A multiplexed human papillomavirus (HPV) 16 and 18 diagnostic for cervical cancer screening

Cervical cancer is a major problem in the developing world and low- resource settings where standard screening techniques are not accessible. Cervical cancer is one of the few cancers that can be successfully treated when detected early. Therefore, there exists a high clinical need to screen for cervical cancer early. The etiological agent of cervical cancer is the human papillomavirus (HPV), with 70% of cases related to HPV genotypes 16 and 18. I sought to increase access to screening by developing a fully integrated and multiplexed molecular diagnostic assay to extract, amplify, detect, and distinguish HPV16 and HPV18 DNA on a low-cost paperfluidic platform for point- of-care (POC) applications. Isothermal (one temperature) loop-mediated amplification (LAMP) was used to amplify HPV DNA instead of the traditional polymerase chain reaction (PCR) that requires multiple temperatures. The amplified HPV16 and HPV18 DNA were differentially detected on a simple lateral flow strip – similar to that used in a pregnancy test – generating a visible colorimetric readout for each specific genotype. LAMP amplification is difficult to characterize and current methods were insufficient in providing specificity at the level needed for a multiplexed assay. Therefore, a novel characterization strategy was developed based on fluorescence to distinguish positive LAMP amplification products. This workflow used differential fluorescent tags to identify whether HPV16 DNA or HPV18 DNA was present and simplified complex nonspecific LAMP smears to a specific band pattern. After singleplex HPV16 and HPV18 LAMP assays were optimized with the new workflow, the two singleplex assays were successfully combined into one multiplex reaction with 12 primers, a nontrivial feat. Each assay step – DNA extraction, amplification, and detection – was optimized and integrated into a single chip that can control the timing of each step. Several chip configurations were tested to determine the optimal chip form factor, and a small subset of clinical samples were tested to demonstrate feasibility in low-resource settings. With this diagnostic platform, asymptomatic patients positive for HPV16 DNA and HPV18 DNA can be screened more closely, allocating precious resources to those most at risk, a beneficial use in both low-resource settings and the USA

A fully integrated paperfluidic molecular diagnostic chip for the extraction, amplification, and detection of nucleic acids from clinical samples

Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples through immunoassays; however, the detection of many disease targets relies on the much higher sensitivity and specificity achieved via nucleic acid amplification tests (NAAT). The steps involved in NAAT have recently begun to be explored in paper matrices, and our group, among others, has reported on paper-based extraction, amplification, and detection of DNA and RNA targets. Here, we integrate these paper-based NAAT steps into a single paperfluidic chip in a modular, foldable system that allows for fully integrated fluidic handling from sample to result. We showcase the functionality of the chip by combining nucleic acid isolation, isothermal amplification, and lateral flow detection of human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in less than 1 hour for rapid, early detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, and offering the potential for a point-of-care molecular diagnostic platform even in remote and resource-limited settings.U54 EB015403 - NIBIB NIH HHS; U54 EB015408 - NIBIB NIH HHS; U54-EB015403-S1 - NIBIB NIH HH

The associations of body mass index with physical and mental aspects of health-related quality of life in Chinese patients with type 2 diabetes mellitus: Results from a cross-sectional survey

Background: This study aimed to determine the associations of various clinical factors with generic health-related quality of life (HRQOL) scores among Hong Kong Chinese patients with type 2 diabetes mellitus (T2DM) in the outpatient primary care setting using the short-form 12 (SF-12).Methods: A cross-sectional survey of 488 Chinese adults with T2DM recruited from a primary care outpatient clinic was conducted from May to August 2008. Data on the standard Chinese (HK) SF-12 Health Survey and patients' socio-demographics were collected from face-to-face interviews. Glycaemic control, body mass index (BMI), chronic co-morbidities, diabetic complications and treatment modalities were determined for each patient through medical records. Associations of socio-demographic and clinical factors with physical component summary (PCS-12) and mental component summary scores (MCS-12) were evaluated using multiple linear regression.Results: The socio-demographic correlates of PCS-12 and MCS-12 were age, gender and BMI. After adjustment for socio-demographic variables, the BMI was negatively associated with PCS-12 but positively associated with MCS-12. The presence of diabetic complications was associated with lower PCS-12 (regression coefficient:-3.0 points, p < 0.05) while being on insulin treatment was associated with lower MCS-12 (regression coefficient:-5.8 points, p < 0.05). In contrast, glycaemic control, duration of T2DM and treatment with oral hypoglycaemic drugs were not significantly associated with PCS-12 or MCS-12.Conclusions: Among T2DM subjects in the primary care setting, impairments in the physical aspect of HRQOL were evident in subjects who were obese or had diabetic complications whereas defects in the mental aspect of HRQOL were observed in patients with lower BMI or receiving insulin injections. © 2013 Wong et al.; licensee BioMed Central Ltd.published_or_final_versio

Using Latent Class Analyses to Examine Health Disparities among Young Children in Socially Disadvantaged Families during the COVID-19 Pandemic

Rising income inequality is strongly linked to health disparities, particularly in regions where uneven distribution of wealth and income has long been a concern. Despite emerging evidence of COVID-19-related health inequalities for adults, limited evidence is available for children and their parents. This study aimed to explore subtypes of families of preschoolers living in the disadvantaged neighborhoods of Hong Kong based on patterns of family hardship and to compare their patterns of parenting behavior, lifestyle practices, and wellbeing during the COVID-19 pandemic. Data were collected from 1338 preschoolers and their parents during March to June 2020. Latent class analysis was performed based on 11 socioeconomic and disease indicators. Multivariate logistic regressions were used to examine associations between identified classes and variables of interest during the COVID-19 pandemic. Four classes of family hardship were identified. Class 1 (45.7%) had the lowest disease and financial burden. Class 2 (14.0%) had the highest financial burden. Class 3 (5.9%) had the highest disease burden. Class 4 (34.5%) had low family income but did not receive government welfare assistance. Class 1 (low hardship) had lower risks of child maltreatment and adjustment problems than Class 2 (poverty) and Class 3 (poor health). However, children in Class 1 (low hardship) had higher odds of suffering psychological aggression and poorer physical wellbeing than those in Class 4 (low income), even after adjusting for child age and gender. The findings emphasize the need to adopt flexible intervention strategies in the time of large disease outbreak to address diverse problems and concerns among socially disadvantaged families

Evidence of individual differences in the long-term social, psychological, and cognitive consequences of child maltreatment

Background: The prevalence and consequences of child maltreatment are alarming, but evidence from studies with long follow-up intervals are limited. This study examined the long-term consequences of child maltreatment in relation to age of onset and follow-up interval. / Methods: The exposed group comprised 63 individuals (aged 13–34 years) with a first-time diagnosis of child maltreatment between 2001 and 2010, whereas the unexposed group comprised 63 individuals who were matched upon gender, age of onset, follow-up period, and poverty status at the index hospital admission but had no medical records of maltreatment in Hong Kong. The participants completed a set of questionnaires on executive functions and mental health and provided blood samples for measurement of IL-6 and IL-10 levels during a health assessment session. / Results: Compared with the unexposed group, the exposed group reported poorer maternal care during childhood (β = −4.64, p < 0.001) and had lower family support (β = −2.97, p = 0.010) and higher inflammatory responses (IL-6: β = 0.15, p = 0.001; IL-10: β = 0.11, p = 0.011) at follow-up. Additionally, the associations of childhood maltreatment exposure with family support and maternal care differed by age of onset and the length of time since exposure. / Conclusions: This matched cohort study highlights childhood maltreatment as a risk factor for systemic inflammation and an indicator of suboptimal social environment, both of which could persist over a long period of time

Electronic Structure, Pore Size Distribution, and Sorption Characterization of an Unusual MOF, {[Ni(dpbz)][Ni(CN)\u3csub\u3e4\u3c/sub\u3e]}n, dpbz = 1,4-bis(4-pyridyl)benzene

The monoclinic (Ni(L)[Ni(CN)4] (L= 1,4-Bis(4-pyridyl) benzene) compound (defined as Ni-dpbz) is a flexible metal organic framework which assumes a pillared structure with layers defined by 2D Ni[Ni(CN)4]n nets and dpbz ligands as pillars. The structure features an entrapped dpbz ligand that links between the open ends of four-fold Ni sites from two neighboring chains. This arrangement results in an unusual 5-fold pseudo square-pyramid environment for Ni and a significantly long Ni-N distance of 2.369(4) Å. Using Density Functional Theory calculations, the different bonding characteristics between the 5-fold and 6-fold Ni\u27s were determined. We found that there is weak covalent bonding between the 5-fold Ni and N in the entrapped ligand, and the 6-fold Ni-N bonds provide effective electronic conduction. The disordered dimethyl sulfoxide (DMSO) solvent molecules are not bonded to the framework. The material has a single pore with a diameter of 4.1 Å. This pore includes approximately 55% of the total free volume (based on a zero-diameter probe). The accessible pore surface area and pore volume were calculated to be 507 m2/g and 6.99 cm3/kg, respectively. The maximum amount of CO2 that can be accommodated in the pores after DMSO is removed was found to be 204 mg/g, agreeing with the results of adsorption/desorption experiments of about 220 mg/g

Renal screening in children after exposure to low dose melamine in Hong Kong: cross sectional study

Objective To investigate the renal outcomes of children after exposure to low dose melamine in Hong Kong

A Longitudinal Study of the Relation between Childhood Activities and Psychosocial Adjustment in Early Adolescence

Background: Although an increasing body of research shows that excessive screen time could impair brain development, whereas non-screen recreational activities can promote the development of adaptive emotion regulation and social skills, there is a lack of comparative research on this topic. Hence, this study examined whether and to what extent the frequency of early-life activities predicted later externalizing and internalizing problems. Methods: In 2012/13, we recruited Kindergarten 3 (K3) students from randomly selected kindergartens in two districts of Hong Kong and collected parent-report data on children’s screen activities and parent–child activities. In 2018/19, we re-surveyed the parents of 323 students (aged 11 to 13 years) with question items regarding their children’s externalizing and internalizing symptoms in early adolescence. Linear regression analyses were conducted to examine the associations between childhood activities and psychosocial problems in early adolescence. Results: Early-life parent–child activities (β = −0.14, p = 0.012) and child-alone screen use duration (β = 0.15, p = 0.007) independently predicted externalizing problems in early adolescence. Their associations with video game exposure (β = 0.19, p = 0.004) and non-screen recreational parent–child activities (β = −0.14, p = 0.004) were particularly strong. Conclusions: Parent–child play time is important for healthy psychosocial development. More efforts should be directed to urge parents and caregivers to replace child-alone screen time with parent–child play time

Prospective Study on Retinal Nerve Fibre Layer Thickness Changes in Isolated Unilateral Retrobulbar Optic Neuritis

Purpose. To investigate the retinal nerve fibre layer (RNFL) thickness after unilateral acute optic neuritis using optical coherence tomography (OCT). Patients and Methods. This prospective cohort study recruited consecutive patients with a first episode of isolated, unilateral acute optic neuritis. RNFL thickness and visual acuity (VA) of the attack and normal fellow eye were measured at presentation and 3 months in both the treatment and nontreatment groups. Results. 11 subjects received systemic steroids and 9 were treated conservatively. The baseline RNFL thickness was similar in the attack and fellow eye (P≥0.4). At 3 months, the attack eye had a thinner temporal (P=0.02) and average (P=0.05) RNFL compared to the fellow eye. At 3 months, the attack eye had significant RNFL thinning in the 4 quadrants and average thickness (P≤0.0002) compared to baseline. The RNFL thickness between the treatment and nontreatment groups was similar at baseline and 3 months (P≥0.1). Treatment offered better VA at 3 months (0.1 ± 0.2 versus 0.3 ± 0.2 LogMAR, P=0.04). Conclusion. Generalized RNFL thinning occurred at 3 months after a first episode of acute optic neuritis most significantly in the temporal quadrant and average thickness. Visual improvement with treatment was independent of RNFL thickness

Promoting resilience for HIV prevention in female sex workers in Hong Kong: a randomised controlled trial

Background: Female sex workers are considered a reservoir of HIV and their psychological health has a role to play in HIV infections. In China, commercial sex workers were reported to account for nearly 50% of heterosexual transmission of HIV. Therefore, HIV prevention targeted at mental health could be an innovative strategy in controlling the infection. We aimed to provide an evidence-based resilience-promoting intervention targeting mental health and ultimately safe sexual practices of female sex workers. Methods: This randomised controlled trial was done at three Hong Kong non-governmental organisations, namely Action for REACH OUT, JJJ Association, and the Society of Rehabilitation and Crime Prevention. Participants in this study were women (aged ≥18 years) who had worked as a sex worker in the previous 6 months. We randomly assigned participants to either intervention or usual care (control) according to a predetermined, computer-generated randomisation list. Both group facilitator and partcipants were unmasked to the group allocation, but an independent researcher who was masked to the treatment allocation administered the questionnaires. About half of the participants were permanent residents of Hong Kong whereas the other half were from mainland China. The six-session resilience-promoting intervention was designed to improve the coping skills, self-esteem, and self-efficacy (i.e. the belief of an individuals’ ability to control their actions to achieve desired goal), as measured by Brief-COPE, the Rosenberg Self-esteem Scale, and the Generalised Self- efficacy Scale of female sex workers. Questionnaires were administered by an independent assessor at baseline, post-treatment, and at 3-months follow-up. Participants in the control group received standard service, which included outreach visits, screening for HIV or sexually transmitted infections, and social activities provided by non-governmental organisations. The primary outcome of this study was the resilience scores measured by Connor-Davidson Resilience Scale. We analysed the differences between the two groups using the intention-to-treat analysis. This study was approved by the University of Hong Kong/Hospital Authority Hong Kong West Cluster Internal Review Board (UW 12-220). Verbal informed consent was obtained from all participants. Findings: 127 female sex workers were randomly assigned: 64 joined the control group and 63 joined intervention group. There were significant differences on the score on resilience, self-esteem, and mental health status between groups at post-intervention and 3- month follow-up. We found that condom use in the intervention group at 3-month follow-up was improved compared with the control group. After controlling for marital status and family size, improved resilience scores were associated with intervention group assignment (odds ratio 2∙95 [95% CI 1∙19–7∙35]; p=0∧021) and self-efficacy (1∧13 [1∧03–1∧24]; p=0∧006). Interpretation: Our findings suggest that resilience-promoting intervention programme was effective in improving the mental health status among Chinese female sex workers. This programme is an innovative approach to HIV prevention by promoting both psychological well-being and safe sex for this high-risk population. Funding: Council for the AIDS Trust Fund and General Research Grant, Research Grants Council, HKSAR