Search

Hereditary hemorrhagic telangiectasia (HHT) type 2 is an autosomal dominant disease in which one allele of the ACVRL1 gene is mutated. Patients exhibit disturbances in TGF-beta/BMP-dependent angiogenesis and, clinically, often present with severe nosebleeds as well as a reduced quality of life. The aim of our study was to use CRISPR/Cas9 to knockout ACVRL1 in normal induced pluripotent stem cells (iPSCs) and evaluate the effects on TGF-beta- and BMP-related gene expression as well as angiogenesis. The CRISPR/Cas9 knockout of the ACVRL1 gene was carried out in previously characterized wild-type (ACVRL1wt/wt) iPSCs. An HHT type 2 iPS cell line was generated via a single-allele knockout (ACVRL1wt/mut) in wild-type (ACVRL1wt/wt) iPSCs, resulting in a heterozygous 17 bp frameshift deletion in the ACVRL1 gene [NG_009549.1:g.13707_13723del; NM_000020.3:c.1137_1153del]. After the generation of embryoid bodies (EBs), endothelial differentiation was induced via adding 4 ng/mL BMP4, 2% B27, and 10 ng/mL VEGF. Endothelial differentiation was monitored via immunocytochemistry. An analysis of 151 TGF-beta/BMP-related genes was performed via RT-qPCR through the use of mRNA derived from single iPS cell cultures as well as endothelial cells derived from EBs after endothelial differentiation. Differential TGF-beta/BMP gene expression was observed between ACVRL1wt/wt and ACVRL1wt/mut iPSCs as well as endothelial cells. EBs derived from CRISPR/Cas9-designed ACVRL1 mutant HHT type 2 iPSCs, together with their isogenic wild-type iPSC counterparts, can serve as valuable resources for HHT type 2 in vitro studies.

Purpose No standardized treatment regimen exists for juvenile recurrent parotitis (JRP). The investigators hypothesized that irrigation with saline only without local anesthesia will be an effective and beneficial option. Methods Using a retrospective study design, a series of children with typical symptoms of JRP who were treated with at least one irrigation therapy were evaluated. This treatment consisted of irrigation of the affected gland with 3–10 ml saline solution without any type of anesthesia. The outcome variables were patient/parent satisfaction, frequency and duration of acute JRP episodes, and the need for antibiotics before and after irrigation therapy. Results The case series was composed of six boys aged 3.3–7.7 years who experienced one to eight sessions of irrigation therapy. The period of follow-up was 9–64 months. We observed a total resolution of symptoms in two children and an improvement in the other four. No relevant side effects were seen. Conclusion Our results suggest that irrigation therapy is a reasonable, simple, and minimally invasive treatment alternative for JRP. In contrast to sialendoscopy or sialography, there is no need for general anesthesia or radiation exposure.

Zusammenfassung Hintergrund Patienten mit hereditärer hämorrhagischer Teleangiektasie (HHT) leiden unter einer systemischen Erkrankung des Gefäßbindegewebes, bei der eine Vielzahl verschiedener Symptome auftritt. Material und Methoden Die Daten aller Patienten, die sich von April 2014 bis August 2019 im Westdeutschen Morbus-Osler-Zentrum vorstellten, wurden in einer retrospektiven Studie analysiert. Ergebnisse Bei 235 Patienten konnte die Diagnose HHT als definitiv (235/282; 83 %) und bei 26 als möglich gestellt werden (26/282; 9 %). Die mittlere diagnostische Latenz zwischen Erstsymptomen und Diagnose betrug 18 Jahre. Direkte oder indirekte Blutungszeichen wurden oft als erste Symptome der Erkrankung HHT genannt (224/241; 93 %). 83 % der Patienten mit einem Grad der Behinderung gaben HHT als Hauptursache an. Insbesondere ältere, weibliche Patienten bzw. Patienten mit starker Epistaxis litten an einer chronischen Eisenmangelanämie (Eisensubstitution:148/261; 57 %; Erythrozytenkonzentrate: Mittelwert: 9 ± Standardabweichung: 41, Minimum – Maximum: 0–400, Anzahl der Patienten: 218). 10 % erhielten eine Thrombozytenaggregationshemmung oder Antikoagulation und tolerierten diese. 74 % der Patienten mit HHT pflegten ihre Nasenschleimhaut (177/238) und zeigten weniger Blutungen als Patienten ohne Nasenpflege (ESS: t-Test: 3,193; p = 0,003; Anämie: Chi-Quadrat: 5,173; p = 0,023). Schlussfolgerungen Die Diagnoselatenz der Erkrankung HHT betrug knapp 2 Jahrzehnte. Patienten mit HHT leiden insbesondere an rezidivierenden Blutungen, die dabei meistindizierte Behandlung der ersten Wahl ist eine konsequente Nasenpflege und verschiedene koagulative Therapieoptionen. Bei Begleiterkrankungen mit Indikation zur Gerinnungshemmung lohnt es sich meist, deren Einsatz zu versuchen.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved.RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Background The histological differentiation of individual types of vascular anomalies (VA), such as lymphatic malformations (LM), hemangioma (Hem), paraganglioma (PG), venous malformations (VeM), arteriovenous malformations (AVM), pyogenic granulomas (GP), and (not otherwise classified) vascular malformations (VM n.o.c.) is frequently difficult due to the heterogeneity of these anomalies. The aim of the study was to evaluate digital image analysis as a method for VA stratification Methods A total of 40 VA tissues were examined immunohistologically using a selection of five vascular endothelial-associated markers (CD31, CD34, CLDN5, PDPN, VIM). The staining results were documented microscopically followed by digital image analyses based quantification of the candidate-marker-proteins using the open source program ImageJ/Fiji. Results Differences in the expression patterns of the candidate proteins could be detected particularly when deploying the quotient of the quantified immunohistochemical signal values. Deploying signal marker quotients, LM could be fully distinguished from all other tested tissue types. GP achieved stratification from LM, Hem, VM, PG and AVM tissues, whereas Hem, PG, VM and AVM exhibited significantly different signal marker quotients compared with LM and GP tissues. Conclusion Although stratification of different VA from each other was only achieved in part with the markers used, the results of this study strongly support the usefulness of digital image analysis for the stratification of VA. Against the background of upcoming new diagnostic techniques involving artificial intelligence and deep (machine) learning, our data serve as a paradigm of how digital evaluation methods can be deployed to support diagnostic decision making in the field of VAs.

Neutron-rich 119Pd nuclei were produced in fission of natural uranium, induced by 25-MeV protons. Fission fragments swiftly extracted with the Ion Guide Isotope Separation On-Line method were mass separated using a dipole magnet and a Penning trap, providing mono-isotopic samples of 119Pd. Their β− decay was measured with γγ- and βγ-spectroscopy methods using low-energy germanium detectors and a thin plastic scintillator. Two distinct nuclear-level structures were observed in 119Ag, based on the 1/2− and 7/2+ isomers reported previously. The β−-decay work was complemented by a prompt-γ study of levels in 119Ag populated in spontaneous fission of 252Cf, performed using the Gammasphere array of germanium detectors. Contrary to previous suggestions, our data show that the 1/2− isomer is located below the 7/2+ isomer and is proposed as a new ground state of 119Ag with the 7/2+ isomer excitation energy determined to be 33.4 keV. Our data indicate that there are two β unstable isomers in 119Pd, a proposed ground state of 119Pd with tentative spin 1/2+ or 3/2+ and a half-life of 0.88 s and the other one about 350 keV above, having spin (11/2−) and a half-life of 0.85 s. The higher-energy isomer probably decays to the 1/2+ or 3/2+ ground state via a γ cascade comprising 18.7-219.8-X-keV transitions. The unobserved isomeric transition with energy X≈100 keV probably has an E3 multipolarity. Its hindrance factor is significantly lower than for analogous E3 isomeric transitions in lighter Pd isotopes, suggesting an oblate deformation of levels in 119Pd. Oblate configurations in 119Ag are discussed also. peerReviewed

International audience; Background: Nuclear structure of the neutron-rich isotopes beyond 132 Sn is investigated. Purpose: The level scheme of 137 I is obtained after decay of 137 Te. Transitions in 136 I are detected after delayed neutron emission of 137 Te. The half life of 137 Te is measured. Methods:-delayed-ray spectroscopy is employed for neutron-rich 137 Sb and 137 Te isotopes, produced at the ILL after neutron-induced fission to populate excited states in 137 I. Results: The new decay level scheme of 137 I is established. The half lives of 137 Sb and 137 Te are determined as 0.57(26) s and 2.46(5) s, respectively. The-delayed neutron emission probability P limiting value of 137 Te is deduced to be 2.17(66)%. Conclusions: The experimental results are an important input to the theoretical description of nuclei in the region, being well interpreted within LSSM calculations and provide essential information on the firstforbidden transitions beyond > 82 and > 50.

Low-spin, excited states of the 89Br nucleus, populated in β− decay of 89Se have been studied for the first time. The 89Se nuclei were produced in proton-induced fission of natural thorium using the IGISOL facility and separated using a dipole magnet and the coupled JYFLTRAP Penning trap. Gamma radiation following the β− decay of 89Se was measured with an array of high-resolution germanium detectors. Levels scheme of 89Br was extended by 12 new levels and 31 new γ transitions. Spin-parity (3/2+) has been proposed for the ground state of the 89Se mother nucleus, replacing the (5/2+) assignment reported in data bases. The observed Gamow-Teller β− transition to the 1754.5-keV level indicates a πg9/2-based configuration. The level scheme of 89Br has been compared to large scale shell-model calculations. Excitations based on πp3/2 and πf5/2 single-particle levels as well as their anomalous coupling are proposed to explain the low-energy excitation scheme of 89Br. peerReviewed