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- Microevolution of a Mycobacteroides abscessus subsp. bolletii strain in a clinical persistent infectionPublication . Santos, Andrea; Pinto, Miguel; Carneiro, Sofia; Silva, Sónia; Rodrigues, Irene; Munhá, João; Gomes, João Paulo; Macedo, RitaMycobacteroides abscessus complex (MAB), a fast-growing nontuberculous mycobacterium, is emerging as a significant infectious disease threat, due to both intrinsic and acquired resistance mechanisms to antibiotics and disinfectants and the need for extensive and multidrug regimens for treatment. Despite the prolonged regimens, outcomes are poor and persistence cases have been reported. Here, we describe clinical, microbiologic and genomic features of a M. abscessus subsp. bolletii (M. bolletii) strain consecutively isolated from a patient within an eight-year infection period. From April 2014 to September 2021, the National Reference Laboratory for Mycobacteria received eight strains isolated from a male patient. Species identification, molecular resistance profile and phenotypic drug susceptibility were determined. Five of these isolates were recovered for further in-depth genomic analysis. Genomic analysis confirmed the multidrug resistant pattern of the strain and also other genetic changes associated with adaptation to environment and defence mechanisms. We highlight the identification of new mutations in locus MAB_1881c and in locus MAB_4099c (mps1 gene), already described as associated with macrolides resistance and morphotype switching, respectively. Additionally, we also observed the emergence and fixation of a mutation in locus MAB_0364c that appeared at a frequency of 36% for the 2014 isolate, 57% for the 2015 isolate and 100% for the 2017 and 2021 isolates, clearly illustrating a fixation process underlying a microevolution of the MAB strain within the patient. Altogether these results suggest that the observed genetic alterations are a reflection of the bacterial population's continuous adaptation and survival to the host environment during infection, contributing to persistence and treatment failure.
- Indoor levels and health risk assessment of volatile organic compounds in Portuguese homesPublication . Slezakova, K.; Costa, C.; Valongo, C.; Teixeira, J.P.; Madureira, J.About indoor levels and health risk assessment of volatile organic compounds in Portuguese homes.
- Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series studyPublication . Huang, Wenzhong; Li, Shanshan; Vogt, Thomas; Xu, Rongbin; Tong, Shilu; Molina, Tomás; Masselot, Pierre; Gasparrini, Antonio; Armstrong, Ben; Pascal, Mathilde; Royé, Dominic; Sheng Ng, Chris Fook; Vicedo-Cabrera, Ana Maria; Schwartz, Joel; Lavigne, Eric; Kan, Haidong; Goodman, Patrick; Zeka, Ariana; Hashizume, Masahiro; Diaz, Magali Hurtado; De la Cruz Valencia, César; Seposo, Xerxes; Nunes, Baltazar; Madureira, Joana; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Guo, Yue Leon; Pan, Shih-Chun; Zanobetti, Antonella; Dang, Tran Ngoc; Van Dung, Do; Geiger, Tobias; Otto, Christian; Johnson, Amanda; Hales, Simon; Yu, Pei; Yang, Zhengyu; Ritchie, Elizabeth A.; Guo, YumingBackground: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. Findings: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. Interpretation: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate.
- Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series studyPublication . Huang, Wenzhong; Li, Shanshan; Vogt, Thomas; Xu, Rongbin; Tong, Shilu; Molina, Tomás; Masselot, Pierre; Gasparrini, Antonio; Armstrong, Ben; Pascal, Mathilde; Royé, Dominic; Sheng Ng, Chris Fook; Vicedo-Cabrera, Ana Maria; Schwartz, Joel; Lavigne, Eric; Kan, Haidong; Goodman, Patrick; Zeka, Ariana; Hashizume, Masahiro; Diaz, Magali Hurtado; Valencia, César De la Cruz; Seposo, Xerxes; Nunes, Baltazar; Madureira, Joana; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Guo, Yue Leon; Pan, Shih-Chun; Zanobetti, Antonella; Dang, Tran Ngoc; Dung, Do Van; Geiger, Tobias; Otto, Christian; Johnson, Amanda; Hales, Simon; Pei Yu; Yang, Zhengyu; Ritchie, Elizabeth A.; Guo, YumingBackground: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. Findings: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. Interpretation: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate.
- Effects of Zinc Oxide Nanoparticle Exposure on Human Glial Cells and Zebrafish EmbryosPublication . Valdiglesias, Vanessa; Alba-González, Anabel; Fernández-Bertólez, Natalia; Touzani, Assia; Ramos-Pan, Lucía; Reis, Ana Teresa; Moreda-Piñeiro, Jorge; Yáñez, Julián; Laffon, Blanca; Folgueira, MónicaZinc oxide nanoparticles (ZnO NPs) are among the most widely used nanomaterials. They have multiple applications in cosmetics, textiles, paints, electronics and, recently, also in biomedicine. This extensive use of ZnO NPs notably increases the probability that both humans and wildlife are subjected to undesirable effects. Despite being among the most studied NPs from a toxicological point of view, much remains unknown about their ecotoxicological effects or how they may affect specific cell types, such as cells of the central nervous system. The main objective of this work was to investigate the effects of ZnO NPs on human glial cells and zebrafish embryo development and to explore the role of the released Zn2+ ions in these effects. The effects on cell viability on human A172 glial cells were assessed with an MTT assay and morphological analysis. The potential acute and developmental toxicity was assessed employing zebrafish (Danio rerio) embryos. To determine the role of Zn2+ ions in the in vitro and in vivo observed effects, we measured their release from ZnO NPs with flame atomic absorption spectrometry. Then, cells and zebrafish embryos were treated with a water-soluble salt (zinc sulfate) at concentrations that equal the number of Zn2+ ions released by the tested concentrations of ZnO NPs. Exposure to ZnO NPs induced morphological alterations and a significant decrease in cell viability depending on the concentration and duration of treatment, even after removing the overestimation due to NP interference. Although there were no signs of acute toxicity in zebrafish embryos, a decrease in hatching was detected after exposure to the highest ZnO NP concentrations tested. The ability of ZnO NPs to release Zn2+ ions into the medium in a concentration-dependent manner was confirmed. Zn2+ ions did not seem entirely responsible for the effects observed in the glial cells, but they were likely responsible for the decrease in zebrafish hatching rate. The results obtained in this work contribute to the knowledge of the toxicological potential of ZnO NPs.
- Enhancing meat quality of weaned piglets with the dietary incorporation of Ulva lactuca and carbohydrases supplementationPublication . Pestana, José M.; Alfaia, Cristina M.; Ribeiro, David Miguel; Costa, Mónica M.; Carvalho, Daniela F.P.; Martins, Cátia F.; Alves, Victor M.D.; Lemos, José P.C.; Mourato, Miguel; Delgado, Inês; Gueifão, Sandra; Coelho, Inês; Almeida, André M.; Freire, João P.B.; Prates, José A.M.The impact of the dietary incorporation of 7% Ulva lactuca, a green seaweed, on the quality and nutritional value of piglet’s meat was assessed. U. lactuca is rich in nutrients and bioactive compounds but its cell wall is composed of complex polysaccharides that reduce their bioavailability. Therefore, the effect of supplementing piglet diets with exogenous carbohydrases was also assessed here. A total of 40 male weaned piglets were divided into four dietary groups, each with 10 piglets: control (wheat, maize and soybean meal-based diet), UL (7% U. lactuca replacing the control diet), UL +R (UL and 0.005% Rovabio®), and UL +E (UL and 0.01% ulvan lyase). The piglets were fed the diets for 2 weeks. The results showed that incorporating U. lactuca in piglet diets did not influence most of the meat quality traits (P >0.05). However, the incorporation of U. lactuca with the commercial carbohydrase (UL +R) increased the amount of the docosahexaenoic acid (DHA; 22:6n-3) in their meat (P =0.011) compared with the control, by 54%. In addition, meat from piglets fed seaweed diets showed a nearly two-fold increase in iodine contents (P <0.001). Meat tenderness, juiciness and overall acceptability of piglets fed the control diet and the UL diet were lower than those fed the diets containing seaweed and carbohydrases (P <0.001). Overall, the findings indicate that 7% U. lactuca in the diets of weaned piglets had no major detrimental effects on meat quality and their carbohydrase supplementation has the potential to improve meat sensory traits.
- Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide SequencingPublication . Latkovskis, Gustavs; Rescenko-Krums, Raimonds; Nesterovics, Georgijs; Briviba, Monta; Saripo, Vita; Gilis, Dainus; Terauda, Elizabete; Meiere, Ruta; Skudrina, Gunda; Erglis, Andrejs; Chora, Joana Rita; Bourbon, Mafalda; Klovins, JanisBackground: There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH). Methods: Whole genome sequencing with 30 coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, CYP27A1, and APOE genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for LDLR and adaptations for APOB and PCSK9 were reported. Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol 6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the LDLR gene and 1 in the APOB gene. Additionally, 24, 54, and 13 VUS were detected in LDLR, APOB, and PCSK9, respectively. No P/LP variants were identified in the other tested genes. Conclusions: Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.
- Candida auris in Intensive Care Setting: The First Case Reported in PortugalPublication . Henriques, João; Mixão, Verónica; Cabrita, Joana; Duarte, Tiago Isidoro; Sequeira, Tânia; Cardoso, Sofia; Germano, Nuno; Dias, Liliana; Bento, Luís; Duarte, Sílvia; Veríssimo, Cristina; Gomes, João Paulo; Sabino, RaquelCandida auris is an opportunistic human pathogen that has rapidly spread to multiple countries and continents and has been associated with a high number of nosocomial outbreaks. Herein, we report the first case of C. auris in Portugal, which was associated with a patient transferred from Angola to an ICU in Portugal for liver transplantation after a SARS-CoV-2 infection. C. auris was isolated during the course of bronchoalveolar lavage, and it was subjected to antifungal susceptibility testing and whole-genome sequence analysis. This isolate presents low susceptibility to azoles and belongs to the genetic clade III with a phylogenetic placement close to African isolates. Although clade III has already been reported in Europe, taking into account the patient’s clinical history, we cannot discard the possibility that the patient’s colonization/infection occurred in Angola, prior to admission in the Portuguese hospital. Considering that C. auris is a fungal pathogen referenced by WHO as a critical priority, this case reinforces the need for continuous surveillance in a hospital setting
- Safety and efficacy of the feed additive consisting of protease produced by Bacillus licheniformis DSM 33099 (ProAct 360) for use in poultry species for fattening or reared for laying/breeding (DSM Nutritional Products Ltd)Publication . EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Bampidis, Vasileios; Azimonti, Giovanna; Bastos, Maria de Lourdes; Christensen, Henrik; Dusemund, Birgit; Durjava, Mojca; Kouba, Maryline; López‐Alonso, Marta; López Puente, Secundino; Marcon, Francesca; Mayo, Baltasar; Pechová, Alena; Petkova, Mariana; Ramos, Fernando; Sanz, Yolanda; Villa, Roberto Edoardo; Woutersen, Ruud; Herman, Lieve; Louro, Henriqueta; Alija Novo, Natalia; Anguita, Montserrat; Manini, Paola; Casanova, Jordi Ortuño; Pettenati, Elisa; Pizzo, Fabiola; Brozzi, RosellaFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a protease (ProAct 360) produced by a genetically modified strain of Bacillus licheniformis (DSM 33099) as a zootechnical feed additive for poultry species for fattening or reared for laying/breeding. The production strain and its recombinant DNA were not detected in an intermediate concentrated product representative of the final formulation. The final product did not trigger a safety concern with regard to the genetic modification. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that ProAct 360 is considered safe for all growing poultry species at the recommended inclusion level of 30,000 NFP/kg complete feed. The use ProAct 360 as a feed additive did not give rise to concerns for the consumers or the environment. The additive is not an eye or a dermal irritant but should be considered a respiratory sensitiser. In the absence of data, no conclusions could be reached on the skin sensitisation potential of the additive. The FEEDAP Panel concluded that the additive has the potential to be efficacious at 30,000 NFP/kg complete feed for all poultry species for fattening or reared for laying/breeding.
- Diversity of Human T-Lymphotropic Virus Type 1 Cosmopolitan Subtype (HTLV-1a) Circulating in Infected Residents in PortugalPublication . Quina, Miriam; Ramos, Diogo; Silva, Carolina; Pádua, ElizabethHuman T-cell lymphotropic virus type 1 (HTLV-1) prevalence in Portugal is low and mainly affects immigrants from endemic areas where human immunodeficiency virus (HIV) infection represents a public health problem. Despite the majority of HTLV-1-infected individuals remains asymptomatic, severe pathologies may develop after prolonged viral persistence, namely an aggressive form of leukemia. An increased mortality rate and faster progression to death is often related to HTLV-1/HIV coinfection. Nevertheless, studies showed that some antiretrovirals used in HIV treatment lead to a positive immune response against HTLV-1. This study aimed to analyze epidemiological and clinical data, and to assess the diversity of HTLV-1 strains circulating in infected residents diagnosed in the Portuguese national reference laboratory between 2010 and 2021. Long terminal repeat and env proviral sequences derived from 20 individuals were used to generate phylogenetic trees along with multiples reference sequences from different geographic origins retrieved from the database. Three samples belong to Portuguese natives and 17 belong to immigrants: 15 from several countries of Africa, 1 from South America, and 1 from Europe; 6 patients (30%, mean age 40.3 years) showed HTLV-1-related diseases, and 6 (30%, mean age 45.2 years) were coinfected with HIV/AIDS. The results show that the Cosmopolitan subtype is circulating in Portugal, with 10 sequences being classified as subgroup A, that include Portuguese and natives from S. Tomé and Príncipe with a mean age of 39.4 years, and 10 sequences that segregated into the Senegal cluster derived from natives born in Guinea-Bissau with a mean age of 43.5 years. A high proportion of HTLV-1-related diseases and HIV/AIDS coinfection was observed. Risk behavior practices and the absence of specific control measures, including diagnostic and treatment, may contribute to a silent dissemination of a broad diversity of HTLV-1 strains and, therefore, the increased rate of progression to debilitating diseases. In this manner, an early diagnostic and a molecular surveillance of HTLV-1 transmission remains necessary in Portugal.