Portal Embolisation as Treatment of Severe Portal Hypertension Due to Idiopathic Intrahepatic Arterioportal Fistula:A Case Report

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Treatment is usually aimed at restoring the normal portal hemodynamics by obliterating the shunt. This report describes a case of idiopathic IAPF with severe portal hypertension complicated by portal enteropathy with vomiting, gastrointestinal hemorrhage and sepsis. The patient was successfully treated with portal embolization.</p

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment

Direct and indirect methods for the quantification of leg volume: Comparison between water displacement volumetry, the disk model method and the frustum sign model method, using the correlation coefficient and the limits of agreement

Volume changes can be measured either directly by water-displacement volumetry or by various indirect methods in which calculation of the volume is based on circumference measurements. The aim of the present study was to determine the most appropriate indirect method for lower leg volume calculation using water displacement volumetry as a ‘golden standard’. For 20 male volunteers, age range: 20–35 years, the volume of both lower legs was determined directly by water-displacement volumetry, and indirectly by the frustum sign model method and the disc model method. Calculation of the correlation coefficient and the limits of agreement showed that water-displacement volumetry and the disc model method are interchangeable (r = + 0.99, mean ± 2s = − 45 ± 78 ml), whereas this does not hold for the frustum sign model (r = + 0.93, mean ± 2s = 521 ± 238 ml). In the clinical situation volume measurement can be valuable for monitoring of the severity of oedema or haematoma occurrence after surgery or severe trauma. This non-invasive diagnostic aid may be a valuable adjuvant means of diagnosis for several volume dependent disorders of the extremities

Characterisation of the TBR1 interactome: variants associated with neurodevelopmental disorders disrupt novel protein interactions

TBR1 is a neuron-specific transcription factor involved in brain development and implicated in a neurodevelopmental disorder (NDD) combining features of autism spectrum disorder (ASD), intellectual disability (ID) and speech delay. TBR1 has been previously shown to interact with a small number of transcription factors and co-factors also involved in NDDs (including CASK, FOXP1/2/4 and BCL11A), suggesting that the wider TBR1 interactome may have a significant bearing on normal and abnormal brain development. Here we have identified approximately 250 putative TBR1-interaction partners by affinity purification coupled to mass spectrometry. As well as known TBR1-interactors such as CASK, the identified partners include transcription factors and chromatin modifiers, along with ASD- and ID-related proteins. Five interaction candidates were independently validated using bioluminescence resonance energy transfer assays. We went on to test the interaction of these candidates with TBR1 protein variants implicated in cases of NDD. The assays uncovered disturbed interactions for NDD-associated variants and identified two distinct protein-binding domains of TBR1 that have essential roles in protein–protein interaction

On subsequential spaces

AbstractSimple generators for the coreflective category of subsequential spaces, one of them countable, are constructed. Every such must have subsequential order ω1. Subsequentialness is a local property and a countable property, both in a strong sense. A T2-subsequential space may be pseudocompact without being sequential, in contrast to T2-subsequential compact (countably compact, sequentially compact) spaces all being sequential. A compact subsequential space need not be sequential

Induced pluripotent stem cells from subjects with Lesch-Nyhan disease

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Gene expression profiling with RNAseq demonstrated significant heterogeneity among the lines. Despite this heterogeneity, several anticipated abnormalities were readily detectable across all LND lines, including reduced HPRT1 mRNA. Several unexpected abnormalities were also consistently detectable across the LND lines, including decreases in FAR2P1 and increases in RNF39. Shotgun proteomics also demonstrated several expected abnormalities in the LND lines, such as absence of HGprt protein. The proteomics study also revealed several unexpected abnormalities across the LND lines, including increases in GNAO1 decreases in NSE4A. There was a good but partial correlation between abnormalities revealed by the RNAseq and proteomics methods. Finally, functional studies demonstrated LND lines had no HGprt enzyme activity and resistance to the toxic pro-drug 6-thioguanine. Intracellular purines in the LND lines were normal, but they did not recycle hypoxanthine. These cells provide a novel resource to reveal insights into the relevance of heterogeneity among iPSC lines and applications for modeling LND

Helicobacter pylori colonization and obesity - A Mendelian randomization study

Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n = 13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p = 0.03) and with obesity classes (Beta -6.91 •10-5; 95% CI -1.38•10-4, -5.49•10-7, p = 0.048), but the magnitude of these effects was limited. Mendelian randomization showed no causal relation between H. pylori genetic risk score and BMI/obesity, nor between BMI or obesity genetic risk scores and H. pylori positivity. This study provides no evidence for a clinically relevant association between H. pylori and BMI/obesity

Development and clinical evaluation of a 3-step modified manipulation protocol for MRI-guided high-intensity focused ultrasound of uterine fibroids

__Objectives:__ The clinical applicability of magnetic resonance image−guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids is often limited due to inaccessible fibroids or bowel interference. The aim of this study was to implement a newly developed 3-step modified manipulation protocol and to evaluate its influence on the number of eligible women and treatment fai

An Isolator System for minimally invasive surgery: the new design

Background - The risk of obtaining a postsurgical infection depends highly on the air quality surrounding the exposed tissue, surgical instruments, and materials. Many isolators for open surgery have been invented to create a contained sterile volume around the exposed tissue. With the use of an isolator, a surgical procedure can be performed outside sterile environments. The goal of this study was to design an Isolator System (IS) for standard laparoscopic instruments while instrument movements are not restricted. Methods - The developed IS consists of a sleeve to protect the instrument shaft and tip and a special balloon to protect the incision and trocar tube. A coupling mechanism connected at the sleeve allows instrument changes without contamination of the isolated parts. Smoke tests were performed to show that outside air does not enter the new IS during a simulated laparoscopic procedure. Eight test runs and one baseline run inside a contained volume filled with thick smoke were performed to investigate whether smoke particles entered the Isolator System. Filters were used to identify smoke entering the Isolator System. Results - Seven filters showed no trace of smoke particles. In one test run, a part of the IS loosened and a small brown spot was visible. The filter from the baseline run was completely covered with a thick layer of particles, proving the effectiveness of the test. During all test runs, the isolated instrument was successfully locked on and unlocked from the isolated trocar. Instrument movements gave no complications. After removal of the isolated instrument, it took three novices an average of 3.1 (standard deviation (SD), 0.7) seconds to replace it correctly on the isolated trocar. Conclusions - The designed IS for laparoscopy can increase sterility in environments where sterility cannot be guaranteed. The current design is developed for laparoscopy, but it can easily be adapted for other fields in minimally invasive surgery.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin