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y caregiver education or development of devices.Epigenetic regulation of transcription is a collective term that refers to mechanisms known to regulate gene transcription without changing the underlying DNA sequence. These mechanisms include DNA methylation and histone tail modifications which influence chromatin accessibility, and microRNAs that act through post-transcriptional gene silencing. Epigenetics is known to regulate a variety of biological processes, and the role of epigtenetics in immunity and immune-mediated diseases is becoming increasingly recognized. While DNA methylation is the most widely studied, each of these systems play an important role in the development and maintenance of appropriate immune responses. There is clear evidence that epigenetic mechanisms contribute to developmental stage-specific immune responses in a cell-specific manner. There is also mounting evidence that prenatal exposures alter epigenetic profiles and subsequent immune function in exposed offspring. Early life exposures that are associated with poor long-term health outcomes also appear to impact immune specific epigenetic patterning. Finally, each of these epigenetic mechanisms contribute to the pathogenesis of a wide variety of diseases that manifest during childhood. This review will discuss each of these areas in detail. IMPACT Epigenetics, including DNA methylation, histone tail modifications, and microRNA expression, dictate immune cell phenotypes. Epigenetics influence immune development and subsequent immune health. Prenatal, perinatal, and postnatal exposures alter immune cell epigenetic profiles and subsequent immune function. Numerous pediatric-onset diseases have an epigenetic component. Several successful strategies for childhood diseases target epigenetic mechanisms.<br />Malnutrition (MN) in nursing home (NH) residents is associated with poor outcome. In order to identify those with a high risk of incident MN, the knowledge of predictors is crucial. Therefore, we investigated predictors of incident MN in older NH-residents.<br />NH-residents participating in the nutritionDay-project (nD) between 2007 and 2018, aged ≥65 years, with complete data on nutritional status at nD and after 6 months and without MN at nD. The association of 17 variables (general characteristics (n = 3), function (n = 4), nutrition (n = 1), diseases (n = 5) and medication (n = 4)) with incident MN (weight loss ≥ 10% between nD and follow-up (FU) or BMI (kg/m<br />) &lt; 20 at FU) was analyzed in univariate generalized estimated equation (GEE) models. Significant (p &lt; 0.1) variables were selected for multivariate GEE-analyses. Effect estimates are presented as odds ratios and their respective 99.5%-confidence intervals.<br />Of 11,923 non-malnourished residents, 10.5% developed MN at FU. No intake at lunch (OR 2.79 [1.56-4.98]), a quarter (2.15 [1.56-2.97]) or half of the meal eaten (1.72 [1.40-2.11]) (vs. three-quarter to complete intake), the lowest BMI-quartile (20.0-23.0) (1.86 [1.44-2.40]) (vs. highest (≥29.1)), being between the ages of 85 and 94 years (1.46 [1.05; 2.03]) (vs. the youngest age-group 65-74 years)), severe cognitive impairment (1.38 [1.04; 1.84]) (vs. none) and being immobile (1.28 [1.00-1.62]) (vs. mobile) predicted incident MN in the final model.<br />10.5% of non-malnourished NH-residents develop MN within 6 months. Attention should be paid to high-risk groups, namely residents with poor meal intake, low BMI, severe cognitive impairment, immobility, and older age.<br />10.5% of non-malnourished NH-residents develop MN within 6 months. Attention should be paid to high-risk groups, namely residents with poor meal intake, low BMI, severe cognitive impairment, immobility, and older age.Patients with Coronavirus disease 2019 exhibit low expression of interferon-stimulated genes, contributing to a limited antiviral response. Uncovering the underlying mechanism of innate immune suppression and rescuing the innate antiviral response remain urgent issues in the current pandemic. Here we identified that the dimerization domain of the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is required for SARS2-NP to undergo liquid-liquid phase separation with RNA, which inhibits Lys63-linked poly-ubiquitination and aggregation of MAVS and thereby suppresses the innate antiviral immune response. Mice infected with an RNA virus carrying SARS2-NP exhibited reduced innate immunity, an increased viral load and high morbidity. Notably, we identified SARS2-NP acetylation at Lys375 by host acetyltransferase and reported frequently occurring acetylation-mimicking mutations of Lys375, all of which impaired SARS2-NP liquid-liquid phase separation with RNA. Importantly, a peptide targeting the dimerization domain was screened out to disrupt the SARS2-NP liquid-liquid phase separation and demonstrated to inhibit SARS-CoV-2 replication and rescue innate antiviral immunity both in vitro and in vivo.Inflammatory bowel diseases present with elevated levels of intestinal epithelial cell (IEC) death, which compromises the gut barrier, activating immune cells and triggering more IEC death. The endogenous signals that prevent IEC death and break this vicious cycle, allowing resolution of intestinal inflammation, remain largely unknown. Here we show that prostaglandin E2 signalling via the E-type prostanoid receptor 4 (EP4) on IECs represses epithelial necroptosis and induces resolution of colitis. We found that EP4 expression correlates with an improved IBD outcome and that EP4 activation induces a transcriptional signature consistent with resolution of intestinal inflammation. We further show that dysregulated necroptosis prevents resolution, and EP4 agonism suppresses necroptosis in human and mouse IECs. Mechanistically, EP4 signalling on IECs converges on receptor-interacting protein kinase 1 to suppress tumour necrosis factor-induced activation and membrane translocation of the necroptosis effector mixed-lineage kinase domain-like pseudokinase. In summary, our study indicates that EP4 promotes the resolution of colitis by suppressing IEC necroptosis.Tissue turnover requires activation and lineage commitment of tissue-resident stem cells (SCs). These processes are impacted by ageing, but the mechanisms remain unclear. Here, we addressed the mechanisms of ageing in murine hair follicle SCs (HFSCs) and observed a widespread reduction in chromatin accessibility in aged HFSCs, particularly at key self-renewal and differentiation genes, characterized by bivalent promoters occupied by active and repressive chromatin marks. Consistent with this, aged HFSCs showed reduced ability to activate bivalent genes for efficient self-renewal and differentiation. These defects were niche dependent as the transplantation of aged HFSCs into young recipients or synthetic niches restored SC functions. Mechanistically, the aged HFSC niche displayed widespread alterations in extracellular matrix composition and mechanics, resulting in mechanical stress and concomitant transcriptional repression to silence promoters. As a consequence, increasing basement membrane stiffness recapitulated age-related SC changes. These data identify niche mechanics as a central regulator of chromatin state, which, when altered, leads to age-dependent SC exhaustion.Aim To determine if a single pre-operative dose of oral corticosteroids would be effective in reducing pain, trismus and oedema following lower third molar surgical extraction. Secondary outcomes of interest were post-operative complications such as infections.Methods Searching was conducted using Embase, Medline, DOSS, CINAHL and CENTRAL for randomised controlled trials. Four studies which compared pre-operative oral corticosteroids to placebo before lower third molar surgical extractions were eligible for inclusion.Results All studies were judged to be at unclear risk of bias. All studies tested the efficacy of 8 mg dexamethasone 60-90 minutes before surgical extractions. While three studies showed improvement in pain visual analogue scale (VAS) scores in the dexamethasone groups, two were not statistically significant. One study found no improvement in pain scores on VAS. One study found no difference in either trismus or oedema. One study reported one occurrence of post-operative alveolar infection in the dexamethasone group and one occurrence of alveolar osteitis in the placebo group.Conclusion While there seems to be an improvement in pain scores on VAS, these results are not clinically significant. Post-operative analgesia plays a more important role clinically.Introduction Nursing home residents with cognitive and physical disabilities often depend on assistance from caregivers to perform personal hygiene tasks including toothbrushing. Only a minority receives the care needed and toothbrushing compliance levels are not registered.Aims To describe toothbrushing compliance levels in a nursing home setting and investigate the relevance and practicality of using telemonitoring-enabled powered toothbrushes for automated compliance tracking. [https://www.selleckchem.com/products/cc-930.html Tanzisertib in vivo] Furthermore, to investigate changes in plaque and bleeding scores.Materials and methods Nursing home residents were provided with powered toothbrushes and telemonitoring gateways. Toothbrushing frequency and duration were automatically recorded by the telemonitoring gateways, and an email report was sent once a week to the nursing home manager. Plaque index and bleeding index were assessed by dentists at baseline, at the end of the intervention and at three months post-intervention.Results Data from 20 participants for 100 days (3,920 measurements) were collected and used to evaluate toothbrushing compliance. A minority of toothbrushings (5%) were in compliance with the two-minute toothbrushing duration recommendation, while around 30% achieved the one-minute toothbrushing minimum duration recommendation. Around 25% of participants would get only one toothbrushing per day, while 40% would get none. Both plaque and bleeding scores improved significantly during the project, but all progress was lost three months after the project's end.Conclusions It is relevant and practical to monitor toothbrushing compliance in the nursing home setting using telemonitoring-enabled powered toothbrushes. Despite finding limited compliance levels, a significant improvement in the plaque and bleeding index was found after the intervention, which was lost again three months after the telemonitoring gateways had been removed.Aim To investigate the relationship between generic and condition-specific (CS) quality of life, general psychological wellbeing and personality in patients with tooth wear.Materials and methods Ethical approval was granted (REC10/H0709/21). Patients aged 18-70 years with tooth wear completed the Oral Impact on Daily Performance (OIDP) quality of life questionnaire, the NEO-FFI Personality questionnaire and the General Health Questionnaire-12 (GHQ). Tooth wear was measured with the Basic Erosive Wear Examination (BEWE).Results In total, 102 subjects were recruited. Increased BEWE scores were correlated with older age and worse generic and CS-related quality of life. Increased neuroticism was correlated with increased generic and CS OIDP scores; generic and CS eating scores; CS smiling scores; and CS carrying out major work scores. Increased GHQ scores were positively correlated with increased generic and CS OIDP scores; generic and CS eating scores; CS speaking scores; generic and CS cleaning scores; generic relaxing scores; generic and CS smiling scores; and generic emotional state scores (p less then 0.