Haemothorax in the course of chickenpox

Varicella pneumonia develops in 10-20% of cases of chickenpox occurring in adolescence or adult life.' Airflow obstruction, pleural effusion, and respiratory failure are less frequent. Although several haemorrhagic pleuropulmonary complications have been described in the course of chickenpox, haemothorax has been observed only once. We describe a new case of this association

Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. OBJECTIVE: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. METHODS: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. RESULTS: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. CONCLUSIONS: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies

Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma

MYC; Omomyc; MelanomaMYC; Omomyc; MelanomaMYC; Omomyc; MelanomaMYC's key role in oncogenesis and tumor progression has long been established for most human cancers. In melanoma, its deregulated activity by amplification of 8q24 chromosome or by upstream signaling coming from activating mutations in the RAS/RAF/MAPK pathway—the most predominantly mutated pathway in this disease—turns MYC into not only a driver but also a facilitator of melanoma progression, with documented effects leading to an aggressive clinical course and resistance to targeted therapy. Here, by making use of Omomyc, the most characterized MYC inhibitor to date that has just successfully completed a phase I clinical trial, we show for the first time that MYC inhibition in melanoma induces remarkable transcriptional modulation, resulting in severely compromised tumor growth and a clear abrogation of metastatic capacity independently of the driver mutation. By reducing MYC's transcriptional footprint in melanoma, Omomyc elicits gene expression profiles remarkably similar to those of patients with good prognosis, underlining the therapeutic potential that such an approach could eventually have in the clinic in this dismal disease.M.F.Z.-F. was supported by the Juan de la Cierva Programme of the Spanish Ministry of Economy and Competitiveness (IJCI-2014-22403) and Fundació La Marató de TV3 (grant 474/C/2019); F.G. was supported by Spanish Ministry of Science and Innovation Contratos Predoctorales de Formación en Investigación en Salud (PFIS; FI20/00274); I.G.-L. was supported by a grant from the University Teacher Training Program (FPU), Ministry of Universities (FPU20/04812); and S.M.-M. was supported by the Generalitat de Catalunya “Contractació de Personal Investigador Novell (FI-DGR)” 2016 fellowship (2016FI_B 00592). This project was funded by grants from the Spanish Ministry of Science and Innovation (Fondo de Inversión en Salud [FIS] PI19/01277, which also supported I.G.-L. and S.M.-M, and Retos-Colaboración 2019 RTC2019-007067-1), La Marató TV3, the Generalitat de Catalunya AGAUR 2017 grant SGR-3193, and the European Research Council (ERC-PoC II/3079/SYST-iMYC [813132]). We thank the rest of the Soucek laboratory for critical reading of the manuscript, and the personnel at Vall d'Hebron Research Institute (VHIR) High Technology Unit. We acknowledge Vall d'Hebron Institute of Oncology and the Cellex Foundation for providing research facilities and equipment

Search for Specific Biomarkers of IFNβ Bioactivity in Patients with Multiple Sclerosis

Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis

Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children. However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier mother

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

Foaming of sodium silicate-wollastonite mixtures by microwaves

[ES] Se analiza el efecto de la aplicación de las microondas durante 1,5 minutos sobre el cambio de volumen, porosidad y conductividad térmica de probetas de silicato de sodio/wollastonita. Se han estudiado mezclas con 20 a 100 % de silicato de sodio1. Se obtuvo una pérdida en masa del 19 % y un incremento de volumen del 50 % en mezclas con 20 % de silicato de sodio. A medida que el contenido de éste aumentó, la pérdida en masa se incrementó hasta 27 % y el cambio de volumen hasta en 500 % para probetas con 100 % de silicato de sodio. Se obtuvieron espumas cerámicas con porosidades totales de 65 % en probetas con 20 % de silicato de sodio (densidades aparente de 1,0 y real de 2,75 g/cc) y de 91 % en muestras con 100 % de silicato de sodio (densidades aparente de 0,182 y real de 2,0 g/cc). El tamaño de poro más uniforme se obtuvo para contenidos del 80 % de silicato de sodio (10 a 30 μm). Las conductividades térmicas de las espumas cerámicas fueron de 0,2, 0,125 y 0,065 W/m·K para contenidos de 40, 70 y 100 % de silicato de sodio, respectivamente.[EN] The effect of the application of microwaves on the volume, porosity and thermal conductivity of sodium silicate-wollastonite mixtures was studied. The compositional range studied was 20-100 wt% sodium silicate. A weight loss of 19% and a volume increase of 50% were obtained for mixtures with 20 wt% sodium silicate. The weight loss increased up to 27% with increasing sodium silicate content. Volume increased in 500% for samples with 100 wt% sodium silicate. Ceramic foams with total porosities of 65 vol % were obtained for specimens containing 20 wt% sodium silicate (with apparent and real densities of 1.0 and 2.75 g/cc, respectively), while samples containing 100 wt% sodium silicate presented total porosities of 91 vol% (with apparent and real densities of 0.182 and 2.0 g/cc, respectively). The best pore size uniformity (10-30 μm) was obtained for a sodium silicate content of 80 wt%. The thermal conductivities of the ceramic foams were 0.2, 0,125 and 0,065 W/m·K for sodium silicate contents of 40, 70 and 100 wt%, respectively.Peer reviewe

Hydrophilic interaction liquid chromatography coupling with electrospray ionization mass spectrometry (HILIC-ESI-MS) for lanthanide speciation in nuclear fuel treatment processes

International audienc

Étude de la spéciation exhaustive des lanthanides et des actinides pour les procédés de traitement du combustible nucléaire : approche intégrée par spectrométrie de masse

International audienc