Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.Funding for the project was provided by the Wellcome Trust for UK10K (WT091310) and DDD Study. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003] - see www.ddduk.org/access.html for full acknowledgement. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Common Fund, NIH Office of the Director. This work was supported in part by the German Ministry of Research and Education (grant nos. 01GS08160 and 01GS08167; German Mental Retardation Network) as part of the National Genome Research Network to A.R. and D.W. and by the Deutsche Forschungsgemeinschaft (AB393/2-2) to A.R. Brain expression data was provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Michael Weale, Daniah Trabzuni, Adaikalavan Ramasamy, Colin Smith and Robert Walker, affiliated with UCL Institute of Neurology (J.H., M.R., D.T.), King’s College London (M.R., M.W., A.R.) and the University of Edinburgh (C.S., R.W.)

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

8th European Conference on Rare Diseases & Orphan Products (ECRD 2016)

MEETING ABSTRACTS: Open Access 8th European Conference on Rare Diseases & Orphan Products (ECRD 2016), Edinburgh, UK. 26-28 May 201

Linked open hotel

The evolution of the Web has enabled various stakeholders to reach new audiences and offer their services via new distribution channels and media. It is a fact that online purchases of touristic products (e.g. hotel reservations, flight tickets) have increased exponentially in the last few years. Furthermore, the recent achievements in the scope of the Web 3.0 paradigm have triggered the attention of the different businesses. Annotating semantically online content is a key enabler for promising applications of the semantic web technologies. The current study describes and demonstrates a useful approach of application of the state of the art Web technologies to annotate the content of accommodation websites. The proposed best practices could enable the lodging businesses to improve the visibility of their services and empower their marketing strategies.presented by Laimer DanielAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersUniversität Innsbruck, Masterarbeit, 2018(VLID)244862

Linked open hotel

The evolution of the Web has enabled various stakeholders to reach new audiences and offer their services via new distribution channels and media. It is a fact that online purchases of touristic products (e.g. hotel reservations, flight tickets) have increased exponentially in the last few years. Furthermore, the recent achievements in the scope of the Web 3.0 paradigm have triggered the attention of the different businesses. Annotating semantically online content is a key enabler for promising applications of the semantic web technologies. The current study describes and demonstrates a useful approach of application of the state of the art Web technologies to annotate the content of accommodation websites. The proposed best practices could enable the lodging businesses to improve the visibility of their services and empower their marketing strategies.presented by Laimer DanielAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersUniversität Innsbruck, Masterarbeit, 2018(VLID)244862

Can accurate evaluation of the treatment success after radiofrequency ablation of liver tumors be achieved by visual inspection alone? Results of a blinded assessment with 38 interventional oncologists

Objectives To assess the difficulties in the immediate judgment of treatment success after radiofrequency ablation (RFA) of liver tumors by visual inspection alone and to evaluate whether radiologist’s expertise affects the resultant judgment. Methods Peri-interventional CT-scans of nine patients with nine hepatocellular carcinomas with known outcomes after RFA were presented to 38 participants from 14 different countries. In a total of 342 reads, all interventional oncologists assessed the pre- and immediate post-interventional CT-scans through conventional side-by-side juxtapositioning of images and judged whether complete ablation (i.e., technical success and technique efficacy) was achieved. Results were compared regarding expertise in percutaneous tumor ablation (>50 interventions performed). An ‘overcall’ was defined as insufficient ablation that was misjudged as sufficient, and an ‘undercall’ as an erroneous assessment of complete ablation. Results Overall 3.97 ± 1.27 out of 9 (44.1%) cases per radiologist were misjudged. The mean number of overcalls and undercalls per radiologist were 0.74 ± 0.50 out of 2 (37.0%), and 3.24 ± 1.28 out of 7 (46.3%), respectively. 18/38 (47.4%) participants had considerable experience in percutaneous tumor ablation, with such expertise having no significant influence on the results (overall: p = 0.70; overcalls: p = 0.87; undercalls: p = 0.75). Conclusions Conventional side-by-side evaluation of treatment success after RFA of liver tumors by the juxtaposition of pre- and post-interventional CT-scans is very difficult for experienced radiologists. The implementation of advanced processing techniques such as rigid/non-rigid image fusion with the assessment of the periablational margin is thus likely needed in order to decrease errors and objectively evaluate technical success and predict technique efficacy of liver RFA

Wernicke Encephalopathy: a Future Problem Even After Sleeve Gastrectomy? A Systematic Literature Review.

Wernicke encephalopathy (WE) is a serious complication of bariatric surgery with significant morbidity and mortality. A few cases have been reported in the literature, mainly in patients after a Roux-en-Y gastric bypass. Since sleeve gastrectomy (SG) has become a more established and popular bariatric procedure, WE is expected to appear more frequently after SG. We performed a literature review on WE after SG, and 13 cases have been found to be sufficiently documented. The risk of WE needs to be considered in patients with a prolonged vomiting episode and any type of neurological symptoms, independent of the presence of any surgical complications

Reliability of Stereotactic Radiofrequency Ablation (SRFA) for Malignant Liver Tumors: Novice versus Experienced Operators

Purpose: To compare the results of a novice with those of experienced interventional radiologists (IRs) for stereotactic radiofrequency ablation (SRFA) of malignant liver tumors in terms of safety, technical success, and local tumor control. Methods: A database, including all SRFA procedures performed in a single center between January 2011 and December 2018 was retrospectively analyzed. A total of 39 ablation sessions performed by a novice IR were compared to the results of three more experienced IRs. Comparative SRFA sessions were selected using propensity score matching considering tumor type, age, sex, tumor size, and tumor number as matching variables. Overall, 549 target tumors were treated in 273 sessions. Median tumor size was 2.2 cm (1.0–8.5 cm) for 178 hepatocellular carcinomas (HCCs) and 3.0 cm (0.5–13.0 cm) for 371 metastases. A median of 2 (1–11) tumors were treated per session. Results: No significant differences were observed when comparing the results of more experienced IRs with those of a novice IR regarding the rates of major complications (6.8% [16/234] vs. 5.1% [2/39]; p = 0.477), mortality (1.3% [2/234] vs. 0% [0/39]; p = 0.690), primary technical efficacy (98.5% [525/533] vs. 98.9% [94/95]; p = 0.735), and local recurrence (5.6% [30/533] vs. 5.3% [5/95]; p = 0.886). However, the median planning/placement time was significantly shorter for the experienced IRs (92 min vs. 119 min; p = 0.002). Conclusions: SRFA is a safe, effective, and reliable treatment option for malignant liver tumors and favorable outcomes can be achieved even by inexperienced operators with minimal supervision