Administration of intravenous iron formulations induces complement activation in-vivo

Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians’ choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron. Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.Conflict of Interest Statement: CG received speaking fees and research funding from Vifor Pharma

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

A serious games platform for cognitive rehabilitation with preliminary evaluation

In recent years Serious Games have evolved substantially, solving problems in diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a relevant role. Traditional cognitive therapies are often considered repetitive and discouraging for patients and Serious Games can be used to create more dynamic rehabilitation processes, holding patients' attention throughout the process and motivating them during their road to recovery. This paper reviews Serious Games and user interfaces in rehabilitation area and details a Serious Games platform for Cognitive Rehabilitation that includes a set of features such as: natural and multimodal user interfaces and social features (competition, collaboration, and handicapping) which can contribute to augment the motivation of patients during the rehabilitation process. The web platform was tested with healthy subjects. Results of this preliminary evaluation show the motivation and the interest of the participants by playing the games.- This work has been supported by FCT - Fundacao para a Ciencia e Tecnologia in the scope of the projects: PEst-UID/CEC/00319/2015 and PEst-UID/CEC/00027/2015. The authors would like to thank also all the volunteers that participated in the study

Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing [version 2; peer review: 2 approved]

Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5' end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach 'SMART-9N' and a version compatible rapid adapters  available from Oxford Nanopore Technologies 'Rapid SMART-9N'. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work

Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s) by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components) in order to ameliorate asthma-like, allergic pulmonary inflammation.</p> <p>Methods</p> <p>We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy.</p> <p>Results</p> <p>CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03). Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41). This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007) and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017). The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0.02).</p> <p>Conclusion</p> <p>Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia.</p

Validación del Nursing Activities Score en unidades de cuidados intensivos portuguesas

Objective: to describe the process of adaptation and validation of the Nursing Activities Score to the Portuguese context. Method: this was a pilot study of adaptation and validation of the Nursing Activities Score with a sample consisting of 67 patients hospitalized in the intensive care units of three Portuguese hospitals. The construct validity was assessed through factor analysis procedures and the internal consistency of the items was measured through the Cronbach’s alpha coeffi cient. Results: a mean workload value of 63.04% (SD = 14.25; Median = 61.30) was obtained. Psychometric data revealed a Cronbach’s alpha of 0.71 in the total scale, indicating an acceptable accuracy. Confi rmatory factor analysis suggested an appropriate adjustment between the model and the data (χ2 (199) = 214.5, p = 0.214; CFI = 0.95; RMSA = 0.035). Conclusion: in the present study, the Portuguese version of the Nursing Activities Score was found to be a valid instrument, enabling a safe assessment of the workload of nurses.Objetivo: descrever o processo de adaptação e validação do Nursing Activities Score para o contexto português. Método: trata-se de um estudo-piloto de adaptação e validação do Nursing Activities Score, com amostra de 67 doentes internados em unidades de cuidados intensivos de três hospitais portugueses. A validade de constructo avaliou-se mediante procedimentos de análise fatorial e a consistência interna dos itens através do coefi ciente Alpha de Cronbach. Resultados: obteve-se um valor médio da carga de trabalho de 63,04% (DP = 14,25; Mediana = 61,30). Os dados psicométricos revelaram um Alpha de Cronbach de 0,71, na escala total, indicando uma fi delidade aceitável. A análise fatorial confi rmatória sugeriu um ajustamento adequado entre o modelo e os dados (χ2(199) = 214,5, p = 0,214; CFI = 0,95; RMSA = 0,035). Conclusão: neste estudo, a versão portuguesa do Nursing Activities Score revelou-se um instrumento válido, permitindo avaliar a carga de trabalho dos enfermeiros com segurançaObjetivo: describir el proceso de adaptación y validación del Nursing Activities Score al contexto portugués. Método: estudio piloto de adaptación y validación del Nursing Activities Score, con muestra de 67 pacientes internados en unidades de cuidados intensivos de tres hospitales portugueses. La validez del constructo se evaluó mediante análisis factorial y por consistencia interna de los ítems evaluados a través del coefi ciente Alpha de Cronbach. Resultados: se obtuvo un valor medio de carga de trabajo de 63,04% (SD=14,25; Mediana=61,30). Los datos psicométricos expresaron un Alpha de Cronbach de 0,71 en la escala total, indicando fi delidad aceptable. El análisis factorial confi rmatorio sugirió un ajuste adecuado entre el modelo y os datos (χ2 (199)=214,5; p=0,214; CFI=0,95; RMSA=0,035). Conclusión: en este estudio, la versión portuguesa del Nursing Activities Score demostró ser un instrumento válido, permitiendo evaluar la carga de trabajo de los enfermeros con precisión