Hepatic Complications

Peer reviewe

Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma in Asia Frequently Shows SETD2 Alterations.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary T-cell lymphoma of the digestive tract derived from intraepithelial lymphocytes and characterized by an aggressive clinical course. In this study, nine cases of Japanese MEITL were analyzed by targeted Next Generation Sequencing (NGS) and immunohistochemistry and were integrated with previously reported whole-genome copy number microarray-based assay data. The highlight of our findings is that all cases showed alterations of the tumor suppressor gene SETD2 by mutations and/or loss of the corresponding 3p21 locus. We also demonstrated that all cases showed mutations in one or more genes of JAK/STAT pathway. Therefore, the combination of epigenetic deregulation and cell signaling activation represent major oncogenic events in the pathogenesis of MEITL in Asian MEITL, similar to Western MEITL

Usefulness of multiparametric computerized tomography findings in the differential diagnosis of stroke mimics of epileptic origin: A preliminary study

Objetivo: Tras la activación del código ictus, hasta un 30% de los pacientes presentan cuadros imitadores del ictus, siendo la epilepsia el más frecuente. Evaluamos la utilidad de la TC cerebral multiparamétrica para la diferenciación de los déficit de origen comicial versus vascular. Material y métodos: Estudio observacional retrospectivo con recogida prospectiva de datos. Se revisan imágenes de TC multiparamétrica de pacientes atendidos como código ictus durante un año que finalmente fueron diagnosticados de etiología comicial. Resultados: N = 11 (varones 36%, edad media 74,5 a˜nos). Tres pacientes presentaban focalidad neurológica derecha, 4 focalidad izquierda y 4 afasia aislada. El tiempo máximo desde el inicio de la clínica hasta la realización de la TC multiparamétrica fue de 8,16 h. La TC perfusión fue normal en 2 pacientes. Nueve pacientes mostraron alargamiento/acortamiento del tiempo al pico (Tmáx), siendo los mapas de flujo y volumen variables. El electroencefalograma se realizó con un tiempo máximo de evolución desde el inicio de la clínica de 47,6 h. Cuatro registros mostraron hallazgos compatibles con estatus epiléptico, 2 actividad epileptiforme focal y los 5 restantes lentificación poscrítica ipsolateral a las anomalías de la TC perfusión. Conclusión: El alargamiento del tiempo al pico en una distribución cortical multilobar en ausencia de oclusión de gran vaso y con respeto de ganglios de la base ha resultado el parámetro más sensible para la diferenciación de estas entidades en nuestra serie. Consideramos que la TC cerebral multiparamétrica es una herramienta rápida, disponible y útil para el diagnóstico diferencial de síntomas neurológicos deficitarios de inicio brusco debidos a etiología comicial que son atendidos como código ictus.Objective: Thirty percent of the patients for whom code stroke is activated have stroke mimics, the most common being epilepsy. Our purpose was to evaluate the usefulness of multiparametric CT for differentiating between seizure-related symptoms and vascular events. Material and methods: We conducted a retrospective observational study; data were gathered prospectively during one year. We studied multiparametric CT images of patients admitted following code stroke activation and finally diagnosed with epilepsy. Results: The study included a total of 11 patients; 36% were men and mean age was 74.5 years. Three patients had right hemisphere syndrome, 4 displayed left hemisphere syndrome, and the remaining 4 had isolated aphasia. Maximum time from symptom onset to multiparametric CT study was 8.16 hours. Perfusion CT results were normal in 2 patients. Nine patients showed longer or shorter times to peak (Tmax); cerebral blood volume (CBV) and cerebral blood flow (CBF) maps varied. EEG was performed a maximum of 47.6 hours after symptom onset. Four patients showed findings compatible with status epilepticus, 2 displayed focal epileptiform activity, and 5 showed post-ictal slowing ipsilateral to perfusion CT abnormalities. Conclusion: The most sensitive parameter for differentiating between stroke and epilepsy in our series was increased time to peak in multilobar cortical locations in the absence of largevessel occlusion and basal ganglia involvement. Multiparametric CT is a fast, readily available, and useful tool for the differential diagnosis of acute-onset neurological signs of epileptic originin patients initially attended after code stroke activatio

Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.

Reliable, non-invasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected six proteins [L-Ficolin, vascular-cell-adhesion-molecule-1 (VCAM1), tissue-inhibitor of metalloproteinase-1, von Willebrand factor, intercellular-adhesion-molecule-1, and CD97] based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these six proteins and five selected from the literature [suppression of tumorigenicity-2 (ST2), angiopoietin-2 (ANG2), hyaluronic acid (HA), thrombomodulin, and plasminogen activator inhibitor-1] in samples from 80 patients. The results demonstrate that together ST2, ANG2

Measuring for change : A multi-centre pre-post trial of an air quality feedback intervention to promote smoke-free homes

Second-hand smoke exposure in the home is a serious cause of ill-health for children. Behaviour change interventions have been developed to encourage parents to keep homes smoke-free. This study evaluates a novel air quality feedback intervention using remote air quality monitoring with SMS and email messaging to promote smoke-free homes among families from deprived areas. This paper presents a pre-post study of this intervention. Using internet connected monitors developed with the Dylos DC1700, daily SMS and weekly email feedback provided for 16 days to participants recruited in four European countries. Participants were recruited based on their stage of change, in order to target those most able to achieve smoke-free homes. The primary outcome measure was median change in mean fine particulate matter (PM) concentration between baseline and follow-up periods, while secondary outcome measures included change in time over the World Health Organisation (WHO) guideline limit for PM exposure over 24 h (25 µg/m) in those periods and the number of homes where PM concentrations reduced. Telephone interviews were conducted with participants in Scotland post-intervention to explore intervention experience and perceived effectiveness. Of 86 homes that completed the intervention study, 57 (66%) experienced pre-post reductions in measured PM. The median reduction experienced was 4.1 µg/m (a reduction of 19% from baseline, p = 0.008). Eight homes where concentrations were higher than the WHO guideline limit at baseline fell below that level at follow-up. In follow-up interviews, participants expressed positive views on the usefulness of air quality feedback. Household air quality monitoring with SMS and email feedback can lead to behaviour change and consequent reductions in SHS in homes, but within the context of our study few homes became totally smoke-free

Marker-free image registration of electron tomography tilt-series

<p>Abstract</p> <p>Background</p> <p>Tilt series are commonly used in electron tomography as a means of collecting three-dimensional information from two-dimensional projections. A common problem encountered is the projection alignment prior to 3D reconstruction. Current alignment techniques usually employ gold particles or image derived markers to correctly align the images. When these markers are not present, correlation between adjacent views is used to align them. However, sequential pairwise correlation is prone to bias and the resulting alignment is not always optimal.</p> <p>Results</p> <p>In this paper we introduce an algorithm to find regions of the tilt series which can be tracked within a subseries of the tilt series. These regions act as landmarks allowing the determination of the alignment parameters. We show our results with synthetic data as well as experimental cryo electron tomography.</p> <p>Conclusion</p> <p>Our algorithm is able to correctly align a single-tilt tomographic series without the help of fiducial markers thanks to the detection of thousands of small image patches that can be tracked over a short number of images in the series.</p

The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

BACKGROUND: RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants.  RESULTS: Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway.  CONCLUSION: This work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M. circinelloides during exponential and stationary growth phases and opens up an important avenue for in-depth study of genes involved in the regulation of physiological and developmental processes in this fungal model