several neurodegenerative disorders. Yeast provides an unprecedented toolbox for the dissection of complex biological processes and pathways. Here, we summarize how yeast models are adding to our current understanding of several neurodegenerative disorders.

The use of statins for secondary prevention in patients with peripheral (extracoronary) arterial disease is not widespread. Their possible use has only relatively recently been studied and data in the literature are sometimes controversial or are not disclosed. The aim of this paper is to review the recent literature and to discuss possible reasons for using statins in patients with extracoronary atherosclerotic arterial involvement, focusing on the areas in which they have been investigated. The main conclusions are that statins should be prescribed with the objective of reducing coronary and cerebrovascular morbidity and mortality in patients with carotid disease, abdominal aortic aneurysm and lower limb occlusive disease. There is sufficient evidence to suggest a reduction in the perioperative risk of vascular surgery when statins are used, and in patients with carotid stenosis they also appear to reduce perioperative risk in endarterectomy. Nevertheless, there are insufficient data to recommend the use of statins to control post-endarterectomy restenosis. In patients with intermittent claudication, statins improve walking distance and may be used for this purpose. Finally, there is insufficient evidence to recommend statins to prevent restenosis in lower limb revascularization procedures, to control progression of abdominal aortic aneurysms, or to reduce the severity of renal artery stenosis or renal dysfunction.

Objectives: To examine depression and suicidal behaviour and associated factors in a sample of medical students in Portugal. Methods: We conducted a cross-sectional study design of 456 native Portuguese medical students from the 4th and 5th year at the University of Lisbon. Participants answered a self-report survey including questions on demographic and clinical variables. Statistical analyses were conducted using the chi-square test, with a Monte Carlo simulation when appropriate. Results: Depression among medical students was 6.1% (n=28) and suicidal behaviour 3.9% (n=18). Higher depression scores were noted in female medical students (χ2=4.870,df=2,p=0.027), students who lived alone (χ2=8.491,df=3,p=0.037), those with poor physical health (χ2=48.269,df=2,p<0.001), with poor economic status (χ2=8.579,df=2,p=0.014), students with a psychiatric diagnosis (χ2=44.846,df=1,p=0.009), students with a family history of psychiatric disorders (χ2=5.284,df=1,p=0.022) and students with high levels of anxiety (χ2=104.8, df=3, p<0.001). Depression scores were also higher in students with suicidal ideation (χ2=85.0,df=1,p<0.001), suicidal plan (χ2=47.9,df=1,p<0.001) and suicidal attempt (χ2=19.2,df=1,p<0.001). Suicidal behaviour was higher in medical students who lived alone (χ2=16.936,df=3,p=0.001), who had poor physical health (χ2=18,929,df=2,p=0.001), poor economic status (χ2=9.181,df=2,p=0.01), who are/were in psychopharmacology treatment (χ2=30.108,df =1,p<0.001), and who had high alcohol use (χ2=7.547,df=2,p=0.023), severe depression (χ2=88.875,df=3,p<0.001) and high anxiety levels (χ2=50.343,df=3,p<0.001). The results also revealed that there were no differences between students in the 4th and 5th years of medical school regarding rate of depression and suicidal behaviour. Conclusions: Since depression and suicidal behaviour are mental health problems affecting a significant proportion of medical students, medical schools should implement programs that promote mental health wellness, physical health and economic status between other factors.

Innate immunity plays a central role in combating infections. However, the importance of innate immune sensors in detecting intracellular parasites, such as Plasmodium spp., has only recently emerged as a central topic in the field of host-pathogen interactions. Genetic dissection of innate immune pathways has uncovered a complex relationship between the host innate immune system and Plasmodium blood-stage parasites. In fact, recognition molecules of the innate immune system, such as toll-like receptors, might not only be implicated in host defense but also in the pathogenesis of the disease. Whether Plasmodium liver stage parasites are recognised and controlled by the host innate immune system remains to be discovered. In this review we discuss recent findings on how the host innate immune system may sense and fight the different forms of Plasmodium and how the latter may have evolved mechanisms to escape host detection and/or to manipulate the defensive reaction of the host.

Parkinson disease (PD)-affected brains show consistent endoplasmic reticulum (ER) stress and mitophagic dysfunctions. The mechanisms underlying these perturbations and how they are directly linked remain a matter of questions. XBP1 is a transcription factor activated upon ER stress after unconventional splicing by the nuclease ERN1/IREα thereby yielding XBP1s, whereas PINK1 is a kinase considered as the sensor of mitochondrial physiology and a master gatekeeper of mitophagy process. We showed that XBP1s transactivates PINK1 in human cells, primary cultured neurons and mice brain, and triggered a pro-mitophagic phenotype that was fully dependent of endogenous PINK1. We also unraveled a PINK1-dependent phosphorylation of XBP1s that conditioned its nuclear localization and thereby, governed its transcriptional activity. PINK1-induced XBP1s phosphorylation occurred at residues reminiscent of, and correlated to, those phosphorylated in substantia nigra of sporadic PD-affected brains. Overall, our study delineated a functional loop between XBP1s and PINK1 governing mitophagy that was disrupted in PD condition.Abbreviations: 6OHDA: 6-hydroxydopamine; baf: bafilomycin A1; BECN1: beclin 1; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CCCP: carbonyl cyanide chlorophenylhydrazone; COX8A: cytochrome c oxidase subunit 8A; DDIT3/CHOP: DNA damage inducible transcript 3; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FACS: fluorescence-activated cell sorting; HSPD1/HSP60: heat shock protein family D (Hsp60) member 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFN2: mitofusin 2; OPTN: optineurin; PD: Parkinson disease; PINK1: PTEN-induced kinase 1; PCR: polymerase chain reaction:; PRKN: parkin RBR E3 ubiquitin protein ligase; XBP1s [p-S61A]: XBP1s phosphorylated at serine 61; XBP1s [p-T48A]: XBP1s phosphorylated at threonine 48; shRNA: short hairpin RNA, SQSTM1/p62: sequestosome 1; TIMM23: translocase of inner mitochondrial membrane 23; TM: tunicamycin; TMRM: tetramethyl rhodamine methylester; TOMM20: translocase of outer mitochondrial membrane 20; Toy: toyocamycin; TP: thapsigargin; UB: ubiquitin; UB (S65): ubiquitin phosphorylated at serine 65; UPR: unfolded protein response, XBP1: X-box binding protein 1; XBP1s: spliced X-box binding protein 1.