What every Intensivist should know about the role of ammonia in liver failure

Publisher Copyright: © 2023 The AuthorsPurpose: Acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) patients have high short-term mortality and morbidity. In the context of liver failure, increased serum ammonia is associated with worse neurological outcomes, including high-grade hepatic encephalopathy (HE), cerebral edema, and intracranial hypertension. Besides its neurotoxicity, hyperammonemia may contribute to immune dysfunction and the risk of infection, a frequent trigger for multi-organ failure in these patients. Material and methods: We performed a literature-based narrative review. Publications available in PubMed® up to June 2023 were considered. Results: In the ICU management of liver failure patients, serum ammonia may play an important role. Accordingly, in this review, we focus on recent insights about ammonia metabolism, serum ammonia measurement strategies, hyperammonemia prognostic value, and ammonia-targeted therapeutic strategies. Conclusions: Serum ammonia may have prognostic value in liver failure. Effective ammonia targeted therapeutic strategies are available, such as laxatives, rifaximin, L-ornithine-L-aspartate, and continuous renal replacement therapy.proofepub_ahead_of_prin

Água e saúde: análise do risco da presença de trihalometanos na água para consumo humano

A aplicação de compostos clorados e do ozono na desinfeção da água trouxe enormes benefícios para a preservação da saúde pública, através da obtenção duma água bacteriologicamente segura para consumo humano. Contudo estes compostos podem induzir a formação de subprodutos da desinfeção (SPD) com efeitos cancerígenos e mutagénicos comprovados. Neste trabalho apresenta-se uma síntese do estudo sobre a ocorrência de trihalometanos na água distribuída, realizado nos 14 municípios do distrito de Braga (Portugal), visando a avaliação do risco de cancro (RC) e do risco de efeitos não carcinogénicos (RENC) através do método proposto pela USEPA e IRIS. Num cenário gravoso, o RC deu um valor superior ao limite máximo definido como negligenciável, em todos os municípios analisados, sendo a ingestão a via de exposição mais relevante. O resultado do RENC foi quase sempre inferior à unidade indicando um nível de risco aceitável. O uso de indicadores do risco para a saúde pode constituir uma ferramenta útil quer no apoio à decisão das entidades gestoras de sistemas de abastecimento de água, quer na definição de estratégias e políticas de saúde pública que visem a mitigação deste risco de modo a preservar/aumentar a qualidade de vida das populações

Artificial seaweed substrates complement ARMS in DNA metabarcoding-based monitoring of temperate coastal macrozoobenthos

We used DNA metabarcoding to compare macrozoobenthic species colonization between autonomous reef monitoring structures (ARMS) and artificial seaweed monitoring systems (ASMS). We deployed both substrates in two different locations (Ría de Vigo and Ría de Ferrol, NW Iberian coast) and collected them after 6, 9, and 12 months to assess species composition of the colonizing communities through high-throughput sequencing of amplicons within the barcode region of the mitochondrial cytochrome c oxidase I (COI-5P) and the V4 domain of the 18S rRNA genes. We observed a consistently low similarity in species composition between substrate types, independently of sampling times and sites. A large fraction of exclusive species was recorded for a given substrate (up to 72%), whereas only up to 32% of species were recorded in both substrates. The shape and structural complexity of the substrate strongly affected the colonization preferences, with ASMS detecting more exclusive crustacean and gastropod species and a broader diversity of taxonomic groups (e.g., Entoprocta and Pycnogonida were detected exclusively in ASMS). We demonstrate that despite the customary use of ARMS for macrozoobenthos monitoring, by using ASMS we complemented the recovery of species and enlarged the scope of the taxonomic diversity recorded.This study was supported by the project ATLANTIDA (NORTE-01-0145-FEDER-000040), funded by Programa Operacional Regional do Norte (NORTE2020) and by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. (Foundation for Science and Technology). Financial support granted by the FCT to BRL (PD/BD/127994/2016) and SD (CEECIND/00667/2017) is also acknowledged.We would like to thank all the members of the Marine Biology Station of A Graña and all the members of the ECIMAT Marine Station for providing the resources and support during sampling campaigns. We also acknowledge the two anonymous reviewers for their valuable comments

Cooperação internacional em educação militar como um instrumento de política de defesa e inserção do Brasil na América Central

Brazilian cooperation has grown since the beginning of the 21st century. It contributed to the conquest of political prestige, economic expansion, and promotion of development, especially in Latin America and Africa. However, only a few studies have analyzed how international cooperation can influence political articulation with other countries, mainly in the defense area. The present analysis of Brazilian cooperation in military education with Central American countries since 1995 intends to show how international cooperation policies are relevant and efficient instruments of Brazilian defense policy, not only as foreign policy tools. This study uses documentary and bibliographic research besides interviews with Central American officers to obtain this conclusion. The article shows how Brazil uses military education cooperation to achieve its national defense objectives by influencing positively Central American military leaders.A cooperação internacional brasileira cresceu no início do século XXI, contribuindo para a conquista de prestígio político, expansão econômica e promoção de desenvolvimento, especialmente no seu entorno estratégico. Contudo, faltam pesquisas direcionadas para estudar como a cooperação internacional pode ser usada para incidir na articulação política com outros países no campo da defesa. Analisando a cooperação brasileira em educação militar com os países da América Central a partir de 1995, este artigo busca demonstrar como atividades de cooperação internacional são instrumentos relevantes e efetivos da política de defesa do Brasil, além de ferramentas de política externa. Para chegar a essa conclusão, foi realizada uma extensa pesquisa documental e bibliográfica, bem como entrevistas com militares centro-americanos. O presente artigo pretende, assim, expressar ao leitor a capacidade da cooperação internacional brasileira em educação militar de incidir politicamente nos países da América Central, o que pode facilitar a consecução dos objetivos elencados na Política Nacional de Defesa do Estado brasileiro

Cooperação internacional em educação militar como um instrumento de política de defesa e inserção do Brasil na América Central

Brazilian cooperation has grown since the beginning of the 21st century. It contributed to the conquest of political prestige, economic expansion, and promotion of development, especially in Latin America and Africa. However, only a few studies have analyzed how international cooperation can influence political articulation with other countries, mainly in the defense area. The present analysis of Brazilian cooperation in military education with Central American countries since 1995 intends to show how international cooperation policies are relevant and efficient instruments of Brazilian defense policy, not only as foreign policy tools. This study uses documentary and bibliographic research besides interviews with Central American officers to obtain this conclusion. The article shows how Brazil uses military education cooperation to achieve its national defense objectives by influencing positively Central American military leaders.A cooperação internacional brasileira cresceu no início do século XXI, contribuindo para a conquista de prestígio político, expansão econômica e promoção de desenvolvimento, especialmente no seu entorno estratégico. Contudo, faltam pesquisas direcionadas para estudar como a cooperação internacional pode ser usada para incidir na articulação política com outros países no campo da defesa. Analisando a cooperação brasileira em educação militar com os países da América Central a partir de 1995, este artigo busca demonstrar como atividades de cooperação internacional são instrumentos relevantes e efetivos da política de defesa do Brasil, além de ferramentas de política externa. Para chegar a essa conclusão, foi realizada uma extensa pesquisa documental e bibliográfica, bem como entrevistas com militares centro-americanos. O presente artigo pretende, assim, expressar ao leitor a capacidade da cooperação internacional brasileira em educação militar de incidir politicamente nos países da América Central, o que pode facilitar a consecução dos objetivos elencados na Política Nacional de Defesa do Estado brasileiro

Placebo response in chronic peripheral neuropathic pain trials: systematic review and meta-analysis

Objective: To estimate the magnitude of the placebo and nocebo responses in chronic peripheral neuropathic pain (CNP) and explore possible associations with trial characteristics. // Methods: We searched CENTRAL, MEDLINE, and Embase for randomized controlled trials (RCTs) from inception to May 2020. We included placebo-controlled RCTs of ≥8 weeks investigating first-line pharmacological interventions for CNP. Primary endpoints were the placebo response, the proportion of patients receiving placebo with pain intensity reduction (PIR) ≥30% from baseline, and the nocebo response, the proportion of patients receiving placebo experiencing adverse events (AEs). Screening, data extraction, and bias assessment (with the Cochrane risk of bias tool) were conducted by independent reviewers. We pooled data using a random-effects model. // Results: We included 50 trials, with a combined 5,693 participants allocated to placebo, conducted between 1998 and 2020. Overall, 38% of patients receiving placebo reported PIR≥30% (95% CI 34 to 42, I2=86%); 23% reported PIR≥50% (95% CI 20 to 26; I2=81%). 50% of patients receiving placebo reported AEs (95% CI 0.43 to 0.58; I2=97%); 2% reported serious AEs (95% CI 2 to 3; I2=58%). In patients receiving active interventions, the placebo response accounts for 75% of the treatment effect on PIR≥30%, and the nocebo response accounts for 75% of the AEs. Interpreted inversely, only 25% of responses and 25% of adverse events can be attributed to the intervention. Publication year positively correlated with PIR≥30% and negatively correlated with AEs. Female sex negatively correlated with AEs. // Conclusions: The placebo and nocebo responses in parallel-designed RCTs in CNP are substantial and should be considered in trial interpretation and in the design of future trials

Bayesian methods to analyze historical collections in time and space: a case study using Cabo Verde endemic flora

Original ResearchBiological collections, including herbarium specimens, are unique sources of biodiversity data presenting a window on the history of the development and accumulation of knowledge of a specific geographical region. Understanding how the process of discovery impacts that knowledge is particularly important for oceanic islands which are often characterized by both high levels of endemic diversity and high proportions of threatened taxa. The archipelagos of the Macaronesian region (i.e. Azores, Canaries, Savages, Madeira, and Cabo Verde) have been the focus of attention for scientific expeditions since the end of the 17th century. However, there is no integrated study describing the historical process of collecting, discovery and description of its flora. Using as a case study the Cabo Verde endemic angiosperm flora, we review the history of collecting in the flora and apply a Bayesian approach to assess the accumulation of species discovery, through time and space across the nine islands of the archipelago. Our results highlight the central role not only of natural characteristics (e.g. area, age, maximum altitude and average value of the terrain ruggedness index) but also historical factors (i.e. the location of major harbors) for the development of knowledge of the flora. The main factors that have determined the process of species description in the archipelago and how this impact our understanding of diversity patterns across archipelagos are discussedinfo:eu-repo/semantics/publishedVersio

A synthetic biology approach to engineer "therapeutic" bacteria

The high incidence and mortality of solid tumors like breast cancer makes the development of novel therapeutic agents a high priority. Curcumin, a natural substance from the rhizome of Curcuma longa, has captured the attention of the scientific community. Pre-clinical trials and extensive research has demonstrated its ability to prevent cancer. Indeed, curcumin has been shown to target critical genes involved in angiogenesis, apoptosis, cell cycle and metastasis, and consequently to inhibit cell growth. Currently, the clinical use of curcumin is mainly limited by its poor bioavailability which implies repetitive oral doses in order to achieve the therapeutic concentrations inside the cell. The idea of the present work is to design a strategy that could link the common technique used to treat solid tumors (ultrasound) with the therapeutic effects of curcumin. The plan is to use the temperature increase (consequence of ultrasound treatment) to trigger the in situ expression of curcumin by engineered bacteria. Escherichia coli was chosen as the model organism in which the genes involved in the curcumin pathway will be cloned. Those genes (4-coumarate: CoA ligase, diketide-CoA synthase and curcumin synthase) were successfully cloned under the control of a temperature sensitive promoter (dnaK). The proof-of-concept that the dnaK promoter can be induced by a temperature increase, leading to the expression of the 3 necessary genes, is currently being tested, using several biochemical assays. Moreover, several knockouts (KO) of specific genes from the E. coli K-12 MG1655 genome were performed in order to maximize the production of curcumin. The deletion strategy, as well as the definition of the non-essential genes to be KO, was determined in silico. This strategy included one single KO (gnd gene) and the multiple KO of five non-essential genes for aerobic growth (fumA, fumB, fumC, ccmA and argO) and serA gene for anaerobic growth. After optimizing the genes expression under the control of the temperature inducible promoter, the several KO will be transformed with this construction to confirm the improvement of curcumin production

Meiofauna metabarcoding in Lima estuary (Portugal) suggests high taxon replacement within a background of network stability

Meiofauna organisms play an important role in ecological and sedimentary processes in estuarine ecosystems. Recently, the application of environmental DNA (eDNA) for investigating meiofauna in different environments, improved the accessibility to its diversity and composition in a scale, frequency and depth previously unattainable. Nevertheless, little attention has been given to the description of baseline patterns of coupled spatial and temporal dynamics of meiobenthic communities. In an earlier study conducted in Lima estuary (NW Portugal), using eDNA metabarcoding of sediment samples, high levels of meiofauna Operational Taxonomic Units (OTUs) turnover were recorded, between sampling points only a few metres apart, and among sampling stations along the estuary. In order to verify the consistency of these patterns, in the current study we re-assessed Lima estuary's meiofauna communities approximately 1 year after, applying the same methodological approach (targeting segments of the COI and 18S rRNA genes), and expanding HTS-data analyses through the use of association networks. A high degree of spatial turnover was found both within and between sampling stations and this was consistent for both markers and years. As a consequence, most of the beta-diversity was accounted by OTU replacement with only a minor contribution from OTU richness. Despite the high levels of OTU replacement, relatively stable network properties were found in meiofaunal communities, irrespective of the sampled year. Network properties appear to shift sharply from the downstream/high salinity area of the estuary to the mesohaline medium-upstream areas, suggesting high resilience and redundancy of meiofaunal communities along the estuarine gradient. The recognition of meiofauna's networks features may improve the understanding of the ecology and dynamics of these communities that apparently hold large portions of variable elements, thereby making difficult their analyses solely based on the OTU/species composition.This study was funded by the project "The NextSea: Next generation monitoring of coastal ecosystems in a scenario of global change'' (operacao NORTE-01-0145-FEDER-000032), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Maria Fais and Sofia Duarte were supported, respectively by a Ph.D. (SFRH/BD/113547/2015) and a post-doc fellowship (SFRH/BPD/109842/2015) from FCT. The authors would like to thank Prof. Jesus Troncoso (University of Vigo) and Prof. Pedro Gomes (University of Minho) for their availability and hospitality for the lab processing; Dr. Bruno Sampieri and Barbara Leite (University of Minho) for the great support during the implementation of the practical stage of the research. The authors would like also to thank the anonymous reviewers for critically reading the manuscript and suggesting substantial improvements

Hydrophobic DES Based on Menthol and Natural Organic Acids for Use in Antifouling Marine Coatings

Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Marine biofouling negatively impacts industries with off-shore infrastructures, such as naval, oil, and aquaculture. To date, there are no ideal sustainable, economic, and environmentally benign solutions to deal with this phenomenon. The advances achieved in green solvents, as well as its application in different industries, such as pharmaceutical and biotechnology, have promoted the emergence of deep eutectic systems (DES). These eutectic systems have applications in various fields and can be revolutionary in the marine-based industrial sector. In this study, the main objective was to investigate the potential use of hydrophobic DES (HDES) based on menthol and natural organic acids for their use as marine antifouling coatings. Our strategy encompassed the physicochemical characterization of different formulations, which allowed us to identify the most appropriate molar ratio and intermolecular interactions for HDES formations. The miscibility of the resulting HDES with the marine coating has been evaluated and proven to be successful. The Men/OL (1:1) system proved to be the most promising in terms of cost-production and thus was the one used in subsequent antifouling tests. The cytotoxicity of this HDES was evaluated using an in vitro cell model (HaCat cells) showing no significant toxicity. Furthermore, the application of this system incorporated into coatings that are used in marine structures was also studied using marine species (Mytilus edulis mussels and Patella vulgata limpets) to evaluate both their antifouling and ecotoxicity effects. HDES Men/OL (1:1) incorporated in marine coatings was promising in reducing marine macrofouling and also proved to be effective at the level of microfouling without viability impairment of the tested marine species. It was revealed to be more efficient than using copper oxide, metallic copper, or ivermectin as antifouling agents. Biochemical assays performed on marine species showed that this HDES does not induce oxidative stress in the tested species. These results are a strong indication of the potential of this HDES to be sustainable and efficiently used in marine fouling control technologies.publishersversionpublishe