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Dimension to enhance Treatment Shipping: A new Remarks around the HiTOP Measure Improvement Undertaking.
6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies. © 2020 John Wiley & Sons Ltd.Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation of such genes is often accompanied by repositioning toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are poorly understood. We addressed these questions by systematic activation or inactivation of individual genes, followed by detailed genome-wide analysis of NL interactions, replication timing, and transcription patterns. Gene activation inside LADs typically causes NL detachment of the entire transcription unit, but rarely more than 50-100 kb of flanking DNA, even when multiple neighboring genes are activated. The degree of detachment depends on the expression level and the length of the activated gene. Loss of NL interactions coincides with a switch from late to early replication timing, but the latter can involve longer stretches of DNA. Inactivation of active genes can lead to increased NL contacts. These extensive datasets are a resource for the analysis of LAD rewiring by transcription and reveal a remarkable flexibility of interphase chromosomes. © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMCHD1) has been implicated in X-chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumeral muscular dystrophy. More recently, SMCHD1 has also been identified as a component of telomeric chromatin. Here, we report that SMCHD1 is required for DNA damage signaling and non-homologous end joining (NHEJ) at unprotected telomeres. Co-depletion of SMCHD1 and the shelterin subunit TRF2 reduced telomeric 3'-overhang removal in time-course experiments, as well as the number of chromosome end fusions. SMCHD1-deficient cells displayed reduced ATM S1981 phosphorylation and diminished formation of γH2AX foci and of 53BP1-containing telomere dysfunction-induced foci (TIFs), indicating defects in DNA damage checkpoint signaling. Removal of TPP1 and subsequent activation of ATR signaling rescued telomere fusion events in TRF2-depleted SMCHD1 knockout cells. Together, these data indicate that SMCHD1 depletion reduces telomere fusions in TRF2-depleted cells due to defects in ATM-dependent checkpoint signaling and that SMCHD1 mediates DNA damage response activation upstream of ATM phosphorylation at uncapped telomeres. © 2020 The Authors.BACKGROUND The diagnosis and management of patients suffering from occlusal dysesthesia (OD) remain a major challenge for dental practitioners and affected patients. OBJECTIVES To present the results of a literature-based expert consensus intended to promote better understanding of OD and to facilitate the identification and management of affected patients. METHODS In 2018, electronic literature searches were carried out in PubMed, Cochrane Library and Google Scholar as well as in the archives of relevant journals not listed in these databases. This approach was complemented by a careful assessment of the reference lists of the identified relevant papers. The articles were weighted by evidence level, followed by an evaluation of their contents and a discussion. The result represents an expert consensus. RESULTS Based on the contents of the 77 articles identified in the search, the current knowledge about clinical characteristics, epidemiology, aetiology, diagnostic process, differential diagnosis and management of OD is summarised. CONCLUSIONS Occlusal dysesthesia exists independently of the occlusion. Instead, it is the result of maladaptive signal processing. this website The focus should be on patient education, counselling, defocusing, cognitive behavioural therapy, supportive drug therapy and certain non-specific measures. Irreversible, specifically an exclusively dental treatment approach must be avoided. © 2020 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.Oral motor exercises, for recovering tongue strength, can be integrated with computer games to increase motivation, especially for treatments in children. The aim of this study was to investigate the influence of tongue strength on motor performance in computer games reliant on lingual force generation. An observational study was carried out at a speech-language pathology outpatient university clinic. Twenty participants (10 with normal tongue strength and 10 with reduced tongue strength) aged 8-13 years used an intra-oral joystick controlled by the tongue to play six computer games during which they had to reach targets that appeared on the screen. Motor performance was measured by the number of attempts to score and the time during which the target force was maintained. Tongue motor performance was compared between groups and across directions of tongue movement, resistance force levels, order of target appearance, continuous force application time on the target, age and sex. Children with normal tongue strength had a lower number of attempts to score (P = .014) and maintained the target force for longer periods (P = .002) than those with reduced tongue strength. The performance was better for both groups (a) in the downward direction compared with the performance in other directions, (b) in games with the lowest resistive force level (0.5 N) compared to those with other levels of resistive force and (c) in the second and third rounds compared with the first round. There were no gender-related differences in performance. Older participants performed better than younger participants. Tongue strength, direction of movement, force to reach the target, time of continuous force application, order of target appearance and age influenced tongue motor performance. © 2020 John Wiley & Sons Ltd.
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