Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1

Urothelial carcinoma (UC) is a common disease causing significant morbidity and mortality as well as considerable costs for health systems. Extensive aberrant methylation of DNA is broadly documented in early UC, contributing to genetic instability, altered gene expression and tumor progression. However the triggers initiating aberrant methylation are unknown. Recently we discovered that several genes encoding key enzymes of methyl group and polyamine metabolism, including Ornithine Decarboxylase 1 (ODC1), are affected by DNA methylation in early stage UC. In this study, we investigated the hypothesis that these epigenetic alterations act in a feed-forward fashion to promote aberrant DNA methylation in UC. We demonstrate that siRNA-mediated knockdown of ODC1 expression elicits genome-wide LINE-1 demethylation, induction of LINE-1 transcripts and double-strand DNA breaks and decreases viability in primary cultured uroepithelial cells. Similarly, following siRNA-mediated knockdown of ODC1, UC cells undergo double-strand DNA breaks and apoptosis. Collectively, our findings provide evidence that ODC1 gene hypermethylation could be a starting point for the onset of genome-wide epigenetic aberrations in urothelial carcinogenesis. Furthermore, LINE-1 induction enabled by ODC1 interference provides a new experimental model to study mechanisms and consequences of LINE-1 activation in the etiology and progression of UC as well as presumably other cancers

Management of nystagmus in children : a review of the literature and current practice in UK specialist services

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management

Managing Nystagmus in childhood

The onset of a spontaneous oscillation of the eyes can occur at any time in life but is most commonly encountered during childhood. In the UK, nystagmus in the general population has been reported to have a prevalence of 2.4 in 1000. It can occur as an isolated disorder, in association with a number of different eye conditions, or as a result of a range of neurological disorders. The onset of nystagmus in childhood is not rare and can be the cause of significant clinical and parental concern, and sometimes requires urgent investigation. There is currently no standard clinical approach to investigating nystagmus in childhood. This Clinical Practice Point provides a single point of reference for busy clinicians when managing these complex patients from differential diagnosis, through long-term management, to discharge. It also covers provision of support for patients and carers throughout and beyond clinical care pathways. This document is specific to nystagmus in children

Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study

Purpose Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers. Methods A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: “Do you, or anyone you know well, have nystagmus?”. Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods. Results One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered “Yes” to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition. Conclusion This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders. Peer Review report

Enhancer evolution across 20 mammalian species.

The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.We thank Stephen Watt, Frances Connor, the CRUK-CI Genomics and Bioinformatics cores, Biological Resources Unit (Matthew Clayton), Margaret Brown (West Yorkshire bat hospital), Julie E. Horvath (North Carolina Central University), and Chris Dillingham (University of Cardiff) for technical assistance; Matthieu Muffato for assistance with whole-genome alignments; Claudia Kutter, Gordon Brown, Christine Feig, and Christina Ernst for useful comments and discussions, and the EBI systems team for management of computational resources. This research was supported by Cancer Research UK (D.V., D.T.O.), the European Molecular Biology Laboratory (C.B., P.F.), the Wellcome Trust (WT095908) (P.F.) and (WT098051) (P.F., D.T.O.), the European Research Council, EMBO Young Investigator Programme (D.T.O.), the National Science Foundation (0744979) (T.J.P.), NIH (P40 OD010965, R01 OD010980, R37 MH060233) (A.J.J.) and MRC (U117588498) (J.M.A.T.). Cetacean samples were collected by the UK Cetacean Strandings Investigation Programme, funded by Defra and the Governments of Scotland and Wales.This is the final version. It originally appeared at http://www.sciencedirect.com/science/article/pii/S0092867415000070

Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions

Background Individuals with 22q11.2 deletion are at considerably increased risk of neurodevelopmental and psychiatric conditions. There have been very few studies investigating how this risk manifests in early childhood and what factors may underlie developmental variability. Insights into this can elucidate transdiagnostic markers of risk that may underlie later development of neuropsychiatric outcomes. Methods Thirty two children with 22q11.2 Deletion Syndrome (22q11.2DS) (mean age = 4.1 [SD = 1.2] years) and 12 sibling controls (mean age = 4.1 [SD = 1.5] years) underwent in-depth dimensional phenotyping across several developmental domains selected as being potential early indicators of neurodevelopmental and psychiatric liability. Comparisons were conducted of the dimensional developmental phenotype of 22q11.2DS and sibling controls. For autistic traits, both parents and children were phenotyped using the Social Responsiveness Scale. Results Young children with 22q11.2DS exhibited large impairments (Hedge's g ≥ 0.8) across a range of developmental domains relative to sibling controls, as well as high rates of transdiagnostic neurodevelopmental and psychiatric traits. Cluster analysis revealed a subgroup of children with 22q11.2DS (n = 16; 53%) in whom neurodevelopmental and psychiatric liability was particularly increased and who differed from other children with 22q11.2DS and non-carrier siblings. Exploratory analyses revealed that early motor and sleep impairments indexed liability for neurodevelopmental and psychiatric outcomes. Maternal autism trait scores were predictive of autism traits in children with 22q11.2DS (intraclass correlation coefficients = 0.47, p = 0.046, n = 31). Conclusions Although psychiatric conditions typically emerge later in adolescence and adulthood in 22q11.2DS, our exploratory study was able to identify a range of early risk indicators. Furthermore, findings indicate the presence of a subgroup who appeared to have increased neurodevelopmental and psychiatric liability. Our findings highlight the scope for future studies of early risk mechanisms and early intervention within this high genetic risk patient group

Management of nystagmus in children: A review of the literature and current practice in UK specialist services

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods