Art Therapy Approach to Burnout Reduction for Hospice and Palliative Care Workers

Poster Presentation: no. SPP-P8.29Conference Theme: Enhancing Health - 協作同心‧醫澤社群published_or_final_versio

Sedlin and prostaglandin E2 dehydrogenase - interactions and implications for spondyloepiphyseal dysplasia tarda

Session D - Genomic Disorders: abstract no. D020Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked, late-onset skeletal disease. Affected individuals develop phenotypes in their early childhood, displaying barrel-shaped chests, vertebral bodies malformation, flattened disc spaces and premature osteoarthritis in weight-bearing joints. The disease was found linked to the gene SEDL coding for the protein sedlin. Sedlin is one of the subunits of the TRAPP (Transport Protein Particle) complex, which is responsible for vesicle tethering during endoplasmic reticulum-to-golgi transport. Although sedlin is known to function in intracellular trafficking, the reason why mutations in a trafficking protein lead to a skeletal disease remains unknown. To address this, four missense mutations (D47Y, S73L, F83S and V130D) of sedlin observed in SEDT patients were studied. Except D47Y, the other three mutations cause proteosomal degradation of sedlin in cultured cells, whereas the D47Y mutation had a minor effect on Bet3 binding to sedlin. Pull-down assay was performed to identify novel sedlin interacting partners. 15-hydroxyprostaglandin dehydrogenase (PGDH) was pulled down and the interaction was confirmed in cell culture system. Sedlin activates PGDH activity in vitro. By confocal microscopy, sedlin was also found to colocalize with PGDH in the cytosol. PGDH catalyzes the degradation of prostaglandin E2, which affects cartilage and bone growth. Further investigation is ongoing to understand the function of sedlin and the mechanism of disease for SEDT.postprintThe 1st International Congress on Research of Rare and Orphan Diseases (RE(ACT) 2012), Basel, Switzerland, 29 February-2 March 2012. In Brochure of RE(ACT)® 2012, 2012, p. 11

Harvesting convalescent plasma for hyperimmune intravenous globulin production: a multicentre randomised double-blind controlled trial for treatment of patients with serious S-OIV H1N1 infection

Poster Presentations: Emerging / Infectious Diseases: abstract no. P107-Ab0089Symposium Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Harvesting convalescent plasma for hyperimmune intravenous globulin production: a multicentre randomised double-blind controlled trial for treatment of patients with serious S-OIV H1N1 infection

Poster Presentations: Emerging / Infectious Diseases: abstract no. P107-Ab0089Symposium Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong

Background. Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory tract infections in children. We conducted the first systematic prospective clinical and molecular study using nasopharyngeal aspirates (NPAs) and fecal samples. Methods. NPAs negative for influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, and coronavirus and fecal samples from patients with acute gastroenteritis were included. On the basis of results from a pilot study using 400 NPAs from all age groups, a prospective 12-month study was conducted to detect HBoV in 1200 NPAs and 1435 fecal samples from patients <18 years old by polymerase chain reaction. The complete genome sequences of HBoVs from 12 NPAs and 12 fecal samples were determined. Results. Of the 400 NPAs collected in the pilot study, 20 (5.0%) were found to contain HBoV, all from children <5 years old. In the subsequent prospective study of pediatric patients, HBoV was detected in 83 (6.9%) of 1200 NPAs. Upper and lower respiratory tract infections were equally common. HBoV was detected in 30 (2.1%) of 1435 fecal samples. Fever and watery diarrhea were the most common symptoms. The seasonality of HBoV in NPAs and fecal samples was similar. Codetection with other pathogens occurred in 33% and 56% of NPAs and fecal samples, respectively, from patients with HBoV infection. Genomes of HBoVs from NPAs and fecal samples displayed minimal sequence variations. Conclusions. HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Access and Unmet Needs of Orphan Drugs in 194 Countries and Six Areas: a Global Policy Review with Content Analysis

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs$3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs

Wild type and mutant 2009 pandemic influenza A (H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice

Background: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. Principal Findings: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. Conclusion: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation. © 2010 Chan et al.published_or_final_versio

De novo large rare copy-number variations contribute to conotruncal heart disease in Chinese patients

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Diagnostic value of whole-exome sequencing in Chinese pediatric-onset neuromuscular patients

BACKGROUND: Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with a broad spectrum of overlapping the clinical presentations that makes diagnosis challenging. Notably, the recent introduction of whole-exome sequencing (WES) is introducing rapid changes on the genetic diagnosis of NMDs. We aimed to investigate the diagnostic value of WES for pediatric-onset NMDs. METHODS: We applied integrated diagnostic approach and performed WES in 50 Chinese subjects (30 males, 20 females) with undiagnosed pediatric-onset NMDs despite previous specific tests. The patients were categorized in four subgroups according to phenotyping and investigation findings. Variants on NMDs gene list and open exome analysis for those with initial negative findings were identified. RESULTS: WES identified causative variants in ACTA1 (n = 2), POMT1, COL6A1 (n = 2), MTMR2, LMNA, SELENON, DNM2, TGFB1, MPZ, IGHMBP2, and LAMA2 in 13 patients. Two subjects have variants of uncertain significance (VUSs) in TTN and SCN11A, unlikely to be pathogenic due to incompatible phenotypes. The mean interval time from symptom onset to genetic diagnosis was 10.4 years (range from 1 month to 33 years). The overall diagnostic yield of WES in our cohort was 26%. Open exome analysis was necessary to identify the pathogenic variant in TGFB1 that caused skeletal dysplasia with neuromuscular presentation. CONCLUSION: Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs

Genome-Wide DNA Methylation Analysis of Chinese Patients with Systemic Lupus Erythematosus Identified Hypomethylation in Genes Related to the Type I Interferon Pathway

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