High frequency ultrasound assessment of skin fibrosis : clinical results

Author name used in this publication: Y. P. HuangAuthor name used in this publication: Y. P. ZhengAuthor name used in this publication: S. F. LeungAuthor name used in this publication: A. P. C. Choi2007-2008 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Ultrasound palpation sensor for tissue thickness and elasticity measurement - assessment of transverse carpal ligament

Author name used in this publication: Y. P. ZhengAuthor name used in this publication: A. P. C. ChoiAuthor name used in this publication: M. H. LuAuthor name used in this publication: X. ChenAuthor name used in this publication: Q. H. Huang2006-2007 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Investigating poultry trade patterns to guide avian influenza surveillance and control: a case study in Vietnam

Live bird markets are often the focus of surveillance activities monitoring avian influenza viruses (AIV) circulating in poultry. However, in order to ensure a high sensitivity of virus detection and effectiveness of management actions, poultry management practices features influencing AIV dynamics need to be accounted for in the design of surveillance programmes. In order to address this knowledge gap, a cross-sectional survey was conducted through interviews with 791 traders in 18 Vietnamese live bird markets. Markets greatly differed according to the sources from which poultry was obtained, and their connections to other markets through the movements of their traders. These features, which could be informed based on indicators that are easy to measure, suggest that markets could be used as sentinels for monitoring virus strains circulating in specific segments of the poultry production sector. AIV spread within markets was modelled. Due to the high turn-over of poultry, viral amplification was likely to be minimal in most of the largest markets. However, due to the large number of birds being introduced each day, and challenges related to cleaning and disinfection, environmental accumulation of viruses at markets may take place, posing a threat to the poultry production sector and to public health

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Clinical management guidelines for osteoporosis in Hong Kong

The following guidelines provide a basis for the management of osteoporosis for the practising physician in Hong Kong. The guidelines have been complied by a working group that represents the specialties concerned with osteoporosis and summarise the current management of osteoporosis based on available published evidence and relevant local experience.published_or_final_versio

Optimization of ex vivo hematopoietic stem cell expansion in intermittent dynamic cultures

For the ex vivo expansion of CD34+ cells, culture conditions were optimized using cytokine cocktails and media change methods. In addition, static, orbital-shake, and stirred cultures were compared. After cultivation, total cell expansion, immunophenotypes, clonogenic ability, and metabolite concentration in media were analyzed. Optimized media change methods enhanced the number of total nucleated cells (TNCs) by 600-fold (from 104 to 6 × 106 cells) in static cultures. Furthermore, intermittent orbital-shake cultures gave the highest fold increase of TNCs and CD34+/CD38− cells. These results imply that proliferation of CD34+ cells in intermittent shake cultures was more efficient than that in static cultures under optimized culture conditions

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion