Publications

This article describes a 3D microfluidic paper-based analytical device that can be used to conduct an enzyme-linked immunosorbent assay (ELISA). The device comprises two parts: a sliding strip (which contains the active sensing area) and a structure surrounding the sliding strip (which holds stored reagents—buffers, antibodies, and enzymatic substrate—and distributes fluid). Running an ELISA involves adding sample (e.g. blood) and water, moving the sliding strip at scheduled times, and analyzing the resulting color in the sensing area visually or using a flatbed scanner. We demonstrate that this device can be used to detect C-reactive protein (CRP)—a biomarker for neonatal sepsis, pelvic inflammatory disease, and inflammatory bowel diseases—at a concentration range of 1–100 ng/mL in 1000-fold diluted blood (1–100 µg/mL in undiluted blood). The accuracy of the device (as characterized by the area under the receiver operator characteristics curve) is 89% and 83% for cut-offs of 10 ng/mL (for neonatal sepsis and pelvic inflammatory disease) and 30 ng/mL (for inflammatory bowel diseases) CRP in 1000-fold diluted blood respectively. In resource-limited settings, the device can be used as a part of a kit (containing the device, a fixed-volume capillary, a pre-filled tube, a syringe, and a dropper); this kit would cost ~ $0.50 when produced in large scale (>100,000 devices/week). This kit has the technical characteristics to be employed as a pre-screening tool, when combined with other data such as patient history and clinical signs. • 3D microfluidic paper-based analytical device performs ELISA with colorimetric results. • Two components enable separation of reagents in the device: a sliding-strip and a functional dock. • All required reagents (antibodies, enzyme, substrate, buffers) are stored in the device. • User only needs to add sample and water using the provided kit. • Device can detect C-reactive protein for possible pre-screening of neonatal sepsis, pelvic inflammatory disease, or inflammatory bowel diseases.

ABSTRACT Background Both statins and PCSK9 inhibitors lower blood low-density lipoprotein cholesterol (LDL-C) levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these two lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial, and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial. Methods 228 circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5,359 individuals (2,659 on treatment) in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial at 6-months post-randomization. The corresponding metabolic measures were analyzed in eight population cohorts (N=72,185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. Results Scaled to an equivalent lowering of LDL-C, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy ( R 2 =0.88). Alterations in lipoprotein lipid composition and fatty acid balance were similar. However, discrepancies were observed for very-low-density lipoprotein (VLDL) lipid measures. For instance, genetic inhibition of PCSK9 showed weaker effects on lowering of VLDL-cholesterol compared with statin therapy (54% vs. 77% reduction, relative to the lowering effect on LDL-C; P =2 × 10 −7 for heterogeneity). Genetic inhibition of PCSK9 showed no robust effects on amino acids, ketones, and a marker of inflammation (GlycA); in contrast, statin treatment lowered GlycA levels. Conclusions Genetic inhibition of PCSK9 results in similar metabolic effects as statin therapy across a detailed lipid and metabolite profile. However, for the same lowering of LDL-C, PCSK9 inhibitors are predicted to be less efficacious than statins at lowering VLDL lipids, which could potentially translate into subtle differences in cardiovascular risk reduction.

The adhesion between thin elastic films/coatings and ductile substrates can be measured using a wedge test, wherein a long sharp edge is impressed through the film into the substrate. The resulting plastic deformation causes delamination between the film and the substrate. The extent of the delamination can be correlated with the crack driving force to determine the toughness of the interface. Results are presented that relate the energy release rate and mode-mixity to the stresses: both residual and those induced by the impression. Numerical and asymptotic results are presented for the strain transferred to the coating. The numerical results verify that the asymptotics provide accurate closed-form solutions when the delaminations exceed about seven contact widths. An example is provided for a thermal barrier coating system.

Predicting 10-year mortality in older adults using VO2max, oxygen uptake efficiency slope and frailty class Erik Fung, Erik Fung Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARLaboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, and Gerald Choa Cardiac Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARCARE Programme, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK Corresponding author. Erik Fung, 9/F, Lui Che Woo Clinical Sciences Building, Department of Medicine and Therapeutics, CUHK, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. Email: e.fung@cuhk.edu.hk Search for other works by this author on: Oxford Academic Google Scholar Leong Ting Lui, Leong Ting Lui Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARLaboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, and Gerald Choa Cardiac Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARCARE Programme, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR Search for other works by this author on: Oxford Academic Google Scholar Finn Gustafsson, Finn Gustafsson Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar Forrest C F Yau, Forrest C F Yau Centre for Nutritional Studies, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR Search for other works by this author on: Oxford Academic Google Scholar Jason C S Leung, Jason C S Leung CUHK Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR Search for other works by this author on: Oxford Academic Google Scholar Petri Wiklund, Petri Wiklund Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UKFaculty of Medicine, University of Oulu, FinlandFaculty of Sport Sciences, University of Jyväskylä, FinlandThe Exercise Translational Medicine Centre, Shanghai Jiao Tong University, People's Republic of China Search for other works by this author on: Oxford Academic Google Scholar Marjo-Riitta Järvelin, Marjo-Riitta Järvelin Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UKFaculty of Medicine, University of Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar Peter S Macdonald, Peter S Macdonald Heart and Lung Transplant Unit, St Vincent's Hospital, University of New South Wales, AustraliaTransplantation Research Laboratory, Victor Chang Cardiac Research Institute, Australia Search for other works by this author on: Oxford Academic Google Scholar Jean Woo Jean Woo Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SARCUHK Jockey Club Institute of Ageing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR Search for other works by this author on: Oxford Academic Google Scholar European Journal of Preventive Cardiology, Volume 28, Issue 10, October 2021, Pages 1148–1151, https://doi.org/10.1177/2047487320914435 Published: 31 March 2020

We describe a three-dimensional magnetic twisting device that is useful in characterizing the mechanical properties of cells. With the use of three pairs of orthogonally aligned coils, oscillatory mechanical torque was applied to magnetic beads about any chosen axis. Frequencies up to 1 kHz could be attained. Cell deformation was measured in response to torque applied via an RGD-coated, surface-bound magnetic bead. In both unpatterned and micropatterned elongated cells on extracellular matrix, the mechanical stiffness transverse to the long axis of the cell was less than half that parallel to the long axis. Elongated cells on poly-l-lysine lost stress fibers and exhibited little mechanical anisotropy; disrupting the actin cytoskeleton or decreasing cytoskeletal tension substantially decreased the anisotropy. These results suggest that mechanical anisotropy originates from intrinsic cytoskeletal tension within the stress fibers. Deformation patterns of the cytoskeleton and the nucleolus were sensitive to loading direction, suggesting anisotropic mechanical signaling. This technology may be useful for elucidating the structural basis of mechanotransduction.

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

No abstract is provided for this article.

ABSTRACT Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5,485 women with GDM and 347,856 without GDM. Through trans-ancestry meta-analysis, we identified five loci with genome-wide significant association ( p <5×10 −8 ) with GDM, mapping to/near MTNR1B ( p =4.3×10 −54 ), TCF7L2 ( p =4.0×10 −16 ), CDKAL1 ( p =1.6×10 −14 ), CDKN2A-CDKN2B ( p =4.1×10 −9 ) and HKDC1 ( p =2.9×10 −8 ). Multiple lines of evidence pointed to genetic contributions to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1 ) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.

No abstract is provided for this article.

OBJECTIVE: Problems with language and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood and adolescence are often strongly linked to low scholastic performance. Early recognition of children who are at increased risk is necessary. Our objective was to determine whether mixed-handedness, which is associated with atypical cerebral laterality, is associated with language, scholastic, and ADHD symptoms in childhood and adolescence. METHODS: Prospective data come from the Northern Finland Birth Cohort 1986, a longitudinal, population-based birth cohort with assessments when children were 7 to 8 and 16 years of age (N = 7871). Teacher, parent, and/or adolescent reports were used to assess language difficulties, scholastic performance, and mental health, including ADHD symptoms. RESULTS: Mixed-handed children, relative to right-handed, had approximately a twofold increase in odds of having difficulties with language and scholastic performance at the age of 8 years. Eight years later, as 16-year-olds, adolescents had twofold increase in odds concerning difficulties in school with language and with ADHD symptoms. Mixed-handed children were more likely to have scores indicating probable psychiatric disturbance, including ADHD symptoms. As adolescents, mixed-handed children with previous behavioral problems were at considerably higher risk for scoring within the range of probable ADHD-inattention or ADHD-combined case. Mixed-handedness was associated with greater symptom severity in children and adolescents (P = .01) concerning psychiatric disturbance and ADHD inattention but not ADHD hyperactivity. CONCLUSIONS: The results indicate that mixed-handed children have a greater likelihood of having language, scholastic, and mental health problems in childhood and that these persist into adolescence. Thus, these results suggest that mixed-handedness, particularly in the presence of difficulties, could aid in the recognition of children who are at risk for stable problems. Additional research is needed to understand the connections between neural substrates related to atypical cerebral asymmetry, mixed-handedness, and mental health problems including ADHD symptoms.

The development of a multifunctional device that achieves optogenetic neuromodulation and extracellular neural mapping is crucial for understanding neural circuits and treating brain disorders. Although various devices have been explored for this purpose, it is challenging to develop biocompatible optogenetic devices that can seamlessly interface with the brain. Herein, we present a tissue-like optoelectronic mesh with a compact interface that enables not only high spatial and temporal resolutions of optical stimulation but also the sampling of optically evoked neural activities. An in vitro experiment in hydrogel showed efficient light propagation through a freestanding SU-8 waveguide that was integrated with flexible mesh electronics. Additionally, an in vivo implantation of the tissue-like optoelectronic mesh in the brain of a live transgenic mouse enabled the sampling of optically evoked neural signals. Therefore, this multifunctional device can aid the chronic modulation of neural circuits and behavior studies for developing biological and therapeutic applications.