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Iron deficiency (ID) represents one of the most prevalent nutritional deficits, affecting almost two billion people worldwide. Gestational iron deprivation induces hypomyelination due to oligodendroglial maturation deficiencies and is thus a useful experimental model to analyze oligodendrocyte (OLG) requirements to progress to a mature myelinating state. A previous proteomic study in the adult ID brain by our group demonstrated a pattern of dysregulated proteins involved in the tricarboxylic acid cycle and mitochondrial dysfunction. The aim of the present report was to assess bioenergetics metabolism in primary cultures of OLGs and astrocytes (ASTs) from control and ID newborns, on the hypothesis that the regulation of cell metabolism correlates with cell maturation. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. ID OLGs and ASTs both exhibited decreased spare respiratory capacity, which indicates that ID effectively induces mitochondrial dysfunction. A decrease in glycogen granules was observed in ID ASTs, and an increase in ROS production was detected in ID OLGs. Immunolabeling of structural proteins showed that mitochondrial number and size were increased in ID OLGs, while an increased number of smaller mitochondria was observed in ID ASTs. These results reflect an unfavorable bioenergetic scenario in which ID OLGs fail to progress to a myelinating state, and indicate that the regulation of cell metabolism may impact cell fate decisions and maturation.

SMAD6 encodes an intracellular inhibitor of the bone morphogenetic protein (BMP) signalling pathway. Until now, SMAD6-deficiency has been associated with three distinctive human congenital conditions, i.e., congenital heart diseases, including left ventricular obstruction and conotruncal defects, craniosynostosis and radioulnar synostosis. Intriguingly, a similar spectrum of heterozygous loss-of-function variants has been reported to cause these clinically distinct disorders without a genotype–phenotype correlation. Even identical nucleotide changes have been described in patients with either a cardiovascular phenotype, craniosynostosis or radioulnar synostosis. These findings suggest that the primary pathogenic variant alone cannot explain the resultant patient phenotype. In this review, we summarise clinical and (patho)genetic (dis)similarities between these three SMAD6-related conditions, compare published Madh6 mouse models, in which the importance and impact of the genetic background with respect to the observed phenotype is highlighted, and elaborate on the cellular key mechanisms orchestrated by SMAD6 in the development of these three discrete inherited disorders. In addition, we discuss future research needed to elucidate the pathogenetic mechanisms underlying these diseases in order to improve their molecular diagnosis, advance therapeutic strategies and facilitate counselling of patients and their families.

MicroRNAs miR390-5p, miR7694-3p miR1868 and miR1849 were found to be suitable miRNA reference genes for rice, under either infection with the root-knot nematode Meloidogyne graminicola or treatment with BABA. RT-qPCR is a widely used method to investigate the expression levels of genes under certain conditions. A key step, however, to have reliable results is the normalization of expression. For every experimental condition, suitable reference genes must be chosen. These reference genes must not be affected by differences in experimental conditions. MicroRNAs are regulatory RNA molecules, able to direct the expression levels of protein coding genes. In plants, their attributed functions range from roles in development to immunity. In this work, microRNAs (miRNAs) are evaluated for their suitability as reference genes in rice after infection with root-knot nematode Meloidogyne graminicola or after priming with beta-amino butyric acid. The evaluation was based on their amplification efficiency and their stability estimates according to geNorm, NormFinder and BestKeeper. All tested miRNAs, excluding one, were considered acceptable for normalization. Furthermore, miRNAs were validated using miRNA sequencing data. The set of microRNAs miR390-5p and miR7694-3p was found to be the most stable combination under the tested conditions. Another miRNA set consisting of miR7694-3p, miR1868 and miR1849 also shows potential to be used for miRNA expression normalization under experimental conditions beyond the scope of this study. This work is the first report on reference miRNAs in rice for the purpose of plant defence studies.

In Belgium, ~ 10% of the people is estimated to suffer from allergies due to pollen emitted by the birch family trees. Timely information on forthcoming pollen exposure episodes using a forecasting system can allow patients to take preventive measures. To date, the only available information on pollen concentrations in Belgium comes from five stations that monitor daily airborne birch pollen concentrations, but real-time and detailed spatial information is lacking. Pollen transport models can both quantify and forecast the spatial and temporal distribution of airborne birch pollen concentrations if accurate and updated maps of birch pollen emission sources are available and if the large inter-seasonal variability of birch pollen is considered. Here we show that the SILAM model driven by ECMWF ERA5 meteorological data is able to determine airborne birch pollen levels using updated maps of areal fractions of birch trees, as compared to the pollen observations of the monitoring stations in Belgium. Forest inventory data of the Flemish and Walloon regions were used to update the default MACCIII birch map. Spaceborne MODIS vegetation activity combined with an updated birch fraction map and updated start and end dates of the birch pollen season were integrated into SILAM. The correlation (R2) between SILAM modelled and observed time series of daily birch pollen levels of 50 birch pollen seasons increased up to ~ 50%. The slopes of the linear correlation increased on average with ~ 60%. Finally, SILAM is able to capture the threshold of 80 pollen grains m−3 exposure from the observations.

International audience; Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.

For the first time in Belgium, fluctuations in airborne pollen quantities over a 34 years period have been analyzed. Seven pollen types have been selected comprising the most clinically relevant in Belgium nowadays (birch, alder, hazel and grasses) and others that are known to be allergenic in other European countries and frequently found in Belgium (plane, ash and mugwort). Pollen monitoring was performed with a seven-day recording volumetric spore trap placed in Brussels. We measured increasing airborne pollen for four trees, namely alder, hazel, ash and plane. Although the total pollen index for birch has not increased significantly, an increasing trend in the annual amount of days above the concentration threshold of 80 pollen grains/m3 was clearly observed. Concerning temporal variations, the pollen season has tended to end earlier for birch, ash and plane and the peak concentration of the pollen of plane has been appearing earlier in the year. In the investigated period, the pollen seasons of grasses and mugwort have tended to become less severe. Furthermore, we reported a temporal shift of the grass pollen season, beginning and ending earlier, together with an advance of the annual peak date.

This study is to investigate the efficacy of different irrigant activation techniques on removal of accumulated hard tissue debris (AHTD) in mesial roots of human mandibular molars. Extracted human mandibular molars with an isthmus between the mesial root canals were selected based on micro-CT (mu CT) scans. The mesial canals were instrumented to an apical diameter ISO30 using ProTaper rotary files. Teeth were randomly assigned to three irrigant activation groups (n = 10): ultrasonically activated irrigation (UAI) using a size 20 Irrisafe for 3 x 20 s, laser-activated irrigation (LAI) with an Er:YAG laser (2940 nm) and plain 300 mu m fiber tip inside the canal (20 mJ, 20 Hz, 3 x 20 s), and laser-activated irrigation with identical parameters with a 400 mu m photon-induced photoacoustic streaming (PIPS) tip held at the canal entrance. All teeth were scanned with mu CT before and after instrumentation and after irrigant activation. After reconstruction and image processing, the canal system volume filled with hard tissue debris before and after irrigant activation was calculated. Changes in hard tissue debris volumes were compared between groups using one-way ANOVA. The percentage volume of hard tissue debris (vol%) was significantly lower after irrigant activation in all groups. Although the lowest debris values were observed in the laser groups, no significant differences in the vol% of accumulated hard tissue debris after activation were observed between groups. Accumulated hard tissue debris was reduced significantly in all activation groups. Ultrasonically and laser-activated irrigation regimens performed similarly in this respect. None of the tested methods was able to render the root canal systems free of debris.

In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca2+ homeostasis. Among other mechanisms, these cations may affect the functionality of certain Ca2+-binding proteins and/or Ca2+ pumps. The plasma membrane calcium pump (PMCA) maintains Ca2+ homeostasis in eukaryotic cells by mediating the efflux of this cation in a process coupled to ATP hydrolysis. The aim of this work was to investigate both in vitro and in cultured cells if other divalent cations (Sr2+, Ba2+, Co2+, Cd2+, Pb2+ or Be2+) could be transported by PMCA. Current results indicate that both purified and intact cell PMCA transported Sr2+ with kinetic parameters close to those of Ca2+ transport. The transport of Pb2+ and Co2+ by purified PMCA was, respectively, 50 and 75% lower than that of Ca2+, but only Co2+ was extruded by intact cells and to a very low extent. In contrast, purified PMCA—but not intact cell PMCA—transported Ba2+ at low rates and only when activated by limited proteolysis or by phosphatidylserine addition. Finally, purified PMCA did not transport Cd2+ or Be2+, although minor Be2+ transport was measured in intact cells. Moreover, Cd2+ impaired the transport of Ca2+ through various mechanisms, suggesting that PMCA may be a potential target of Cd2+-mediated toxicity. The differential capacity of PMCA to transport these divalent cations may have a key role in their detoxification, limiting their noxious effects on cell homeostasis. Fil: Ferreira Gomes, Mariela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Mangialavori, Irene Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Ontiveros, Mallku Qhapaj. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Rinaldi, Debora Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Martiarena, Jorge Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Verstraeten, Sandra Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Rossi, Juan Pablo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina

Introduction Left atrial appendage (LAA) closure has become of major interest for patients with atrial fibrillation intolerant to oral anticoagulation therapy (OAC). Patients with a contraindication to both OAC and antiplatelet therapy are not eligible for percutaneous LAA closure. We aimed to find an alternative treatment for these specific patients. Methods From March 2014 until December 2015 five patients were referred for percutaneous LAA closure. Alternative treatment was necessary due to an absolute contraindication to OAC and antiplatelet therapy (n = 4) or after previous failed percutaneous device implantation (n = 1). A stand-alone full thoracoscopic closure of the LAA using the Atriclip PRO device (AtriCure Inc., Dayton, OH, USA) was performed under guidance of transoesophageal echocardiography (TEE). After three months all patients underwent a computed tomography scan. Mean follow-up was 7.2 months [range 4.5–9.8 months]. Results All procedures were achieved without the occurrence of complications. Complete LAA closure was obtained in all patients without any residual flow confirmed by TEE. Postoperative computed tomography confirmed persisting adequate clip positioning with complete LAA closure and absence of intracardial thrombi. During follow-up no thromboembolic events occurred. Conclusion For atrial fibrillation patients with an absolute contraindication to OAC and antiplatelet therapy a stand-alone, minimally invasive thoracoscopic closure of the LAA is a safe and feasible alternative treatment. This might be a solution to avoid serious bleeding complications while eliminating the thromboembolic risk originating from the LAA in patients who are not eligible for percutaneous LAA closure.

Het gebruik van oogdruppels is niet zonder risico’s. Hoe dien je ze het beste toe? Twee verpleegkundigen van Het Oogziekenhuis Rotterdam geven uitleg. Plus aandachtspunten bij veelvoorkomende middelen.

Steeds meer verzorgenden volgen de opleiding tot Gespecialiseerd Verzorgende Psychogeriatrie (GVP). Wat is de toegevoegde waarde van deze opleiding? ‘Ik durf de werkwijze van collega’s nu eerder ter discussie te stellen.’

Oogkwalen kunnen jeuk veroorzaken, de ogen irriteren of het zicht belemmeren. Een stoomcursus over oogproblemen bij ouderen, zodat je weet wanneer je aan de bel moet trekken.1

Veel patienten met chemo- of radiotherapie krijgen er last van: orale mucositis. Deze pijnlijke bijwerking kan verstrekkende gevolgen hebben. Door tijdige behandeling is echter veel leed te voorkomen.

Door vroegtijdige herkenning van een diabetische voet, kun je verstrekkende complicaties voorkomen. Voor wie (nog) niet vaak te maken heeft met patienten met deze zorgvraag, geeft verpleegkundig specialist en wondconsulent Mike Meuwissen antwoord op de meest gestelde vragen.

CRISPR advances genome engineering by directing endonuclease sequence specificity with a guide RNA molecule (gRNA). For precisely targeting a gene for modification, each genetic construct requires a unique gRNA. By generating a gRNA against the flippase recognition target (FRT) site, a common genetic element shared by multiple genetic collections, CRISPR-FRT circumvents this design constraint to provide a broad platform for fast, scarless, off-the-shelf genome engineering., Genome editing requires precise targeting of loci with specific gRNAs. Here the authors introduce CRISPR-FRT, which targets flippase recognition sites, common in bacterial genetic collections, for fast off-the-shelf genome engineering.