Vivian Yawei Guo

Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.

Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

Development of a Health Empowerment Programme to improve the health of working poor families: protocol for a prospective cohort study in Hong Kong.

Introduction People from working poor families are at high risk of poor health partly due to limited healthcare access. Health empowerment, a process by which people can gain greater control over the decisions affecting their lives and health through education and motivation, can be an effective way to enhance health, health-related quality of life (HRQOL), health awareness and health-seeking behaviours of these people. A new cohort study will be launched to explore the potential for a Health Empowerment Programme to enable these families by enhancing their health status and modifying their attitudes towards health-related issues. If proven effective, similar empowerment programme models could be tested and further disseminated in collaborations with healthcare providers and policymakers. Method and analysis A prospective cohort study with 200 intervention families will be launched and followed up for 5 years. The following inclusion criteria will be used at the time of recruitment: (1) Having at least one working family member; (2) Having at least one child studying in grades 1–3; and (3) Having a monthly household income that is less than 75% of the median monthly household income of Hong Kong families. The Health Empowerment Programme that will be offered to intervention families will comprise four components: health assessment, health literacy, self-care enablement and health ambassador. Their health status, HRQOL, lifestyle and health service utilisation will be assessed and compared with 200 control families with matching characteristics but will not receive the health empowerment intervention. Ethics and dissemination This project was approved by the University of Hong Kong—the Hospital Authority Hong Kong West Cluster IRB, Reference number: UW 12-517. The study findings will be disseminated through a series of peer-reviewed publications and conference presentations, as well as a yearly report to the philanthropic funding body–Kerry Group Kuok Foundation (Hong Kong) Limited.

Prospective Association between Diabetic Retinopathy and Cardiovascular Disease—A Systematic Review and Meta-analysis of Cohort Studies

BACKGROUND Diabetic retinopathy (DR) is linked to increased risk of cardiovascular (CV) disease. However, the effect size of the association was not consistent. In this study, we performed a systematic review and meta-analysis of available cohort studies to determine the association between DR and CV disease, and to investigate the factors that influence the association. METHODS Terms related to DR and CV disease were searched from MEDLINE and EMBASE database. High-quality articles (Newcastle-Ottawa scales above 6) conducted in cohort studies reporting the association between DR and CV disease were identified. Study-specific estimates were pooled using random effects with inverse variance meta-analysis. Subgroup analysis was performed according to diabetes types. Heterogeneity of included studies was assessed using the I(2) test. The cause of the heterogeneity was examined using metaregression analyses. RESULTS A total of 13 studies representing 17,611 patients without CV disease at baseline were included. At follow-up, there were 1457 CV disease-related incidences. Overall, DR was associated with increased risk of CV disease (relative risk [RR]: 2.42, 95% confidence interval [CI]: 1.77-3.31) in diabetes. Specifically, the RR was 3.59 (95% CI: 1.79-7.20) for type 1 diabetes and 1.81 (95% CI: 1.47-2.23) for type 2 diabetes. Significant heterogeneity was found in studies with type 1 diabetes. Metaregression analysis showed that baseline systolic blood pressure was a key factor leading to the heterogeneity. CONCLUSION In conclusion, DR is significantly associated with CV disease incidence and CV disease-related mortality in diabetes. Patients with DR may need more intensive management to control future CV disease attacks.

Aquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate astrocytes in mouse☆ , ☆☆

BACKGROUND Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorder. Up to 90% of patients are seropositive for aquaporin-4 autoantibodies (AQP4 Ab). The pathogenetic mechanisms underlying clinical onset and relapse of NMO are uncertain. OBJECTIVE Study the pathogenicity of AQP4 Ab in the absence of complement activation. METHODS Female C57BL/6N mice (human IgG cannot activate mouse complements) pretreated with complete Freunds adjuvant (CFA, day 0) and pertussis toxin (PTx, day 0 and day 2) were transferred with IgG isolated from serum of healthy subjects or NMO patients (AQP4 Ab-positive or negative) intraperitoneally (day 7-9). Mice were observed for signs of experimental autoimmune encephalomyelitis (EAE) by standard 6-grade EAE scores. Spinal cord was obtained at day 11 for immunohistochemistry. RESULTS None of the mice had clinical signs of encephalomyelitis, inflammatory cells infiltration or demyelination of spinal cord. CFA and PTx induce BBB breakdown evidenced by leakage of human IgG into cord parenchyma. Patchy areas of AQP4 loss were observed in spinal cord of mice transferred with IgG from AQP4 Ab-positive NMO patients but not in mice transferred with IgG from AQP4 Ab-negative NMO patients or healthy subjects; but there was no loss of glial fibrillary acidic protein immunoreactivity in all mice. Markedly increased proliferation of astrocytic processes suggestive of astrocytic activation was observed in mice transferred with IgG from AQP4 Ab-positive patients. CONCLUSION AQP4 Ab cause asymptomatic AQP4 loss and astrocytic activation but not myelitis, demyelination or astrocytic cytotoxicity in spinal cord of mouse in the absence of complement activation.

Cost-effectiveness analysis of vaccinations and decision makings on vaccination programmes in Hong Kong: A systematic review

OBJECTIVES To describe and systematically review the modelling and reporting of cost-effectiveness analysis of vaccination in Hong Kong, and to identify areas for quality enhancement in future cost-effectiveness analyses. METHODS We conducted a comprehensive and systematic review of cost-effectiveness studies related to vaccination and government immunisation programmes in Hong Kong published from 1990 to 2015, through database search of Pubmed, Web of Science, Embase, and OVID Medline. Methodological quality of selected studies was assessed using Consolidated Health Economic Evaluation Reporting Standards checklist (CHEERS). Decision making of vaccination was obtained from Scientific Committee on Vaccine Preventable Diseases (SCVPD) and Department of Health in Hong Kong. RESULTS Nine eligible studies reporting twelve comparative cost-effectiveness comparisons of vaccination programme for influenza (n=2), pneumococcal disease (n=3), influenza plus pneumococcal disease (n=1), chickenpox (n=2), Haemophilus influenzae b (n=1), hepatitis A (n=1), cervical cancer (n=1) and rotavirus (n=1) were identified. Ten comparisons (83.3%) calculated the incremental cost-effectiveness ratio (ICER) of a vaccination strategy versus status quo as outcomes in terms of cost in USD per life-years, cost per quality-adjusted life-years, or cost per disability-adjusted life-years. Among those 10 comparisons in base-case scenario, 4 evaluated interventions were cost-saving relative to status quo while the ICER estimates in 3 of the 6 remaining comparisons were far below commonly accepted threshold and WHO willingness-to-pay threshold, suggestive of very cost-effective. Seven studies were of good quality based on the CHEERS checklist; one was of moderate quality; and one was of excellent quality. The common methodological problems were characterisation of heterogeneity and reporting of study parameters. CONCLUSIONS There was a paucity of cost-effectiveness models evaluating vaccination targeted to the Hong Kong population. All evaluated vaccinations and immunisation interventions in Hong Kong, except for Haemophilus influenzae b, hepatitis A and HPV vaccinations, were considered either cost-saving or very cost-effective when compared to status quo.

Poverty and health-related quality of life of people living in Hong Kong: comparison of individuals from low-income families and the general population

Background To assess health-related quality of life (HRQOL) among Chinese adults from low-income households in Hong Kong, and to explore any threshold of household income that impaired HRQOL. Methods A cross-sectional analysis was conducted on 298 adults from low-income families when they enrolled into a cohort study between 2012 and 2014. HRQOL was measured by the 12-item Short-Form Health Survey-version 2 (SF-12v2). Their mean SF-12v2 subscale and summary scores were compared with those of 596 age-sex-matched subjects randomly selected from a database of 2763 adults from the Hong Kong general population (ratio = 1:2). Multiple linear regressions were conducted to determine any association between monthly household income and HRQOL. Results Subjects from low-income households had significantly lower SF-12v2 bodily pain, general health, vitality and physical component summary (PCS) scores than the age-sex matched subjects from the general population. Subgroup analysis showed that a household income <50% of the median monthly household income in Hong Kong (HK

Fetuin-A levels and risk of type 2 diabetes mellitus: a systematic review and meta-analysis

10 000 ≈ US

Mothers’ health-related quality of life: Its relationship with children’s health-related quality of life and behavior in low-income families

1290, i.e. poverty line in Hong Kong) was independently associated with poorer PCS and mental component summary (MCS) scores after adjustment for socio-demographics and co-morbidities. Conclusion Chinese adults from low-income households had poorer HRQOL, and <50% of the median monthly household income seems to be the threshold for impairment of both physical and mental HRQOL. The findings support the current definition of the poverty line.

Maternal mental quality of life mediates the associations between intimate partner abuse against mothers and their children’s behaviours and quality of life in low-income Chinese families

AimsFetuin-A has been linked to insulin resistance and obesity. Its role in the pathogenesis of type 2 diabetes (T2DM) has also been discussed. We aimed to investigate the prospective association of fetuin-A and the risk of T2DM in a systematic review and meta-analysis.MethodsA systematic search of studies from the MEDLINE, EMBASE, Pubmed and Web of Science using fetuin-A, diabetes and various synonyms was conducted up to June 5, 2017. Relevant studies were extracted by two reviewers independently. The quality of studies was assessed using Newcastle–Ottawa scales. Overall estimates were pooled using fixed effect with inverse variance meta-analysis. Subgroup analyses by gender, study population, techniques of assessing fetuin-A, diabetes ascertainment methods, follow-up duration and measures of association were conducted.ResultsSeven studies comprising a total of 11,497 individuals and 2176 cases of T2DM were included in the systematic review and meta-analysis. Overall, one SD increment of fetuin-A level was associated with a 23% greater risk of incident T2DM (RR: 1.23, 95% CI 1.16–1.31). No significant heterogeneity or publication bias was found. The association was relatively stable across different subgroups. However, the association seemed only evident in women, but not in men.ConclusionsHigher circulating fetuin-A levels were associated with increased risk of T2DM. However, the causality deserved further analysis.

A prospective cohort study to investigate parental stress and child health in low-income Chinese families: protocol paper

Objective To examine the association between mothers’ health-related quality of life (HRQOL) and their children’s HRQOL and behavior in low-income families. Methods Mothers of 278 children aged 6–12 years from low-income families were invited to complete the Child Health Questionnaire Parent Form 50 (CHQ-PF50) and the Strength and Difficulties Questionnaire (SDQ) for their children as well as the 12-item Short-Form Health Survey version 2 (SF-12v2) and the Patient Health Questionnaire-2 (PHQ-2). Multiple linear regressions with mother–child pairs as the unit of analysis were performed to examine the associations between maternal and child variables with adjustment of mother- and child-level confounders. Results Compared with the general population, low-income mothers had a lower mean SF-12v2 mental component summary score and their children also had lower mean CHQ-PF50 physical and psychosocial summary scores and SDQ total difficulties score. Children of mothers with SF-12v2 scores below the population mean of 50 had significantly worse CHQ-PF50 scores and higher SDQ total difficulties scores. The mother’s PHQ-2 depression status had no association with the child’s CHQ-PF50 scores. Conclusion Our findings suggest that more attention should be paid to reducing the negative impact of health problems on mothers’ daily roles in childcare in low-income families.