DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway

The DNA damage response (DDR), comprising distinct repair and signalling pathways, safeguards genomic integrity. Protein ubiquitylation is an important regulatory mechanism of the DDR. To study its role in the UV-induced DDR, we characterized changes in protein ubiquitylation following DNA damage using quantitative di-Gly proteomics. Interestingly, we identified multiple sites of histone H1 that are ubiquitylated upon UV-damage. We show that UV-dependent histone H1 ubiquitylation at multiple lysines is mediated by the E3-ligase HUWE1. Recently, it was shown that poly-ubiquitylated histone H1 is an important signalling intermediate in the double strand break response. This poly-ubiquitylation is dependent on RNF8 and Ubc13 which extend pre-existi

Health-related quality-of-life measures for long-term follow-up in children after major trauma

Objective: Our objective was to review measures of health-related quality of life (HRQL) for long-term follow up in children after major trauma and to determine the measures that are suitable for a large age range, reliable and valid, and cover a substantial amount of the domains of functioning using the International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization (WHO). Methods: The Medline and EMBASE databases were searched in all years up to October 2007 for generic HRQL measures suitable for children aged 5-18 years old and validated in English or Dutch. Measures were reviewed with respect to the age range for which the measure was suitable and reliability, validity, and content related to the ICF. Results: The search resulted in 1,235 hits and 21 related articles. Seventy-nine papers met the inclusion criteria, describing in total 14 measures: Child Health and Illness Profile Adolescent and Child Edition (CHIP-AE/CE), Child Health Questionnaire Child and Parent Forms (CHQCF87/PF50/PF28), DISABKIDS, Functional Status II (FS II)(R), Health Utilities Index Mark 2 (HUI 2), KIDSCREEN 52/27, KINDL, Pediatric Quality of Life Inventory (PedsQL), TNO Institute of Prevention and Health and the Leiden University Hospital (TNO-AZL), TNO-AZL Children’s Quality Of Life (TACQOL), and Youth Quality of Life Instrument-Research Version (YQOL-R). Measures that were suitable for a large age range were CHQ-PF50/PF28, DISABKIDS, FS II(R), HUI 2, KIDSCREEN, PedsQL, and TACQOL. All measures had moderate to good psychometric properties, except for CHQ-PF50/PF28, KINDL, and TACQOL, which had either low internal consistency or bad test-retest reliability. The measures that covered more than six chapters of the ICF domains were CHIP-AE/CE, CHQ-CF87/PF50, DISABKIDS, KIDSCREEN-52, PedsQL, and TACQOL. Conclusions: DISABKIDS, KIDSCREEN 52, and Peds-QL are suitable for long-term follow-up measurement of HRQL in children after major trauma. They cover a large age range, have good psychometric properties, and cover the ICF substantially

Rationale and design of a prospective substudy of clinical endpoint adjudication processes within an investigator-reported randomised controlled trial in patients with coronary artery disease: the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY)

pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias. Methods and analysis We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, nonfatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria. This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events. Ethics and dissemination GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not neces

Degloved foot sole successfully reconstructed with split thickness skin grafts

Introduction The current opinion is that split thickness skin grafts are not suitable to reconstruct a degloved foot sole. The tissue is too fragile to carry full bodyweight; and therefore, stress lesions frequently occur. The treatment of choice is the reuse of the avulsed skin whenever possible, or else the use of a full thickness fascio-cutaneus flap. Presentation of the case A young male sustained a crush injury to his right foot with deglovement of the plantar surface and part of the dorsum. Discussion Split thickness skin grafts are not suitable for full weight bearing, but in special circumstances, certain patients, a lot of time and patience, early mobilization and gradual increasing partial weight bearing it is worthwhile to try. To toughen the foot sole pressure distribution is necessary and can be reached in several ways, soft and springy materials of the inlay, but also socks, orthopedic shoes, casting, orthotics or walking aids. Conclusion This case-report illustrates that the reconstruction of a degloved foot sole with split-thickness skin grafts can be successful; a silicon inner sole was used to prevent stress lesions

Big humidity data from smart ventilation systems

A smart ventilation system is generally equipped with a range of sensors. The data – or data derived from it - collected by these sensors can be used by both building owners, occupants and managers. A new generation of IoT enabled residential ventilation systems allows collecting and analysing this data at scale to get a better view on typical IAQ conditions in dwellings. In this paper, the results from such an analysis on the first 900 installed devices of a new model with respect to moisture in relatively new Belgian dwellings is presented

Studies on the Depth of Crown of Rice, Wheat and Barly Plant 4 : Effects of oxidation reduction potential in soil and soil humidity on the length of subcrown-internode and the depth of crown

textabstractXPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. However, the exact regulatory function of these modifications in vivo remains elusive. Here we show that RNF111 is required for efficient repair of ultraviolet-induced DNA lesions. RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation, and is needed for stable incorporation of the NER endonucleases XPG and ERCC1/XPF. Our data suggest that RNF111, together with the CRL4^DDB2 ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction, thereby providing an extra layer of quality control of NER

Prehospital Triage of Intracranial Hemorrhage and Anterior Large‐Vessel Occlusion Ischemic Stroke: Value of the Rapid Arterial Occlusion Evaluation

Background The Rapid Arterial oCclusion Evaluation (RACE) score can identify patients with anterior circulation large‐vessel occlusion (aLVO) ischemic stroke for transportation to a comprehensive stroke center for endovascular thrombectomy. However, patients with intracranial hemorrhage (ICH) may also benefit from direct transportation to a comprehensive stroke center for neurosurgical treatment. We aimed to assess if the RACE score can distinguish patients with ICH in addition to aLVO stroke from other patients with suspected stroke. Methods We analyzed data from the LPSS (Leiden Prehospital Stroke Study), a multicenter, prospective, observational cohort study in 2 Dutch ambulance regions. Ambulance paramedics documented prehospital observations in all patients aged ≥18 years with suspected stroke. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of a positive RACE score (≥5 points) for a diagnosis of ICH or aLVO stroke, compared with patients with non‐aLVO stroke, transient ischemic attack, or stroke mimic. In addition, we performed a multivariable logistic regression analysis and calculated adjusted odds ratios (ORs). Results We included 2004 patients with a stroke code, of whom 149 had an ICH, 153 had an aLVO stroke, 687 had a non‐aLVO stroke, 262 had a transient ischemic attack, and 753 had a stroke mimic. Patients with ICH and aLVO stroke more often had a positive RACE score than other patients with suspected stroke (46.2% and 58.0%, respectively, versus 6.4%; P<0.01). A positive RACE score had a sensitivity of 52.7%, a specificity of 93.6%, a positive predictive value of 55.4%, and a negative predictive value of 92.9% for a diagnosis of ICH or aLVO stroke. In multivariable analysis, a positive RACE score had the strongest association with ICH or aLVO stroke (adjusted OR, 10.11 [95% CI, 6.84–14.93]). Conclusions Our study shows that the RACE score can also identify patients with ICH in addition to aLVO stroke. This emphasizes the potential of the RACE score for improving prehospital triage and allocation of patients with stroke

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Summary: Aging increases the risk of age-related diseases, imposing substantial healthcare and personal costs. Targeting fundamental aging mechanisms pharmacologically can promote healthy aging and reduce this disease susceptibility. In this work, we employed transcriptome-based drug screening to identify compounds emulating transcriptional signatures of long-lived genetic interventions. We discovered compound 60 (Cmpd60), a selective histone deacetylase 1 and 2 (HDAC1/2) inhibitor, mimicking diverse longevity interventions. In extensive molecular, phenotypic, and bioinformatic assessments using various cell and aged mouse models, we found Cmpd60 treatment to improve age-related phenotypes in multiple organs. Cmpd60 reduces renal epithelial-mesenchymal transition and fibrosis in kidney, diminishes dementia-related gene expression in brain, and enhances cardiac contractility and relaxation for the heart. In sum, our two-week HDAC1/2 inhibitor treatment in aged mice establishes a multi-tissue, healthy aging intervention in mammals, holding promise for therapeutic translation to promote healthy aging in humans