Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice

Mycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta 2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta 2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection

Peptidomimetic and Organometallic Derivatives of Primaquine Active against Leishmania infantum

The current treatment of visceral leishmaniasis is made difficult by the low efficacy, elevated costs, low bioavailability, and high toxicity of many of the available drugs. Primaquine, an antimalarial 8-aminoquinoline, displays activity against Leishmania spp., and several of its derivatives have been developed as potential antileishmanial drugs. However, primaquine exhibits low oral bioavailability due to oxidative deamination of its aliphatic chain. We previously developed peptidomimetic and organometallic derivatives of primaquine, with higher resistance to proteolytic degradation and oxidative deamination, which presented significant activity against primaquine-sensitive pathogens such as Plasmodium or Pneumocystis. In light of these relevant findings, we decided to evaluate these compounds against both the promastigote and intramacrophagic amastigote forms of Leishmania infantum, the agent of Mediterranean visceral leishmaniasis. We found that several of these compounds had significant activity against L. infantum. One of the peptidomimetic (3c) and one of the organometallic (7a) derivatives of primaquine were active against the clinically relevant intramacrophagic amastigote form of the parasite, causing >96% reductions in the number of amastigotes per 100 macrophages at 60 and 40 mu M, respectively, while being less cytotoxic for host cells than the reference drugs sitamaquine and miltefosine. Hence, compounds 3c and 7a represent new entries toward the development of new antileishmanial leads

Associação entre uso de hemocomponentes e mortalidade em cinco anos após transplante hepático

JUSTIFICATIVA E OBJETIVOS: A cirurgia de transplante hepático (TH) continua associada a sangramento importante em 20% dos casos, e diversos autores têm demonstrado os riscos relacionados ao uso de hemocomponentes. O objetivo deste estudo foi avaliar o impacto do uso de hemocomponentes durante toda a hospitalização na sobrevida em cinco anos de pacientes submetidos a TH. MÉTODOS: Um total de 113 pacientes submetidos ao TH foi avaliado retrospectivamente. Diversas variáveis, incluindo uso de hemocomponentes no intraoperatório e durante toda a hospitalização, foram categorizadas e avaliadas por meio de análise univariada, pelo teste de Fisher. O nível de significância adotado foi de 5%. Os resultados com p < 0,2 foram submetidos a uma análise multivariada pelo modelo de regressão logística multinominal. RESULTADOS: Doenças parenquimatosas, disfunção renal pré-operatória e maior tempo de internação no CTI e hospitalar se associaram a maior mortalidade em cinco anos após o TH (p < 0,05). Ao contrário do uso de hemocomponentes no intraoperatório, a transfusão acumulada de concentrado de hemácias, plasma fresco congelado e concentrado de plaquetas durante toda a internação hospitalar foi associada à maior mortalidade em cinco anos após o transplante de fígado (p < 0,01). CONCLUSÕES: O estudo alerta para a relação existente entre o uso de hemocomponentes durante a hospitalização e o aumento da mortalidade em cinco anos após o TH

Advances in the use of molecular tools in ecological and biodiversity assessment of aquatic ecosystems

Conservation and sustainable management of aquatic ecosystems is a priority in environmental programs worldwide. However, these aims are highly dependent on the efficiency, accuracy and cost of existent methods for the detection of keystone species and monitoring of biological communities. Rapid advances in eDNA, barcoding and metabarcoding promoted by high-throughput sequencing technologies are generating millions of sequences in a fast way, with a promising cost reduction, and overcoming some difficulties of the traditional taxonomic approaches. This paper provides an updated broad perspective of the current developments in this dynamic field presented in the special session (SS) "The use of molecular tools in ecological and biodiversity assessment of aquatic ecosystems" of the XIX Congress of the Iberian Association of Limnology (AIL2018), held in Coimbra, Portugal.Developments presented are mainly focused on the Iberian Peninsula (Portugal and Spain, including Atlantic Macaronesian islands) but include studies in France, Germany, Finland, Russia (Siberia) and South America. The networks within which these researchers are involved are yet even broader, profiting from existing molecular facilities, and traditional taxonomic expertise, which can be viewed as a characteristic of this new research area. It was evident in the SS that the use of molecular tools is widespread, being used to study a diversity of aquatic systems, from rivers' headwaters to estuaries and coastal lagoons, and volcanic, mountain and frozen lakes to hot springs. The organisms targeted are likewise varied and include fish, macroinvertebrates, meiofauna, microalgae such as diatoms and dinoflagellates, other protists, fungi, and bacteria (cyanobacteria and other). Some studies address the whole biodiversity (i.e., all species present independently of the taxonomic group) from environmental samples of water, biofilms and preservative solution from field samples (e.g., ethanol from macroinvertebrate samples). Great advances were acknowledged inWe are grateful to all participants of the special session "The use of molecular tools in ecological and biodiversity assessment of aquatic ecosystems" for the productive discussions during the AIL 2018 meeting (XIX Iberian Association of Limnology meeting in Coimbra (Portugal, June 2018). M.J. Feio is supported by MARE strategic program (UID/MAR/04292/2013); SFP Almeida is supported by GeoBioTec strategic program UID/GEO/04035/2019. R. Cordeiro was supported by a Ph.D. Grant (M3.1.a/F/017/2011) from Fundo Regional da Ciencia e Tecnologia (FRCT); A.F. Filipe and A. Garcia-Raventos were supported by FRESHING Project "Next-generation biomonitoring: freshwater bioassessment and species conservation improved with metagenomics" funded by the Portuguese Foundation for Science and Technology (FCT) and COMPETE (PTDC/AAG-MAA/2261/2014 -POCI-01-0145-FEDER-356 016824); F.M.S. Martins was supported by a FCT PhD grant (SFRH/BD/104703/2014); A.R. Calapez was supported by a grant from the FCT-PhD programme FLUVIO (PD\BD\52510\2014); A.M. Pujante acknowledges the BIOWAT-KIT_E!11892 Eurostars project; Maria Fais and Sofia Duarte were supported, respectively, by a PhD (SFRH/BD/113547/2015) and a post-doc fellowship (SFRH/BPD/109842/2015), from FCT; and C. Murria acknowledges the Fundacio Aigues de Barcelona for funding his research

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)