Validation and application of health utilities index in Chinese subjects with down syndrome

Objectives: The objectives of the study were (1) to validate the Chinese version of Health Utilities Index (HUI-Ch); (2) to examine the Health-related Quality of Life (HRQoL) of Chinese subjects with Down syndrome (DS); and (3) to study the impact of chronic health conditions on HRQoL of Chinese with DS. Methods: The multiple choice questionnaire for scoring Health Utilities Index Mark 2 (HUI2) and Health Utilities Index Mark 3 (HUI3) was translated and validated. In addition to the HRQoL scores from HUI2 and HUI3, proxy-data on socio-demographics, and 10 common chronic health conditions for people with DS were collected and analyzed. Data analysis involves multiple imputation and multiple regression analysis to predict variations in HRQoL in relation to different factors. Lastly, a gradient interval was constructed on the number of chronic health conditions in relation to HRQoL. Results: HUI-Ch was validated according to standard guidelines. People with DS were found to have a lower HRQoL as compared to the general population, with the majority categorized as moderate or severe on the scale. Behavioral and hearing problems on HUI2, and hearing problems on HUI3 were found to be statistically significant predictors of a lower HRQoL score. A significant gradient relationship existed showing when the number of health problems increased, the HRQoL scores decreased. Conclusions: HUI-Ch is a valid instrument to assess HRQoL. It can have broad application in Chinese subjects with DS including the study of the impact of different chronic health conditions on their quality of life. The quantifiable nature of HUI-Ch will facilitate longitudinal study on the well-being of subjects with DS and evaluation of effectiveness of intervention programs in the near future

New record of the Japanese seahorse Hippocampus mohnikei Bleeker, 1853 (Syngnathiformes: Syngnathidae) in Hong Kong waters

Funding: This study was supported by the Consultancy Project (AFCD/SQ/13/17) of the Agriculture, Fisheries and Conservation Department of the Government of the Hong Kong SAR and the Collaborative Research Fund (C7013-19G) of the Hong Kong Research Grants Council.A new record of Hippocampus mohnikei Bleeker, 1853 was confirmed in Hong Kong through morphological and molecular identification. It is highly possible that there is an established population of H. mohnikei in Hong Kong due to continuous sightings by citizen scientists in the past nine years. The record is significant from a biogeographical perspective as it connects the distributions of known populations in northern China and Japan to those spanning Thailand to India. This further affirms the status of Hong Kong as a hotspot for seahorse biodiversity and conservation in China.Publisher PDFPeer reviewe

Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis

IntroductionAdolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case–control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS.MethodsThe study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle <6°). Clinical and radiological assessments were conducted on each group.ResultsCobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p < 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011).DiscussionPatients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression

Sleep problems in children with autism spectrum disorder in Hong Kong: a cross-sectional study

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with a growing prevalence of sleep problems associated with significant behavioral problems and more severe autism clinical presentation. Little is known about the relationships between autism traits and sleep problems in Hong Kong. Therefore, this study aimed to examine whether children with autism have increased sleep problems than non-autistic children in Hong Kong. The secondary objective was to examine the factors associated with sleep problems in an autism clinical sample.MethodsThis cross-sectional study recruited 135 children with autism and 102 with the same age range of non-autistic children, aged between 6 and 12 years. Both groups were screened and compared on their sleep behaviors using the Children's Sleep Habits Questionnaire (CSHQ).ResultsChildren with autism had significantly more sleep problems than non-autistic children [t(226.73) = 6.20, p < 0.001]. Bed -sharing [beta = 0.25, t(165) = 2.75, p = 0.07] and maternal age at birth [beta = 0.15, t(165) = 2.05, p = 0.043] were significant factors associated with CSHQ score on the top of autism traits. Stepwise linear regression modeling identified that only separation anxiety disorder (beta = 4.83, t = 2.40, p = 0.019) best-predicted CSHQ.ConclusionIn summary, autistic children suffered from significantly more sleep problems and co-occurring separation anxiety disorder brings greater sleep problems as compared to non-autistic children. Clinicians should be more aware of sleep problems to provide more effective treatments to children with autism

MicroRNA clusters integrate evolutionary constraints on expression and target affinities : the miR-6/5/4/286/3/309 cluster in Drosophila

This research was supported by the Hong Kong Research Grant Council GRF Grant (14103516), The Chinese University of Hong Kong Direct Grant (4053248), and TUYF Charitable Trust (6903957) (JHLH).A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs.PostprintPeer reviewe

Speak-up culture in an intensive care unit in Hong Kong: a cross-sectional survey exploring the communication openness perceptions of Chinese doctors and nurses

Objectives Despite growing recognition of the importance of speaking up to protect patient safety in critical care, little research has been performed in this area in an intensive care unit (ICU) context. This study explored the communication openness perceptions of Chinese doctors and nurses and identified their perceptions of issues in ICU communication, their reasons for speaking up and the possible factors and strategies involved in promoting the practice of speaking up. Design A mixed-methods design with quantitative and sequential qualitative components was used. Setting and participants Eighty ICU staff members from a large public hospital in Hong Kong completed a questionnaire regarding their perceptions of communication openness. Ten clinicians whose survey responses indicated support for open communication were then interviewed about their speak-up practices. Results The participating ICU staff members had similar perceptions of their openness to communication. However, the doctors responded more positively than the nurses to many aspects of communication openness. The two groups also had different perceptions of speaking up. The interviewed ICU staff members who indicated a high level of communication openness reported that their primary reasons for speaking up were to seek and clarify information, which was achieved by asking questions. Other factors perceived to influence the motivation to speak up included seniority, relationships and familiarity with patient cases. Conclusions Creating an atmosphere of safety and equality in which team members feel confident in expressing their personal views without fear of reprisal or embarrassment is necessary to encourage ICU staff members, regardless of their position, to speak up. Because harmony and saving face is valued in Chinese culture, training nurses and doctors to speak up by focusing on human factors and values rather than simply addressing conflict management is desirable in this context.This work was supported by funding from the Hospital Authority’s Kowloon Central Cluster Research Grant (grant number: KCC/RC/G/1516-B03)

Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells

Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data