An observational study of pediatric healthcare burden in Angelman syndrome: results from a real-world study.

BACKGROUND:The objective of this study is to describe variations in the healthcare resource utilization (HRU) among individuals with Angelman syndrome (AS) over the first 12 years of life. Data for this study were drawn from the AS Natural History study (ASNHS), which is an observational study on the developmental progress, behavior, and medical morbidity of individuals with AS conducted over eight years. Caregiver-reported information on hospitalization, surgery, and medication utilization was used to assess HRU. Repeated measures mixed effect models were used to assess the relationship between age and probability of hospitalization, surgery, and prescription medication utilization. RESULTS:Mean age at study enrollment was 6 years of age and both sexes were equally represented. The mean number of visits per participant was three. Results from this study suggest that individuals with AS have a high HRU burden. Hospitalization and surgery burden were highest in the first year of life. Use of medications for seizures and sleep disturbance increased over time. CONCLUSIONS:The study highlights the significant healthcare burden among individuals with AS. Future studies that estimate cost and caregiver burden associated with AS are needed to assess the lifelong economic impact of AS on families and healthcare system

X-linked Malformation and Infantile Lethality Syndrome (provisionally named Ogden Syndrome)

This is a lethal X-linked disorder of infancy comprising a distinct combination of distinctive craniofacial features producing an aged appearance, growth failure, hypotonia, global developmental delays, cryptorchidism, and acquired cardiac arrhythmias. The first family was identified in Ogden, Utah, with five affected boys in two generations of family members. A mutation was identified as a c.109T>C(p.Ser37Pro) variant in NAA10, a gene encoding the catalytic subunit of the major human N-terminal acetyltransferase (NatA). This same mutation was identified in a second unrelated family, with three affected boys in two generations. This X-linked Malformation and Infantile Lethality Syndrome has provisionally been named Ogden Syndrome, in honor of the hometown where the first family resides

A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome.

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.ResultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.ConclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatment studies.Trial registrationNCT00348933 . Registered 6 July 2006

Social Marketing

Social marketing is receiving unprecedented focus and support from government, the private sector and charities internationally. Social marketing attempts to educate people in the hope that they will make 'informed'(i.e. healthy) choices regarding diet, lifestyle and health related issues. The effective application of social marketing principles can be complex and controversial. Social marketing planning cannot be reduced to a simple set of actions on a checklist; there is no single strategy for success and strategies that have proved successful with one population may not transfer to other populations. This text will explore the complexities involved in researching, planning and implementing effective social marketing programmes, using illustrative cases from both successful and unsuccessful real-world programmes. The authors provide a critical analysis of the origins of social marketing as a concept and of the claims made by its supporters and detractors in order to highlight what social marketing can and cannot achieve. This is followed by a review of strategic issues that must be considered in developing social marketing programmes, including persuasion resistance, message relevance and message framing. Key themes included in the text are the impact of cultural factors on health-related behaviours, ethical issues and attitudes as a key factor underlying health-related behaviours. The authors introduce concepts, theories and strategies that will aid the development, testing and implementation of social marketing interventions. The book is suitable for both undergraduate and postgraduate students of business and marketing and those studying modules in social marketing

The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43

Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP