Biome-specific rodent dynamics and hantavirus epidemiologies in Europe

Henttonen, H., Leirs, H., Kallio, E.R., Tersago, K., Voutilainen, L

Chikungunya virus infections in Finnish travellers 2009-2019 : Infection Ecology & Epidemiology

ABSTRACT The mosquito-borne chikungunya virus (CHIKV) causes an acute febrile illness with rash, joint and muscle pain.A realtime RT-PCR assay for CHIKV detecting non-structural protein (nsP2; CHIKV nsP2-RT-qPCR) was set up. All the serodiagnosed CHIKV cases detected during 2009-2019 in Finland were screened with the assay, followed by isolations attempts and sequencing using Sanger and next generation sequencing (NGS). To validate the assay external and in-house quality control samples were used and all were correctly identified. Specificity of the assay was 100%. Assay was sensitive to detect CHIKV RNA in dilution of 10-8.During years 2009-2019 34 patients were diagnosed for acute CHIKV infection. Twelve out of 34 cases were positive by CHIKV nsP2-RT-qPCR.Two CHIKV isolations succeeded from two individuals infected originally in Thailand, 2019. From 12 CHIKV nsP2-RT-qPCR positive samples, five (42%) CHIKVs were successfully sequenced. In this study, CHIKVs from year 2019 clustered with CHIKV ECSA-lineage forming sub-cluster with strains from ones detected in Bangladesh 2017, and the ones from Jamaica (2014) within Asian lineage showing highest similarity to strains detected in Caribbean outbreak 2013-15.  Majority of the CHIKV infections detected in Finland originates from Asia and virus lineages reflect the global circulation of the pathogen.Peer reviewe

Novel pyrimidine-2,4-diamine derivative suppresses the cell viability and spindle assembly checkpoint activity by targeting Aurora kinases

Mitosis represents a clinically important determination point in the life cycle of proliferating cells. One potential drug target within the mitotic machinery is the spindle assembly checkpoint (SAC), an evolutionarily conserved signaling pathway that monitors the connections between microtubules (MTs) and chromosomes. Mistakes in SAC signaling may lead to cell division errors that can trigger elimination of cancer cells at M phase or soon after exit from mitosis. In this study, we describe the cellular effects of a novel pyrimidine-2,4-diamine derivative that we discovered to inhibit the activity of SAC. The compound caused rapid escape from the mitotic arrest induced by lack of interkinetochore tension but not by lack of MT-kinetochore attachments. In cycling cells, the compound disrupted the architecture of mitotic spindle that triggered a transient M-phase arrest that was rapidly followed by a forced mitotic exit. The premature termination of M phase was found to be a consequence of precocious inactivation of SAC caused by a direct inhibitory effect of the compound on Aurora B kinase in vitro and in cells. The compound also targets Aurora A kinase and tubulin in vitro and in cells, which can explain the observed spindle anomalies. The reduced activity of Aurora B kinase resulted in polyploidy and suppression of cancer cell viability. Our data suggest that this new pharmacophore possesses interesting anticancer properties that could be exploited in development of mitosis-targeting therapies

Metabolic engineering strategies for butanol production in Escherichia coli

The global market of butanol is increasing due to its growing applications as solvent, flavoring agent and chemical precursor of several other compounds. Recently, the superior properties of n-butanol as a biofuel over ethanol have stimulated even more interest. (Bio)butanol is natively produced together with ethanol and acetone by Clostridium species through Acetone-Butanol-Ethanol fermentation, at non-competitive, low titers compared to petrochemical production. Different butanol production pathways have been expressed in Escherichia coli, a more accessible host compared to Clostridium species, to improve butanol titers and rates.. The bioproduction of butanol is here reviewed from a historical and theoretical perspective. All tested rational metabolic engineering strategies in E. coli to increase butanol titers are reviewed: manipulation of central carbon metabolism; elimination of competing pathways; cofactor balancing; development of new pathways; expression of homologous enzymes; consumption of different substrates and molecular biology strategies. The progress in the field of metabolic modeling and pathway generation algorithms and their potential application to butanol production are also summarized here. The main goals are to gather all the strategies, evaluate the respective progress obtained, identify and exploit the outstanding challenges. This article is protected by copyright. All rights reserved.Ministério da Ciência, Tecnologia e Ensino Superior, Grant/Award Number: ERA‐IB‐2/0002/2014; Fundação para a Ciência e a Tecnologia, Grant/Award Numbers: ERA‐IB‐2/0002/2014, LISBOA¬01¬0145¬FEDER¬007660, PD/BD/52366/2013; European Commission, Grant/Award Number: H2020‐LEIT‐BIO‐2015‐1 686070–1info:eu-repo/semantics/publishedVersio

Clinical performance of a novel textile interface for neonatal chest electrical impedance tomography

Objective: Critically ill neonates and infants might particularly benefit from continuous chest electrical impedance tomography (EIT) monitoring at the bedside. In this study a textile 32-electrode interface for neonatal EIT examination has been developed and tested to validate its clinical performance. The objectives were to assess ease of use in a clinical setting, stability of contact impedance at the electrode–skin interface and possible adverse effects. Approach: Thirty preterm infants (gestational age: 30.3 ± 3.9 week (mean ± SD), postnatal age: 13.8 ± 28.2 d, body weight at inclusion: 1727 ± 869 g) were included in this multicentre study. The electrode–skin contact impedances were measured continuously for up to 3 d and analysed during the initial 20-min phase after fastening the belt and during a 10 h measurement interval without any clinical interventions. The skin condition was assessed by attending clinicians. Main results: Our findings imply that the textile electrode interface is suitable for long-term neonatal chest EIT imaging. It does not cause any distress for the preterm infants or discomfort. Stable contact impedance of about 300 Ohm was observed immediately after fastening the electrode belt and during the subsequent 20 min period. A slight increase in contact impedance was observed over time. Tidal variation of contact impedance was less than 5 Ohm. Significance: The availability of a textile 32-electrode belt for neonatal EIT imaging with simple, fast, accurate and reproducible placement on the chest strengthens the potential of EIT to be used for regional lung monitoring in critically ill neonates and infants

Effect of routine suction on lung aeration in critically ill neonates and young infants measured with electrical impedance tomography

oai:repository.mdx.ac.uk:y1752Endotracheal suctioning is a widely used procedure to remove secretions from the airways of ventilated patients. Despite its prevalence, regional effects of this maneuver have seldom been studied. In this study, we explore its effects on regional lung aeration in neonates and young infants using electrical impedance tomography (EIT) as part of the large EU-funded multicenter observational study CRADL. 200 neonates and young infants in intensive care units were monitored with EIT for up to 72 h. EIT parameters were calculated to detect changes in ventilation distribution, ventilation inhomogeneity and ventilation quantity on a breath-by-breath level 5–10 min before and after suctioning. The intratidal change in aeration over time was investigated by means of regional expiratory time constants calculated from all respiratory cycles using an innovative procedure and visualized by 2D maps of the thoracic cross-section. 344 tracheal suctioning events from 51 patients could be analyzed. They showed no or very small changes of EIT parameters, with a dorsal shift of the center of ventilation by 0.5% of the chest diameter and a 7% decrease of tidal impedance variation after suctioning. Regional time constants did not change significantly. Routine suctioning led to EIT- detectable but merely small changes of the ventilation distribution in this study population. While still a measure requiring further study, the time constant maps may help clinicians interpret ventilationmechanics in specific cases

Model selection based algorithm in neonatal Chest EIT

This paper presents a new method for selecting a patient specific forward model to compensate for anatomical variations in electrical impedance tomography (EIT) monitoring of neonates. The method uses a combination of shape sensors and absolute reconstruction. It takes advantage of a probabilistic approach which automatically selects the best estimated forward model fit from pre-stored library models. Absolute/static image reconstruction is performed as the core of the posterior probability calculations. The validity and reliability of the algorithm in detecting a suitable model in the presence of measurement noise is studied with simulated and measured data from 11 patients. The paper also demonstrates the potential improvements on the clinical parameters extracted from EIT images by considering a unique case study with a neonate patient undergoing computed tomography imaging as clinical indication prior to EIT monitoring. Two well-known image reconstruction techniques, namely GREIT and tSVD, are implemented to create the final tidal images. The impacts of appropriate model selection on the clinical extracted parameters such as center of ventilation and silent spaces are investigated. The results show significant improvements to the final reconstructed images and more importantly to the clinical EIT parameters extracted from the images that are crucial for decision-making and further interventions