Efeito da combinação de stressores químicos e naturais em Daphnia magna

Mestrado em Toxicologia e EcotoxicologiaA contaminação ambiental é quase sempre caracterizada pela combinação de factores de stress de várias origens (biológica, química e física). Na agricultura, a grande diversidade de colheitas e das pestes que as atingem, conduz à utilização de diversos tipos de tratamentos e à aplicação de uma larga diversidade de produtos químicos. O fungicida carbendazim, pertencente ao grupo dos benzimidazóis, e é um dos mais utilizados em todo o mundo, enquanto que o insecticida organofosforado clorpirifos, também globalmente utilizado, é somente o mais vendido em Portugal. Igualmente, da actividade industrial advêm alguns dos mais frequentes contaminantes encontrados nos nossos ecossistemas. Os metais pesados, como o cádmio e o níquel, resultantes de actividades mineiras e metalúrgicas, são importantes agentes de toxicidade, uma vez que induzem vários tipos de efeitos nocivos. O fenómeno das alterações climáticas, que já se faz sentir e que irá intensificar-se nas próximas décadas, levando ao surgimento de condições ambientais extremas durante longos períodos de tempo, será também uma nova fonte de agentes stressores que importa ter em consideração. A Avaliação do Risco Ecológico (ARE) tem como objectivo avaliar a probabilidade de determinados efeitos ecológicos adversos ocorrerem como resultado da exposição a um ou mais stressores (U.S.EPA 1992). Uma nova abordagem baseada na avaliação dos efeitos cumulativos da toxicidade resultante da acção de múltiplos stressores surgiu nos últimos anos, levando ao desenvolvimento de novas ferramentas para descrever e analisar os efeitos das misturas. Os modelos teóricos utilizados na avaliação da toxicidade de misturas são baseados nos conceitos de adição de concentração (AC) e acção independente (AI) e têm sido recentemente aplicados por diversos autores. No entanto, têm vindo a ser observados desvios a estes dois modelos conceptuais, principalmente devido a interacções que podem ocorrer ao nível toxicocinético ou toxicodinâmico e produzir padrões de resposta diferentes; sinergismo onde os efeitos são mais severos; antagonismo com efeitos menos severos; dependentes do nível da dose ou do rácio entre os dois componentes da mistura. A avaliação dos efeitos dos contaminantes em organismos aquáticos inclui geralmente a avaliação de parâmetros agudos (mortalidade) e crónicos, como a reprodução, o crescimento e a actividade alimentar. O cladócero, Daphnia magna tem sido utilizado, durante muitos anos, em ensaios de toxicidade devido à sua elevada sensibilidade, fácil manuseamento e manutenção em cultura e ainda pela sua alta taxa reprodutiva. Este trabalho tem como principais objectivos: avaliar a toxicidade de misturas heterogéneas, compostas por metais (Cd e Ni) e pesticidas com modos de acção ambíguos e diferente natureza química (carbendazim e clorpirifos); avaliar a toxicidade resultante da introdução de stressores naturais (temperatura e oxigénio dissolvido) em combinação com os diferentes químicos; obter padrões de comportamento das misturas em função dos conceitos de adição de concentração (AC) e acção independente (AI) e verificar a ocorrência de desvios (sinergismo, antagonismo e dependência da dose ou do rácio da mistura); verificar a existência de sinergismos associados às condições extremas de temperaturas altas e de hipoxia e avaliar a adequação dos modelos AI e AC na interpretação do comportamento da toxicidade conjunta de stressores com modos de acção diferentes ou semelhantes. Este estudo é um excelente exemplo da diversidade de efeitos e comportamentos que podem resultar da combinação de tóxicos bastante comuns no nosso ambiente, uma vez que todos os possíveis desvios aos modelos ocorreram (sinergismo, antagonismo, dependência da dose ou do rácio da mistura). Verificaram-se alterações de efeitos sinergísticos para efeitos antagonísticos, respectivamente, de exposições letais para subletais, em praticamente todas as misturas ajustadas ao modelo de acção independente. Os efeitos sinergísticos normalmente associados a condições ambientais extremas como altas temperaturas e baixas concentrações de oxigénio dissolvido foram observados nas exposições agudas, a partir de ajustes ao modelo de acção independente. O modelo matemático aqui utilizado e mostrou ser no geral, uma boa ferramenta na avaliação de respostas dadas pela D. magna exposta a misturas binárias. A validação a partir de estudos toxicocinéticos e toxicodinâmicos parece ser de primordial importância para este tipo de avaliações, uma vez que permitirá compreender todos os processos fisiológicos envolvidos na complexidade das misturas.Environmental contamination is often characterised by the combination of stress factors of various sources (biological, chemical and physical). In agriculture, the diversity of crops and respective pests lead to the use of a large variety of treatments and to the application of a wide miscellaneous of chemical compounds. Carbendazim, a benzimidazole fungicide, is one of the most used pesticides in all world, while chlorpyrifos, an organophosphorus insecticide, also widely used is the most sold insecticide in Portugal. Also, from the industrial activity, many compounds that are manufactured can be usually found in our ecosystems. Heavy metals, such as cadmium and nickel, resulting from metallurgic and mining activities, are one of those chemicals and are considered important toxic agents for inducing several types of harmful effects. Climate changes phenomenon can increase adverse effects during the next decades, leading to the emergence of extreme environmental conditions during long time periods, and will also be a source of stressors that should be taken into consideration. Ecological risk assessment (ERA) has as main objective to assess the likelihood of occurrence of adverse ecological effects as a result of exposure to single or multiple stressors. A new approach based on the evaluation of cumulative effects resulting from the toxicity of the multiple stressors action emerged in the last few years, conducting to the development of novel tools to describe and analyse mixtures effects. Theoretical models based on the two widely concepts used on toxicity of mixtures, concentration addition (CA) and independent action (IA), have been recently applied by several authors. Deviations from these two conceptual models have also been observed, probably due to interactions that may occur at toxicokinetics or toxicodynamics levels and produce different behaviour patterns, according to a more severe effect (synergism), less severe effect (antagonism), dose level or dose ratio dependent. An evaluation of the contaminants effects in aquatic organisms usually includes assessment of acute and sublethal parameters such as mortality and feeding activity, respectively. Daphnia magna has been used during many years in standard toxicity tests due to its high sensitivity, easy handling and high reproductive rate. The main objectives of this study are: to evaluate the toxicity of heterogeneous mixtures of metals (Cd and Ni) and pesticides with ambiguous modes of action and different chemical nature (carbendazim and chlorpyrifos); to evaluate the toxicity of natural stressors (temperature and dissolved oxygen) in combination with the different chemicals; to obtain behaviour patterns as a function of CA and IA concepts and verify the occurrence of possible deviations (synergism, antagonism, dose level dependent and dose ratio dependent); to check the occurrence of synergisms associated to extreme conditions of high temperatures and hypoxia and to evaluate the adequacy of the IA and CA models on the interpretation of the joint toxicity behaviour of chemicals with dissimilar or similar modes of action. This work comprises a diversity of effects and behaviours that can result from the combination of very common toxicants once all the possible deviations have occurred (synergism, antagonism, dose level and dose ratio dependency). A switch from synergistic to antagonistic effects has occurred from lethal to sublethal exposures, in practically all the mixtures fitted to IA model. Synergistic effects normally associated to extreme environmental conditions such as high temperatures and low dissolved oxygen levels were observed on acute exposures, after the fit to IA model. The mathematical model used in this work showed to be, in general, a good tool to evaluate the responses given by the exposure of D. magna to binary mixtures. Validation from toxicokinetics and toxicodynamics studies seems to be of crucial importance for this kind of approach, once it permits the understanding of toxicological pathways involved on complex mixtures

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use