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1.  Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis 
Cell Stress & Chaperones  2013;18(5):535-558.
O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a ubiquitous and dynamic post-translational modification known to modify over 3,000 nuclear, cytoplasmic, and mitochondrial eukaryotic proteins. Addition of O-GlcNAc to proteins is catalyzed by the O-GlcNAc transferase and is removed by a neutral-N-acetyl-β-glucosaminidase (O-GlcNAcase). O-GlcNAc is thought to regulate proteins in a manner analogous to protein phosphorylation, and the cycling of this carbohydrate modification regulates many cellular functions such as the cellular stress response. Diverse forms of cellular stress and tissue injury result in enhanced O-GlcNAc modification, or O-GlcNAcylation, of numerous intracellular proteins. Stress-induced O-GlcNAcylation appears to promote cell/tissue survival by regulating a multitude of biological processes including: the phosphoinositide 3-kinase/Akt pathway, heat shock protein expression, calcium homeostasis, levels of reactive oxygen species, ER stress, protein stability, mitochondrial dynamics, and inflammation. Here, we will discuss the regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage. We will also discuss the misregulation of O-GlcNAc in diseases commonly associated with the stress response, namely Alzheimer’s and Parkinson’s diseases. Finally, we will highlight recent advancements in the tools and technologies used to study the O-GlcNAc modification.
doi:10.1007/s12192-013-0426-y
PMCID: PMC3745259  PMID: 23620203
O-GlcNAc; Stress; Signal transduction; O-GlcNAc transferase; O-GlcNAcase; Post-translational modification
2.  Cross-Sectional Study on Attitudes among General Practitioners towards Pneumococcal Vaccination for Middle-Aged and Elderly Population in Hong Kong 
PLoS ONE  2013;8(11):e78210.
Objective
To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50–64) and elderly population (over 65) in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups.
Design
Cross-sectional study of general practitioners in private practice in Hong Kong.
Participants
Members of Hong Kong Medical Association delivering general practice services in private sector.
Measuring Tool
Self-administered questionnaire.
Main Outcome Measures
Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination.
Results
53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%). Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1), and attending 6 pneumonia cases or more per year (ORm 2.28) were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41), consultation not related to vaccination (ORm 0.45) and limited time (ORm 0.38) were factors that reduced the likelihood.
Conclusion
Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.
doi:10.1371/journal.pone.0078210
PMCID: PMC3818320  PMID: 24223775
3.  Evaluation of the Sustaining Effects of Tai Chi Qigong in the Sixth Month in Promoting Psychosocial Health in COPD Patients: A Single-Blind, Randomized Controlled Trial 
The Scientific World Journal  2013;2013:425082.
Objectives. To evaluate the sustaining effects of Tai Chi Qigong (TCQ) in improving the psychosocial health in chronic obstructive pulmonary disease (COPD) patients in the sixth month. Background. COPD affects both physical and emotional aspects of life. Measures to minimize patients' suffering need to be implemented. Methods. 206 COPD patients were randomly assigned into three groups: TCQ group, exercise group, and control group. The TCQ group completed a three-month TCQ program, the exercise group practiced breathing and walking exercise, and the control group received usual care. Results. Significant group-by-time interactions in quality of life (QOL) using St. George's respiratory questionnaire (P = 0.002) and the perceived social support from friends using multidimensional scale of perceived social support (P = 0.04) were noted. Improvements were observed in the TCQ group only. Conclusions. TCQ has sustaining effects in improving psychosocial health; it is also a useful and appropriate exercise for COPD patients.
doi:10.1155/2013/425082
PMCID: PMC3824309  PMID: 24282383
4.  Knowledge, Attitude, Practice and Barriers on Vaccination against Human Papillomavirus Infection: A Cross-Sectional Study among Primary Care Physicians in Hong Kong 
PLoS ONE  2013;8(8):e71827.
This study explored the knowledge, attitude, practice and barriers to prescribe human papillomavirus (HPV) vaccines among private primary care physicians in Hong Kong. A self-administered questionnaire survey was conducted by sending letters to doctors who had joined a vaccination program for school girls. From 720 surveys sent, 444 (61.7%) completed questionnaires were returned and analyzed. For knowledge, few responded to questions accurately on the prevalence of cervical HPV (27.9%) and genital wart infection (13.1%) among sexually active young women in Hong Kong, and only 44.4% correctly answered the percentage of cervical cancers caused by HPV. For attitude, most agreed that HPV vaccination should be fully paid by the Government (68.3%) as an important public health strategy. Vaccination against HPV was perceived as more important than those for genital herpes (52.2%) and Chlamydia (50.1%) for adolescent health, and the majority selected adolescents aged 12–14 years as the ideal group for vaccination. Gardasil® (30.9%) and Cervarix® (28.0%) were almost equally preferred. For practice, the factors influencing the choice of vaccine included strength of vaccine protection (61.1%), long-lasting immunity (56.8%) and good antibody response (55.6%). The most significant barriers to prescribe HPV vaccines consisted of parental refusal due to safety concerns (48.2%), and their practice of advising vaccination was mostly affected by local Governmental recommendations (78.7%). A substantial proportion of physicians had recommended HPV vaccines for their female clients/patients aged 18–26 years for protection of cervical cancer (83.8%) or both cervical cancer and genital warts (85.5%). The knowledge on HPV infection was low among physicians in Hong Kong. Prescription of HPV vaccine was hindered by the perceived parental concerns and was mostly relied on Governmental recommendations. Educational initiatives should be targeted towards both physicians and parents, and the Government should consider full subsidy to enhance vaccine uptake rate.
doi:10.1371/journal.pone.0071827
PMCID: PMC3749199  PMID: 23990994
5.  Correction: Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development 
PLoS Pathogens  2013;9(8):10.1371/annotation/f8e7c7e3-c347-4243-9146-db77900cb90c.
doi:10.1371/annotation/f8e7c7e3-c347-4243-9146-db77900cb90c
PMCID: PMC3752017
6.  Human Vocal Attractiveness as Signaled by Body Size Projection 
PLoS ONE  2013;8(4):e62397.
Voice, as a secondary sexual characteristic, is known to affect the perceived attractiveness of human individuals. But the underlying mechanism of vocal attractiveness has remained unclear. Here, we presented human listeners with acoustically altered natural sentences and fully synthetic sentences with systematically manipulated pitch, formants and voice quality based on a principle of body size projection reported for animal calls and emotional human vocal expressions. The results show that male listeners preferred a female voice that signals a small body size, with relatively high pitch, wide formant dispersion and breathy voice, while female listeners preferred a male voice that signals a large body size with low pitch and narrow formant dispersion. Interestingly, however, male vocal attractiveness was also enhanced by breathiness, which presumably softened the aggressiveness associated with a large body size. These results, together with the additional finding that the same vocal dimensions also affect emotion judgment, indicate that humans still employ a vocal interaction strategy used in animal calls despite the development of complex language.
doi:10.1371/journal.pone.0062397
PMCID: PMC3634748  PMID: 23638065
7.  Nonamnestic Presentations of Early-Onset Alzheimer’s Disease 
Early-onset Alzheimer’s disease (EOAD) beginning before the age of 65 may differ from late-onset AD (LOAD) in clinical course and frequency of nonamnestic presentations. In a 10-year retrospective review, 125 patients with EOAD, diagnosed clinically and verified by functional neuroimaging, were compared with 56 patients with LOAD and further classified depending on predominant cognitive difficulty on presentation. Eighty (64%) of the patients with EOAD had a nonamnestic presentation, compared with only 7 (12.5%) of the patients with LOAD. Compared with LOAD, the patients with EOAD had a shorter duration with lower Mini-Mental State Examination scores. The neuroimaging reports among the patients with EOAD showed more hippocampal atrophy with an amnestic presentation, more left parietal changes with impaired language presentations, and more right parietal and occipital changes with impaired visuospatial presentations. These findings indicate that EOAD differs from LOAD in a more aggressive course and in having predominantly nonamnestic presentations that vary in neuropathological location.
doi:10.1177/1533317512454711
PMCID: PMC3625669  PMID: 22871906
Alzheimer’s disease; early-onset; aphasia; posterior cortical atrophy; apraxia
8.  Development of Peptide Nucleic Acid Probes for Detection of the HER2 Oncogene 
PLoS ONE  2013;8(4):e58870.
Peptide nucleic acids (PNAs) have gained much interest as molecular recognition tools in biology, medicine and chemistry. This is due to high hybridization efficiency to complimentary oligonucleotides and stability of the duplexes with RNA or DNA. We have synthesized 15/16-mer PNA probes to detect the HER2 mRNA. The performance of these probes to detect the HER2 target was evaluated by fluorescence imaging and fluorescence bead assays. The PNA probes have sufficiently discriminated between the wild type HER2 target and the mutant target with single base mismatches. Furthermore, the probes exhibited excellent linear concentration dependence between 0.4 to 400 fmol for the target gene. The results demonstrate potential application of PNAs as diagnostic probes with high specificity for quantitative measurements of amplifications or over-expressions of oncogenes.
doi:10.1371/journal.pone.0058870
PMCID: PMC3622650  PMID: 23593123
9.  The Impact of Leadership Programme on Self-Esteem and Self-Efficacy in School: A Randomized Controlled Trial 
PLoS ONE  2012;7(12):e52023.
Background
Leadership training programs by experiential learning among adolescents are very popular worldwide and in particular developed countries, but there exists few studies which formally assessed their impact on the psychological well-being of program participants. This study evaluated the effectiveness of leadership training programs on self-esteem and self-efficacy among adolescents.
Methodology/Principal Findings
a total of 180 students of the same grade of one secondary school were randomized into an intervention (n = 50) and a control group (n = 130). The students in the intervention group participated in a 6-month program of leadership training and service learning, while the control group did not participate in any training. Their self-esteem and self-efficacy were assessed by Rosenberg Self-Esteem questionnaire and Chinese Adaptation of the General Self-Efficacy Scale, respectively, before and after the program. Both scales have been recognized internationally as valid and reliable survey instruments to measure these psychological attributes. The scores were compared by Student’s tests according to gender. A total of 180 students were enrolled during the study period October, 2009 to May, 2010. Their mean age was 15.18 years (0.62) and 56.7% were male. Students allocated to the intervention and control group had statistically similar demographic characteristics except gender (male 36.0% vs. 64.6%, p = 0.001). Overall, the self-esteem scores increased by 1.28 and decreased by 0.30 (p = 0.161) while the self-efficacy scores increased by 0.26 and decreased by 0.76 (p = 0.429) in the intervention and control group, respectively. Among female students, the intervention group showed significant improvements in both self-esteem (2.38 vs. −0.24, p<0.001) and self-efficacy (1.32 vs. –0.04, p = 0.043).
Conclusions/Significance
Leadership training program were not found to be effective to enhance self-esteem and self-efficacy in adolescents, except girls who showed modest increase in these outcomes. Future research should assess the reasons why these programs are effective among female.
doi:10.1371/journal.pone.0052023
PMCID: PMC3525562  PMID: 23272199
10.  Synthesis of novel cyclic NGR/RGD peptide analogs via on resin click chemistry 
Targeted drug deliveries as well as high resolution imaging of cancerous tissues and organs via specific cancer cell markers have become important in chemotherapeutic interventions of cancer treatment. Short peptides such as RGD and NGR are showing promising results for targeted drug delivery and in vivo imaging. We have applied on resin Huisgen's 1,3-dipolar cycloaddition to synthesize new cyclic RGD and NGR peptide analogs. Preliminary binding assays of these new analogs by fluorescence polarization indicates specific binding to purified CD13 (Aminopeptidase N) and cell lysates from MCF-7 and SKOV-3 cancer cell lines.
doi:10.1016/j.bmcl.2010.10.064
PMCID: PMC3472425  PMID: 21050757
11.  Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease 
Journal of neurology  2012;259(10):2182-2188.
Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.
doi:10.1007/s00415-012-6481-y
PMCID: PMC3442121  PMID: 22460587
Dementia; Early onset Alzheimer’s disease; Familial Alzheimer’s disease; PSEN1 gene
12.  Communication between Corneal Epithelial Cells and Trigeminal Neurons Is Facilitated by Purinergic (P2) and Glutamatergic Receptors 
PLoS ONE  2012;7(9):e44574.
Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2) receptors resulting in mobilization of a Ca2+ wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca2+ wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca2+ mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca2+ mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca2+ waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA) receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.
doi:10.1371/journal.pone.0044574
PMCID: PMC3436752  PMID: 22970252
13.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia 
Brain  2011;134(9):2456-2477.
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
doi:10.1093/brain/awr179
PMCID: PMC3170532  PMID: 21810890
behavioural variant frontotemporal dementia; diagnostic criteria; frontotemporal lobar degeneration; FTD; pathology
14.  Intracellular recording in behaving animals 
Electrophysiological recordings from behaving animals provide an unparalleled view into the functional role of individual neurons. Intracellular approaches can be especially revealing as they provide information about a neuron’s inputs and intrinsic cellular properties, which together determine its spiking output. Recent technical developments have made intracellular recording possible during an ever-increasing range of behaviors in both head-fixed and freely moving animals. These recordings have yielded fundamental insights into the cellular and circuit mechanisms underlying neural activity during natural behaviors in such areas as sensory perception, motor sequence generation, and spatial navigation, forging a direct link between cellular and systems neuroscience.
doi:10.1016/j.conb.2011.10.013
PMCID: PMC3408887  PMID: 22054814
15.  Intracellular determinants of hippocampal CA1 place and silent cell activity in a novel environment 
Neuron  2011;70(1):109-120.
Summary
For each environment a rodent has explored, its hippocampus contains a map consisting of a unique subset of neurons, called place cells, that have spatially-tuned spiking there, with the remaining neurons being essentially silent. Using whole-cell recording in freely moving rats exploring a novel maze, we observed differences in intrinsic cellular properties and input-based subthreshold membrane potential levels underlying this division into place and silent cells. Compared to silent cells, place cells had lower spike thresholds and peaked versus flat subthreshold membrane potentials as a function of animal location. Both differences were evident from the beginning of exploration. Additionally, future place cells exhibited higher burst propensity before exploration. Thus, internal settings appear to predetermine which cells will represent the next novel environment encountered. Furthermore, place cells fired spatially-tuned bursts with large, putatively calcium-mediated depolarizations that could trigger plasticity and stabilize the new map for long-term storage. Our results provide new insight into hippocampal memory formation.
doi:10.1016/j.neuron.2011.03.006
PMCID: PMC3221010  PMID: 21482360
16.  Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development 
PLoS Pathogens  2011;7(9):e1002198.
The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.
Author Summary
C. trachomatis is the leading cause of non-congenital blindness in developing countries and is the number one cause of sexually transmitted disease and non-congenital infertility in Western countries. The capacity of Chlamydia infections to lead to infertility and blindness, their association with chronic diseases, and the extraordinary prevalence and array of these infections make them public concerns of primary importance. This pathogen must establish a protective membrane-bound niche and acquire essential lipids from the host cell during infection in order to survive and replicate. This study identifies novel mechanisms by which C. trachomatis hijacks various lipid trafficking proteins for distinct roles during intracellular development. Disruption of these lipid trafficking pathways results in alterations in the growth and stability of its protective niche as well as a defect in replication. Understanding the molecular mechanisms of these host-pathogen interactions will lead to rational approaches for the development of novel therapeutics, diagnostics, and preventative strategies.
doi:10.1371/journal.ppat.1002198
PMCID: PMC3164637  PMID: 21909260
18.  Facing the threat of influenza pandemic - roles of and implications to general practitioners 
BMC Public Health  2010;10:661.
The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by theWHO, H1N1 (2009) virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS) in Hong Kong has shown that general practitioners (GPs) were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs.
There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza.
In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care level. The health care system would thus remain sustainable during the public health crisis.
doi:10.1186/1471-2458-10-661
PMCID: PMC2988738  PMID: 21044300
19.  Automated screening for mutants affecting dopaminergic neuron specification in C. elegans 
Nature methods  2008;5(10):869-872.
We describe an automated method to isolate mutant C. elegans animals, which fail to appropriately execute a cellular differentiation program that we monitor with gfp-based reporter gene technology. A fluorescence activated sorting mechanism implemented in the COPAS Biosort machine is able to isolate mutants with subtle alterations in the cellular specificity of gfp expression. This methodology is significantly more efficient than comparable manual screens and enabled us to isolate mutants in which dopamine neurons fail to differentiate appropriately.
doi:10.1038/nmeth.1250
PMCID: PMC2693092  PMID: 18758453
20.  Can Health Promoting Schools contribute to the better health and wellbeing of young people? The Hong Kong experience 
Background
The Health Promoting School (HPS) is a WHO sponsored framework, compiled to enable education and health sectors to be more effective in school based initiatives.
Aims
This study attempted to test the hypothesis that students from schools that had comprehensively embraced the HPS concept as indicated by the Healthy School Award, were better, in terms of health risk behaviour, self reported health status, and academic results, than students from schools that did not reach the standard of the award.
Methods and Results
The results presented came from nine schools (four primary and five secondary) applying for accreditation of the Healthy Schools Award after adopting the HPS framework for two years. Regular consultancy support and training were available to all schools. Students had completed before and after surveys to assess their health behaviours, self reported health status, and academic standing before the two year intervention, and at its end. Data from the before and after surveys of the students attending schools that reached certain level of HPS standard as indicated by the award, were compared with students whose schools did not receive the award, and the results showed differences. Some differences were found to be more significant among the primary school students than secondary schools students. This illustrated early intervention for lifestyle changes to be more effective. Students' satisfaction with life also improved if their schools adopted the concept of HPS comprehensively.
Conclusions
The results suggest that comprehensive implementation of HPS would contribute to differences in certain behaviours and self reported health and academic status.
doi:10.1136/jech.2005.040121
PMCID: PMC2563946  PMID: 16698986
wellbeing; Health Promotion Schools
21.  Novel Low Abundance and Transient RNAs in Yeast Revealed by Tiling Microarrays and Ultra High–Throughput Sequencing Are Not Conserved Across Closely Related Yeast Species 
PLoS Genetics  2008;4(12):e1000299.
A complete description of the transcriptome of an organism is crucial for a comprehensive understanding of how it functions and how its transcriptional networks are controlled, and may provide insights into the organism's evolution. Despite the status of Saccharomyces cerevisiae as arguably the most well-studied model eukaryote, we still do not have a full catalog or understanding of all its genes. In order to interrogate the transcriptome of S. cerevisiae for low abundance or rapidly turned over transcripts, we deleted elements of the RNA degradation machinery with the goal of preferentially increasing the relative abundance of such transcripts. We then used high-resolution tiling microarrays and ultra high–throughput sequencing (UHTS) to identify, map, and validate unannotated transcripts that are more abundant in the RNA degradation mutants relative to wild-type cells. We identified 365 currently unannotated transcripts, the majority presumably representing low abundance or short-lived RNAs, of which 185 are previously unknown and unique to this study. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts. Of the 185 transcripts we identified as novel to our study, greater than 80 percent come from regions of the genome that have lower conservation scores amongst closely related yeast species than 85 percent of the verified ORFs in S. cerevisiae. Such regions of the genome have typically been less well-studied, and by definition transcripts from these regions will distinguish S. cerevisiae from these closely related species.
Author Summary
The budding yeast Saccharomyces cerevisiae, because of the relative ease of its genetic manipulation and its ease of handling in the laboratory, has long served as a model on which studies in higher organisms have been based. To more fully understand how eukaryotic cells express their genomes, we sought to identify RNA species that are transcribed at very low levels or that are rapidly degraded. We created mutants deficient in the ability to degrade RNA, with the expectation that this would increase the relative abundance of such RNAs, and then used high-resolution microarrays and sequencing technologies to locate and identify from where these RNAs are transcribed. Using this approach, we have identified 365 transcripts that do not appear in the most current list of annotated S. cerevisiae RNA transcripts; of these, 185 are unique to our study. Many of these novel transcripts derive from regions of the genome that are poorly conserved between S. cerevisiae and other closely related yeast species, suggesting that these RNAs may play an important role in the divergent microevolution of S. cerevisiae.
doi:10.1371/journal.pgen.1000299
PMCID: PMC2601015  PMID: 19096707
22.  Can the concept of Health Promoting Schools help to improve students' health knowledge and practices to combat the challenge of communicable diseases: Case study in Hong Kong? 
BMC Public Health  2008;8:42.
Background
The growing epidemics of emerging infectious diseases has raised the importance of a setting approach and include the Health Promoting School (HPS) framework to promote better health and hygiene. Built on the concept of 'the' HPS framework, the Hong Kong Healthy Schools Award scheme includes "Personal Health Skills" as one of its key aspects to improve student hygiene knowledge and practices. This study examines the differences in student perceptions, knowledge and health behaviours between those schools that have adopted the HPS framework and those that have not adopted.
Methods
A cross-sectional study using multi-stage random sampling was conducted among schools with awards (HSA) and those schools not involved in the award scheme nor adopting the concept of HPS (non-HPS). For HSA group, 5 primary schools and 7 secondary schools entered the study with 510 students and 789 students sampled respectively. For the 'Non-HPS' group, 8 primary schools and 7 secondary schools entered the study with 676 students and 725 students sampled respectively. A self-administered questionnaire was used as the measuring instrument.
Results
Students in the HSA category were found to be better with statistical significance in personal hygiene practice, knowledge on health and hygiene, as well as access to health information. HSA schools were reported to have better school health policy, higher degrees of community participation, and better hygienic environment.
Conclusion
Students in schools that had adopted the HPS framework had a more positive health behaviour profile than those in non-HPS schools. Although a causal relationship is yet to be established, the HPS appears to be a viable approach for addressing communicable diseases.
doi:10.1186/1471-2458-8-42
PMCID: PMC2258284  PMID: 18234083
23.  Improving Health and Building Human Capital Through an Effective Primary Care System 
To improve population health, one must put emphasis on reducing health inequities and enhancing health protection and disease prevention, and early diagnosis and treatment of diseases by tackling the determinants of health at the downstream, midstream, and upstream levels. There is strong theoretical and empirical evidence for the association between strong national primary care systems and improved health indicators. The setting approach to promote health such as healthy schools, healthy cities also aims to address the determinants of health and build the capacity of individuals, families, and communities to create strong human and social capitals. The notion of human and social capitals begins to offer explanations why certain communities are unable to achieve better health than other communities with similar demography. In this paper, a review of studies conducted in different countries illustrate how a well-developed primary health care system would reduce all causes of mortalities, improve health status, reduce hospitalization, and be cost saving despite a disparity in socioeconomic conditions. The intervention strategy recommended in this paper is developing a model of comprehensive primary health care system by joining up different settings integrating the efforts of different parties within and outside the health sector. Different components of primary health care team would then work more closely with individuals and families and different healthy settings. This synergistic effect would help to strengthen human and social capital development. The model can then combine the efforts of upstream, midstream, and downstream approaches to improve population health and reduce health inequity. Otherwise, health would easily be jeopardized as a result of rapid urbanization.
doi:10.1007/s11524-007-9175-5
PMCID: PMC1891639  PMID: 17356902
Health improvement; Human capital; Primary health care.
24.  Improving Health and Building Human Capital Through an Effective Primary Care System 
To improve population health, one must put emphasis on reducing health inequities and enhancing health protection and disease prevention, and early diagnosis and treatment of diseases by tackling the determinants of health at the downstream, midstream, and upstream levels. There is strong theoretical and empirical evidence for the association between strong national primary care systems and improved health indicators. The setting approach to promote health such as healthy schools, healthy cities also aims to address the determinants of health and build the capacity of individuals, families, and communities to create strong human and social capitals. The notion of human and social capitals begins to offer explanations why certain communities are unable to achieve better health than other communities with similar demography. In this paper, a review of studies conducted in different countries illustrate how a well-developed primary health care system would reduce all causes of mortalities, improve health status, reduce hospitalization, and be cost saving despite a disparity in socioeconomic conditions. The intervention strategy recommended in this paper is developing a model of comprehensive primary health care system by joining up different settings integrating the efforts of different parties within and outside the health sector. Different components of primary health care team would then work more closely with individuals and families and different healthy settings. This synergistic effect would help to strengthen human and social capital development. The model can then combine the efforts of upstream, midstream, and downstream approaches to improve population health and reduce health inequity. Otherwise, health would easily be jeopardized as a result of rapid urbanization.
doi:10.1007/s11524-007-9175-5
PMCID: PMC1891639  PMID: 17356902
Health improvement; Human capital; Primary health care.

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