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The severity of COVID-19 infections could be exacerbated by the epidemic of chronic diseases and underlying inequalities in social determinants of health. Nonetheless, there is scanty evidence in regions with a relatively well-controlled outbreak. This study examined the socioeconomic patterning of COVID-19 severity and its effect modification with multimorbidity in Hong Kong. 3074 local COVID-19 cases diagnosed from 5 July to 31 October 2020 were analyzed and followed up until 30 November 2020. Data on residential addresses, socio-demographic background, COVID-19 clinical conditions, and pre-existing chronic diseases of confirmed cases were retrieved from the Centre for Health Protection and the Hospital Authority. Results showed that, despite an independent adverse impact of multimorbidity on COVID-19 severity (aOR = 2.35 [95% CI = 1.72-3.19]), it varied across the socioeconomic ladder, with no significant risk among those living in the wealthiest areas (aOR = 0.80 [0.32-2.02]). Also, no significant association of the area-level income-poverty rate with severe COVID-19 was observed. In conclusion, the socioeconomic patterning of severe COVID-19 was mild in Hong Kong. Nonetheless, socioeconomic position interacted with multimorbidity to determine COVID-19 severity with a mitigated risk among the socioeconomically advantaged. Plausible explanations include the underlying socioeconomic inequalities in chronic disease management and the equity impact of the public-private dual-track healthcare system.

Objectives: To assess the prevalence of potentially inappropriate medication (PIM) use in Hong Kong older patients visiting general outpatient clinics (GOPCs) between 2006 and 2014 and to identify factors associated with PIM use among older adults visiting GOPCs in 2014., Design: Cross-sectional study., Setting: GOPC., Participants: Two study samples were constructed including a total of 844 910 patients aged 65 and above from 2006 to 2014 and a cohort of 489 301 older patients in 2014., Measurements: Two subsets of the 2015 American Geriatrics Society Beers criteria-PIMs independent of diagnosis and PIMs due to drug-disease interactions-were used to estimate the prevalence of PIM use over 12 months. PIMs that were not included in the Hospital Authority drug formulary or with any specific restriction or exception in terms of indication, dose or therapy duration were excluded. Characteristics of PIM users and non-PIM users visiting GOPCs in 2014 were compared. Independent associations between patient variables and PIM use were assessed by stepwise multivariable logistic regression analysis., Results: The 12-month period prevalence of PIM use decreased from 55.56% (95% CI 55.39% to 55.72%) in 2006 to 47.51% (95% CI 47.37% to 47.65%) in 2014. In the multivariable regression analysis, the strongest factor associated with PIM use was the number of different drugs prescribed (adjusted OR, AOR 23.01, 95% CI 22.36 to 23.67). Being female (AOR 0.89, 95% CI 0.85 to 0.87 for males vs females) and having a greater number of GOPC visits (AOR 1.83, 95% CI 1.78 to 1.88) as well as more than six diagnoses (AOR 1.43, 95% CI 1.36 to 1.52) were associated with PIM use., Conclusions: The overall prevalence of PIM use in older adults visiting GOPCs decreased from 2006 to 2014 in Hong Kong although the prevalence of PIM use was still high in 2014. Patients with female gender, a larger number of medications prescribed, more frequent visits to GOPCs, and more than six diagnoses were at higher risk for PIM use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by "Cochrane risk of bias 2" tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: - 0.76; 95% CI - 1.19 to - 0.32, I 2  = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections.Protocol registration at PROSPERO: CRD42020214305., (© 2021. The Author(s).)

Studies on vitamin D status and its determinants in growing children in countries with ample sunshine such as Malaysia have been limited. The aim of our study was to determine factors associated with serum 25(OH)D concentrations such as lifestyle, dietary intake, anthropometry, and body composition in 243 pre-adolescent Malaysian children from low-income families living in Kuala Lumpur. This cross-sectional study measured bone density and body composition using dual-energy X-ray absorptiometry (DXA), while serum 25(OH)D was measured using LC-MS/MS. Time spent outdoors, body surface area exposed to sunlight, dietary intake, and physical activity level were assessed using questionnaires. Multiple linear regression and stepwise analysis were performed to identify significant predictors for serum 25(OH)D. About 69.4% had 25(OH)D < 50 nmol/L, and 18.9% were vitamin-D-deficient with 25(OH)D < 30 nmol/L. Girls had a nine-fold higher prevalence of vitamin D deficiency than boys. Body surface area exposed to sunlight, Sun Index, and fat mass were significant predictors of 25(OH)D concentrations in this population. Modifiable lifestyle factors such as sun exposure and reducing obesity are important public health guidance to ensure optimal vitamin D status in these children.

Background: Recruitment and retention in longitudinal nutrition intervention studies among children is challenging and scarcely reported. This paper describes the strategies and lessons learned from a 1-year randomized double-blind placebo-controlled trial among pre-adolescent children on the effects of soluble corn fiber (SCF) on bone indices (PREBONE-Kids)., Methods: Participants (9-11 years old) were recruited and randomized into 4 treatment groups (600 mg calcium, 12 g SCF, 12 g SCF plus 600 mg calcium and placebo). Interventions were consumed as a fruit-flavored powdered drink for 1-year. School-based recruitment was effective due to support on study benefits from parents and teachers, peer influence and a 2-weeks study run-in for participants to assess their readiness to commit to the study protocol. Retention strategies focused on building rapport through school-based fun activities, WhatsApp messaging, providing health screening and travel reimbursements for study measurements. Compliance was enhanced by providing direct on-site school feeding and monthly non-cash rewards. Choice of 2 flavors for the intervention drinks were provided to overcome taste fatigue. Satisfaction level on the manner in which the study was conducted was obtained from a voluntary sub-set of participants., Results: The study successfully enrolled 243 participants within 6 months and retained 82.7% of the participants at the end of 1 year, yielding a drop-out rate of 17.3%. Compliance to the intervention drink was 85% at the start and remained at 78.7% at the end of 1 year. More than 95% of the participants provided good feedback on intervention drinks, rapport building activities, communication and overall study conduct., Conclusion: Successful strategies focused on study benefits, rapport building, frequent communication using social media and non-cash incentives helped improved compliance and retention rate. The lessons learned to maintain a high retention and compliance rate in this study provide valuable insights for future studies in a similar population., Competing Interests: The authors declare there are no conflicts of interest., (© 2021 The Authors.)

The contributions of the viral component of the microbiome-the virome-to the development of innate and adaptive immunity are largely unknown. Here, we systematically defined the host response in mice to a panel of eukaryotic enteric viruses representing six different families. Infections with most of these viruses were asymptomatic in the mice, the magnitude and duration of which was dependent on the microbiota. Flow cytometric and transcriptional profiling of mice mono-associated with these viruses unveiled general adaptations by the host, such as lymphocyte differentiation and IL-22 signatures in the intestine, as well as numerous viral-strain-specific responses that persisted. Comparison with a dataset derived from analogous bacterial mono-association in mice identified bacterial species that evoke an immune response comparable with the viruses we examined. These results expand an understanding of the immune space occupied by the enteric virome and underscore the importance of viral exposure events., Competing Interests: Declaration of interests K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, and Abbvie. K.C. has also consulted for or received an honorarium from Puretech Health, Genentech, and Abbvie. K.C. holds U.S. patent 10,722,600 and provisional patent 62/935,035., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Existing systematic reviews have compared the effectiveness of nurse-led peri-discharge interventions comprising different components with usual care on reducing all-cause 30-day hospital readmissions. However, conflicting results were reported., Objective: We conducted a network meta-analysis to evaluate the comparative effectiveness of different nurse-led peri-discharge interventions, compared with usual care, for reducing all-cause 30-day hospital readmissions., Design: Network meta-analysis., Methods: A total of five international databases were searched for systematic reviews of randomized controlled trials. Additional searches for most updated randomized controlled trials published between 2014 to 2019 were conducted. Data from included randomized controlled trials were extracted for random-effect pairwise meta-analyses. Pooled risk ratios with 95% confidence interval were used to quantify impact of nurse-led peri-discharge interventions on all-cause 30-day hospital readmissions. Network meta-analysis was used to evaluate the comparative effectiveness of different interventions., Results: From two systematic reviews and additional randomized controlled trial searches, 12 eligible randomized controlled trials (n=150,840) assessing 15 different nurse-led peri-discharge interventions were included. For reducing all-cause 30-day hospital readmissions, pairwise meta-analysis showed that there was no significant difference between nurse-led peri-discharge interventions and usual care (pooled risk ratios = 0.86, 95% confidence interval: 0.71-1.04, moderate quality of evidence). Network meta-analysis indicated no significant difference across different interventions despite variation in complexity., Conclusions: Our results indicated that nurse-led peri-discharge interventions were not significantly different from usual care for reducing all-cause 30-day hospital readmissions. Simpler nurse-led peri-discharge interventions are on par with more complex interventions in terms of effectiveness. Benefits of nurse-led peri-discharge interventions may vary across health system context. Therefore, careful consideration is required prior to implementation., Registration Details: The protocol for this study has been registered in PROSPERO (Registration No. CRD42020186938). Tweetable abstract: This study suggested that nurse-led peri-discharge interventions do not differ from usual care for reducing all-cause 30-day hospital readmissions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Ltd.)

Background : During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2-24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants' serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of -6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2-6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E-cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant-mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p < 0.05), after mutual adjustment. The cumulative risk model displayed a dose-response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Background : Standard precautions prevent the spread of infections in healthcare settings. Incompliance with infection control guidelines of healthcare workers (HCWs) may increase their risk of exposure to infectious disease, especially under pandemics. The purpose of this study was to assess the level of compliance with the infection prevention and control practices among HCWs in different healthcare settings and its relationship with their views on workplace infection control measures during the COVID-19 pandemic. Methods : Nurses in Hong Kong were invited to respond to a cross-sectional online survey, in which their views on workplace infection and prevention policy, compliance with standard precautions and self-reported health during pandemics were collected. Results : The respondents were dissatisfied with workplace infection and prevention policy in terms of comprehensiveness (62%), clarity (64%), timeliness (63%), and transparency (60%). For the protective behavior, the respondents did not fully comply with the standard precautions when they were involved in medical care. Their compliance was relatively low when having proper patient handling (54%) and performing invasive procedures (46%). A multivariate analysis model proved that the level of compliance of the standard precautions was positively associated with the satisfaction on infection control and prevention policy among high risk group (0.020; 95% CI: 0.005-0.036), while older respondents had higher level of compliance among the inpatient and outpatient groups (coefficient range: 0.065-0.076). The higher level of compliance was also significantly associated with working in designated team and having chronic condition of the respondents among high-risk and inpatient groups. Conclusions : Standard precautions are the most important elements to reduce cross-transmission among HCWs and patients while the satisfaction on infection control and prevention policy would increase the compliance among the high-risk group. An overall suboptimal compliance and poor views on the infection prevention and control guidelines is a warning signal to healthcare system especially during pandemics.

Background: Given the public health responses to previous respiratory disease pandemics, and in the absence of treatments and vaccines, the mitigation of the COVID-19 pandemic relies on population engagement in nonpharmaceutical interventions. This engagement is largely driven by risk perception, anxiety levels, and knowledge, as well as by historical exposure to disease outbreaks, government responses, and cultural factors., Objective: The aim of this study is to compare psychobehavioral responses in Hong Kong and the United Kingdom during the early phase of the COVID-19 pandemic., Methods: Comparable cross-sectional surveys were administered to adults in Hong Kong and the United Kingdom during the early phase of the epidemic in each setting. Explanatory variables included demographics, risk perception, knowledge of COVID-19, anxiety level, and preventive behaviors. Responses were weighted according to census data. Logistic regression models, including effect modification to quantify setting differences, were used to assess the association between the explanatory variables and the adoption of social distancing measures., Results: Data from 3431 complete responses (Hong Kong, 1663; United Kingdom, 1768) were analyzed. Perceived severity of symptoms differed by setting, with weighted percentages of 96.8% for Hong Kong (1621/1663) and 19.9% for the United Kingdom (366/1768). A large proportion of respondents were abnormally or borderline anxious (Hong Kong: 1077/1603, 60.0%; United Kingdom: 812/1768, 46.5%) and regarded direct contact with infected individuals as the transmission route of COVID-19 (Hong Kong: 94.0%-98.5%; United Kingdom: 69.2%-93.5%; all percentages weighted), with Hong Kong identifying additional routes. Hong Kong reported high levels of adoption of various social distancing measures (Hong Kong: 32.6%-93.7%; United Kingdom: 17.6%-59.0%) and mask-wearing (Hong Kong: 98.8% (1647/1663); United Kingdom: 3.1% (53/1768)). The impact of perceived severity of symptoms and perceived ease of transmission of COVID-19 on the adoption of social distancing measures varied by setting. In Hong Kong, these factors had no impact, whereas in the United Kingdom, those who perceived their symptom severity as "high" were more likely to adopt social distancing (adjusted odds ratios [aORs] 1.58-3.01), and those who perceived transmission as "easy" were prone to adopt both general social distancing (aOR 2.00, 95% CI 1.57-2.55) and contact avoidance (aOR 1.80, 95% CI 1.41-2.30). The impact of anxiety on adopting social distancing did not vary by setting., Conclusions: Our results suggest that health officials should ascertain baseline levels of risk perception and knowledge in populations, as well as prior sensitization to infectious disease outbreaks, during the development of mitigation strategies. Risk should be communicated through suitable media channels-and trust should be maintained-while early intervention remains the cornerstone of effective outbreak response., (©Leigh Bowman, Kin On Kwok, Rozlyn Redd, Yuanyuan Yi, Helen Ward, Wan In Wei, Christina Atchison, Samuel Yeung-Shan Wong. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.03.2021.)

The effectiveness of seasonal influenza vaccines varies with the matching of vaccine strains to circulating strains. Based on the genetic distance of hemagglutinin and neuraminidase gene of the influenza viruses to vaccine strains, we statistically quantified the relationship between the genetic mismatch and vaccine effectiveness (VE) for influenza A/H1N1pdm09, A/H3N2 and B. We also proposed a systematic approach to integrate multiple genes and influenza types for overall VE estimation. Evident linear relationships were identified and validated in independent data. The modelling framework may enable in silico prediction for VE on a real-time basis and inform the influenza vaccine selection strategy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [M.H.W and B.C.Y.Z are shareholders of Beth Bioinformatics Co., Ltd. B.C.Y.Z is a shareholder of Health View Bioanalytics Ltd. All other authors declare no competing interests.]., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The novel coronavirus (COVID-19) infection has spread worldwide since late 2019. People who have social contacts with COVID-19 patients might be at higher risk of physical or mental health problems. This study investigated whether people who had social contacts with COVID-19 patients would have poorer physical or mental outcomes, and different attitudes and behaviors. Chinese adults were recruited to fill in an online survey using snowball sampling during 21st-26nd February 2020. Physical symptoms, psychological outcomes, quality of life, COVID-19 related attitudes, and behaviors were measured. The differences in the outcomes between participants who had COVID-19 social contacts and those who had not were analyzed. The survey included 1,447 non-infected eligible participants. Among those, 173 (12.0%) reported at least one confirmed/suspected case in their social contacts. In the multiple regression adjusted for demographic data, the presence of confirmed/suspected infection cases in one's social contacts was significantly associated with poorer physical and mental outcomes, lower health-related quality of life, and different COVID-19 related attitudes and behaviors (p<0.05). In conclusion, people who had social contacts with COVID-19 patients were at risk of adverse health outcomes. Future studies are needed to understand the long-term impacts. Similarly, strategies to improve health outcomes for these people are needed., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous clinical trials have demonstrated that both acupuncture and sham acupuncture exert significant, non-specific effects on treatment outcomes when compared to no-treatment controls. A recently developed framework (mechanisms in orthodox and complementary and alternative medicine-MOCAM) suggests that the non-specific effects of acupuncture originate from multiple domains (e.g. patient characteristics, acupuncturist skill/technique, the patient-acupuncturist relationship, and the acupuncture environment). However, it remains to be determined precisely how these domains influence the non-specific effects of treatment among patients receiving acupuncture and sham acupuncture in clinical trials. Therefore, we conducted a systematic review to synthesize existing qualitative evidence on how trial participants randomized to acupuncture and sham acupuncture groups experience non-specific effects, regardless of the types of medical condition investigated., Methods: This systematic review included primary qualitative studies embedded in randomized controlled trials designed to investigate acupuncture or sham acupuncture interventions. Eligible studies published in English were derived from a search of five international databases. The methodological quality of included studies was evaluated using the Critical Appraisal Skills Programme (CASP) tool. Using a framework synthesis approach, the identified MOCAM framework was adapted based on the synthesis of the available qualitative evidence., Results: A total of 20 studies of high methodological quality were included. Our proposed model indicated that the effects of acupuncture may be increased by maintaining a professional status, applying a holistic treatment approach, practicing empathy, and providing patients with an appropriate explanation of the theory behind acupuncture and sham acupuncture. From the patient's perspective, the efficacy of treatment can be increased by following the lifestyle modification advice provided by acupuncturists, maintaining a positive attitude toward treatment efficacy, actively engaging with acupuncturists during consultation, and making behavioral changes based on experience gained during the trial., Conclusion: The results of this study may provide a basis for improving and standardizing key components of non-specific effects in acupuncture treatment, and for improving the isolation of specific effects in future clinical trials involving acupuncture and sham acupuncture.

Hypothalamic inflammation has been linked to various aspects of central metabolic dysfunction and diseases in humans, including hyperphagia, altered energy expenditure, and obesity. We previously reported that loss of β-carotene oxygenase 2 (BCO2), a mitochondrial inner membrane protein, causes the alteration of the hypothalamic metabolome, low-grade inflammation, and an increase in food intake in mice at an early age, e.g., 3-6 weeks. Here, we determined the extent to which the deficiency of BCO2 induces hypothalamic inflammation in BCO2 knockout mice. Mitochondrial proteomics, electron microscopy, and immunoblotting were used to assess the changes in hypothalamic mitochondrial dynamics and mitochondrial DNA sensing and signaling. The results showed that deficiency of BCO2 altered hypothalamic mitochondrial proteome and respiratory supercomplex assembly by enhancing the expression of NADH:ubiquinone oxidoreductase subunit A11 protein and improved cardiolipin synthesis. BCO2 deficiency potentiated mitochondrial fission but suppressed mitophagy and mitochondrial biogenesis. Furthermore, deficiency of BCO2 resulted in inactivation of mitochondrial MnSOD enzyme, excessive production of reactive oxygen species, and elevation of protein levels of stimulator of interferon genes (STING) and interferon regulatory factor 3 (IRF3) in the hypothalamus. The data suggest that BCO2 is essential for hypothalamic mitochondrial dynamics. BCO2 deficiency induces mitochondrial fragmentation and mitochondrial oxidative stress, which may lead to mitochondrial DNA release into the cytosol and subsequently sensing by activation of the STING-IRF3 signaling pathway in the mouse hypothalamus., Competing Interests: Declaration of Competing Interest No competing interests declared., (Copyright © 2020. Published by Elsevier Inc.)

The mechanism of the magnetic compass sense of migratory songbirds is thought to involve magnetically sensitive chemical reactions of light-induced radical pairs in cryptochrome proteins located in the birds' eyes. However, it is not yet clear whether this mechanism would be sensitive enough to form the basis of a viable compass. In the present work, we report spin dynamics simulations of models of cryptochrome-based radical pairs to assess whether accumulation of nuclear spin polarization in multiple photocycles could lead to significant enhancements in the sensitivity with which the proteins respond to the direction of the geomagnetic field. Although buildup of nuclear polarization appears to offer sensitivity advantages in the more idealized model systems studied, we find that these enhancements do not carry over to conditions that more closely resemble the situation thought to exist in vivo. On the basis of these simulations, we conclude that buildup of nuclear polarization seems unlikely to be a source of significant improvements in the performance of cryptochrome-based radical pair magnetoreceptors.

Vaccine hesitancy is among the major threats to the effectiveness of vaccination programmes. This study aimed to report the trend in response to willingness to accept the COVID-19 vaccine between two waves of the local epidemic and examine differences among occupations. Two cross-sectional surveys were conducted online during the first wave (February) and third wave (August to September) of the local epidemic in 2020. Acceptance of the COVID-19 vaccine was measured along with personal protection behaviours and occupations. A total of 2047 participants provided valid responses. The willingness to accept the COVID-19 vaccine among the participants was lower in the third wave (34.8%) than the first wave (44.2%). There were more concerns over vaccine safety in the third wave. Clerical/service/sales workers were less likely to accept the vaccine (adjusted odds ratio: 0.62, 95% confidence interval: 0.43-0.91). A high-level compliance of facemask wearing was found, and more people maintained social distancing and used alcohol hand rub in the third wave. Decreasing willingness to accept the COVID-19 vaccine may be associated with increasing concerns about vaccine safety and growing compliance of personal protection behaviours. The rush of vaccine development with higher risks of safety issues may jeopardize the public's trust and lower uptake rates. Education and favourable policy should be provided to the general working population for the vaccination, especially for those who are not professional and are frequently exposed to crowds.

Purpose of Review: Automated office blood pressure (AOBP) measurements may provide more accurate estimation of blood pressure (BP) than manual office blood pressure (MOBP) measurements. This systematic review investigated the diagnostic performance of AOBP and MOBP using ambulatory blood pressure measurement (ABPM) as reference. Several databases including MEDLINE, Embase, Scopus, and China Academic Journals were searched. Data were extracted, double-checked by two investigators, and were analysed using a random effects model., Recent Findings: A total of 26 observational studies were included. The mean systolic/diastolic BP obtained by AOBP was not significantly different from that obtained by ABPM. The sensitivity and specificity of AOBP to detect elevated BP were approximately 70%. Fewer participants had white-coat hypertension on AOBP measurement than on MOBP measurement (7% versus 14%); however, about 13% had masked hypertension on AOBP measurement. The width of the limit of agreement comparing (i) AOBP and ABPM and (ii) MOBP and ABPM was comparable. AOBP may reduce the rate of the observed white-coat effect but undermine masked hypertension. The current recommendation, however, is limited by the absence of high-quality studies and the high heterogeneity of our results. More high-quality studies using different AOBP machines and in different population are therefore needed.

Cardiovascular diseases (CVDs) are the leading cause of death today. The current identification method of the diseases is analyzing the Electrocardiogram (ECG), which is a medical monitoring technology recording cardiac activity. Unfortunately, looking for experts to analyze a large amount of ECG data consumes too many medical resources. Therefore, the method of identifying ECG characteristics based on machine learning has gradually become prevalent. However, there are some drawbacks to these typical methods, requiring manual feature recognition, complex models, and long training time. This paper proposes a robust and efficient 12-layer deep one-dimensional convolutional neural network on classifying the five micro-classes of heartbeat types in the MIT- BIH Arrhythmia database. The five types of heartbeat features are classified, and wavelet self-adaptive threshold denoising method is used in the experiments. Compared with BP neural network, random forest, and other CNN networks, the results show that the model proposed in this paper has better performance in accuracy, sensitivity, robustness, and anti-noise capability. Its accurate classification effectively saves medical resources, which has a positive effect on clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Lu, Yang and Wong.)

The replacement of small-diameter arteries remains an unmet clinical need. Here we investigated the cellular remodeling of fibrotic conduits as vascular grafts. The formation of fibrotic conduit around subcutaneously implanted mandrels involved not only fibroblasts but also the trans-differentiation of inflammatory cells such as macrophages into fibroblastic cells, as shown by genetic lineage tracing. When fibrotic conduits were implanted as vascular grafts, the patency was low, and many fibrotic cells were found in neointima. Decellularization and anti-thrombogenic coating of fibrotic conduits produced highly patent autografts that remodeled into neoarteries, offering an effective approach to obtain autografts for clinical therapy. While autografts recruited mostly anti-inflammatory macrophages for constructive remodeling, allogenic DFCs had more T cells and pro-inflammatory macrophages and lower patency. Endothelial progenitors and endothelial migration were observed during endothelialization. Cell infiltration into DFCs was more efficient than decellularized arteries, and infiltrated cells remodeled the matrix and differentiated into smooth muscle cells (SMCs). This work provides insight into the remodeling of fibrotic conduits, autologous DFCs and allogenic DFCs, and will have broad impact on using fibrotic matrix for regenerative engineering., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aims: Meta-analysis shows that up to 26% of adenomas could be missed during colonoscopy. We investigated whether the use of artificial intelligence (AI)-assisted real-time detection could provide new insights into mechanisms underlying missed lesions during colonoscopy., Methods: A validated real-time deep-learning AI model for the detection of colonic polyps was first tested in videos of tandem colonoscopy of the proximal colon for missed lesions. The real-time AI model was then prospectively validated in a total colonoscopy in which the endoscopist was blinded to real-time AI findings. Segmental unblinding of the AI findings were provided, and the colonic segment was then re-examined when missed lesions were detected by AI but not the endoscopist. All polyps were removed for histologic examination as the criterion standard., Results: Sixty-five videos of tandem examination of the proximal colon were reviewed by AI. AI detected 79.1% (19/24) of missed proximal adenomas in the video of the first-pass examination. In 52 prospective colonoscopies, real-time AI detection detected at least 1 missed adenoma in 14 patients (26.9%) and increased the total number of adenomas detected by 23.6%. Multivariable analysis showed that a missed adenoma(s) was more likely when there were multiple polyps (adjusted odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P < .0001) or colonoscopy was performed by less-experienced endoscopists (adjusted odds ratio, 1.30; 95% confidence interval, 1.05-1.62; P = .02)., Conclusions: Our findings provide new insights on the prominent role of human factors, including inexperience and distraction, on missed colonic lesions. With the use of real-time AI assistance, up to 80% of missed adenomas could be prevented. (Clinical trial registration number: NCT04227795.)., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: As the coronavirus disease 2019 (COVID-19) pandemic is sweeping across the globe, there is an urgent need to develop effective vaccines as the most powerful strategy to end the pandemic. This study aimed to examine how factors related to vaccine characteristics, their social normative influence and convenience of vaccination can affect the public's preference for the uptake of the COVID-19 vaccine in China., Methods: An online discrete choice experiment (DCE) survey was administered to a sample of China's general population. Participants were asked to make a series of hypothetical choices and estimate their preference for different attributes of the vaccine. A mixed logit regression model was used to analyse the DCE data. Willingness to pay for each attribute was also calculated., Results: Data of 1236 participants who provided valid responses were included in the analysis. There was strong public preference for high effectiveness of the vaccine, followed by long protective duration, very few adverse events and being manufactured overseas. Price was the least important attribute affecting the public preference in selecting the COVID-19 vaccine., Conclusions: The strong public preferences detected in this study should be considered when developing COVID-19 vaccination programme in China. The results provide useful information for policymakers to identify the individual and social values for a good vaccination strategy., Patient or Public Contribution: The design of the experimental choices was fully based on interviews and focus group discussions participated by 26 Chinese people with diverse socio-economic backgrounds. Without their participation, the study would not be possible., (© 2020 The Authors Health Expectations published by John Wiley & Sons Ltd.)

Objectives: Globally, the COVID-19 pandemic has overwhelmed many healthcare systems, which has hampered access to routine clinical care during lockdowns. Informal home care, care provided by non-healthcare professionals, increases the community's healthcare capacity during pandemics. There is, however, limited research about the characteristics of informal home care providers and the challenges they face during such public health emergencies., Design: A random, cross-sectional, population-based, RDD, telephone survey study was conducted to examine patterns of home care, characteristics of informal home care providers and the challenges experienced by these care providers during this pandemic., Setting: Data were collected from 22 March to 1 April 2020 in Hong Kong, China., Participants: A population representative study sample of Chinese-speaking adults (n=765) was interviewed., Primary and Secondary Outcome Measures: The study examined the characteristics of informal home care providers and self-reported health requirements of those who needed care. The study also examined providers' self-perceived knowledge to provide routine home care as well as COVID-19 risk reduction care. Respondents were asked of their mental health status related to COVID-19., Results: Of the respondents, 25.1% of 765 provided informal home care during the studied COVID-19 pandemic period. Among the informal home care providers, 18.4% of respondents took leave from school/work during the epidemic to provide care for the sick, fragile elderly and small children. Care providers tended to be younger aged, female and housewives. Approximately half of care providers reported additional mental strain and 37.2% reported of challenges in daily living during epidemic. Although most informal home care providers felt competent to provide routine care, 49.5% felt inadequately prepared to cope with the additional health risks of COVID-19., Conclusion: During public health emergencies, heavy reliance on informal home healthcare providers necessitates better understanding of their specific needs and increased government services to support informal home care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: A systematic review on the reproducibility of ambulatory blood pressure measurements (ABPM) has not yet been conducted. This meta-analysis compared 24-h/daytime/night-time SBP and DBP mean values and SBP/DBP nocturnal dipping status from ABPMs in participants with or without hypertension., Methods: Ovid MEDLINE, EMBASE, and CINAHL Complete databases were searched for articles published before 3 May 2019. Eligible studies reporting a 24-h ABPM repeated at least once within 1 month were included. The mean daytime/night-time/24-h BP values, percentage of nocturnal dipping, and proportion of nondippers were compared between the first and second day of measurements, and the proportion of participants with inconsistent dipping status were estimated using a random effect model., Results: Population-based analysis found a 0-1.1 mmHg difference between the first and second ABPM for 24-h/daytime/night-time SBP and DBP and 0-0.5% for percentage of SBP/DBP nocturnal dipping. The proportion of non-dippers was not different between the first and second ABPM. Intra-individual analysis found that the 95% limit of agreements (LOA) for SBP/DBP were wide and the 95% LOA for daytime SBP, common reference to diagnose hypertension, ranged -16.7 to 18.4 mmHg. Similarly, 32% of participants had inconsistent nocturnal dipping status., Conclusion: ABPM had excellent reproducibility at the population level, favouring its application for research purposes; but reproducibility of intra-individual BP values and dipping status from a 24-h ABPM was limited. The available evidence was limited by the lack of high-quality studies and lack of studies in non-Western populations.

Objectives: The recruitment and adherence status of randomized controlled trials (RCTs) for population with mild cognitive impairment (MCI) are little known. We aimed to explore the RCT recruitment and adherence status and factors associated with these among MCI patients., Methods: We searched MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO, and PsycARTICLES from inception to 8th July 2019. Included studies were RCTs conducted among MCI patients with available data of invitation rate, eligibility rate, randomization rate, recruitment rate, adherence rate, satisfaction rate, or potential barrier for recruitment and compliance. Two authors screened the studies and extracted the data independently. We calculated pooled proportions of each rate and their 95% confidence intervals (CIs) using random-effects meta-analysis. Meta-regression and subgroup analysis was conducted., Results: Hundred and ten articles were judged to meet the study inclusion criteria from 10 387 articles. The invitation rates ranged from 9% to96% but were not pooled together due to high heterogeneity. The pooled overall eligibility, randomization, recruitment, intervention adherence, and follow-up adherence rates were 55% (95% CI: 48%-62%), 86% (95% CI: 81%-91%), 44% (95% CI: 37%-50%), 88% (95% CI: 86%-90%), and 85% (95% CI: 83%-87%), respectively. Non-MCI (47.5%), disease or medical problems (13.8%), and loss of interest (8.5%) were the most frequent reasons for screen failure. Refusal without reason (36.6%), adverse events (30.9%), and health issues (7.7%) were the most frequent reasons for drop-out., Conclusions: This study provided important information for future RCTs targeting at MCI patients. Strategies designed to improve participant recruitment and RCT adherence should be developed among this population., (© 2020 John Wiley & Sons Ltd.)

Introduction: Little is known about the relationship of whole-grain intake with dietary fatty acids intake. The present study aimed to assess the whole-grain intake and its relationships with dietary fatty acids intake among multiethnic schoolchildren in Kuala Lumpur, Malaysia., Methods: This cross-sectional study was conducted among 392 schoolchildren aged 9-11 years, cluster sampled from five randomly selected schools in Kuala Lumpur. Whole-grain and fatty acids intakes were assessed by 3-day, 24-h diet recalls. All whole-grain foods were considered irrespective of the amount of whole grain they contained., Results: In total, 55.6% (n = 218) were whole-grain consumers. Mean (SD) daily intake of whole grain in the total sample was 5.13 (9.75) g day -1 . In the whole-grain consumer's only sample, mean (SD) intakes reached 9.23 (11.55) g day -1 . Significant inverse associations were found between whole-grain intake and saturated fatty acid (SAFA) intake (r = -0.357; P < 0.001), monosaturated fatty acid (MUFA) (r = -0.373; P < 0.001) and polyunsaturated fatty acid (PUFA) (r = -0.307; P < 0.001) intake. Furthermore, whole-grain intake was a significant predictor of SAFA (β = -0.077; P = 0.004), MUFA (β = -0.112; P = <0.001) and PUFA (β = -0.202; P = <0.001) intakes, after controlling for sex, age and ethnicity., Conclusions: Whole-grain intake in Malaysia was well below recommendations. Schoolchildren who consumed higher whole grain tend to reduce fat intake; however, it would also reduce the SAFA, MUFA and PUFA intakes. Future collaboration may be conducted between industry, government and universities to promote unsaturated fatty acids-rich foods and whole-grain food, although not to promote processed whole-grain foods with a high sugar and salt content., (© 2020 The British Dietetic Association Ltd.)

Background: Gestational diabetes mellitus (GDM) can cause adverse consequences to both mothers and their newborns. However, pregnant women living in low- and middle-income areas or countries often fail to receive early clinical interventions at local medical facilities due to restricted availability of GDM diagnosis. The outstanding performance of artificial intelligence (AI) in disease diagnosis in previous studies demonstrates its promising applications in GDM diagnosis., Objective: This study aims to investigate the implementation of a well-performing AI algorithm in GDM diagnosis in a setting, which requires fewer medical equipment and staff and to establish an app based on the AI algorithm. This study also explores possible progress if our app is widely used., Methods: An AI model that included 9 algorithms was trained on 12,304 pregnant outpatients with their consent who received a test for GDM in the obstetrics and gynecology department of the First Affiliated Hospital of Jinan University, a local hospital in South China, between November 2010 and October 2017. GDM was diagnosed according to American Diabetes Association (ADA) 2011 diagnostic criteria. Age and fasting blood glucose were chosen as critical parameters. For validation, we performed k-fold cross-validation (k=5) for the internal dataset and an external validation dataset that included 1655 cases from the Prince of Wales Hospital, the affiliated teaching hospital of the Chinese University of Hong Kong, a non-local hospital. Accuracy, sensitivity, and other criteria were calculated for each algorithm., Results: The areas under the receiver operating characteristic curve (AUROC) of external validation dataset for support vector machine (SVM), random forest, AdaBoost, k-nearest neighbors (kNN), naive Bayes (NB), decision tree, logistic regression (LR), eXtreme gradient boosting (XGBoost), and gradient boosting decision tree (GBDT) were 0.780, 0.657, 0.736, 0.669, 0.774, 0.614, 0.769, 0.742, and 0.757, respectively. SVM also retained high performance in other criteria. The specificity for SVM retained 100% in the external validation set with an accuracy of 88.7%., Conclusions: Our prospective and multicenter study is the first clinical study that supports the GDM diagnosis for pregnant women in resource-limited areas, using only fasting blood glucose value, patients' age, and a smartphone connected to the internet. Our study proved that SVM can achieve accurate diagnosis with less operation cost and higher efficacy. Our study (referred to as GDM-AI study, ie, the study of AI-based diagnosis of GDM) also shows our app has a promising future in improving the quality of maternal health for pregnant women, precision medicine, and long-distance medical care. We recommend future work should expand the dataset scope and replicate the process to validate the performance of the AI algorithms., (©Jiayi Shen, Jiebin Chen, Zequan Zheng, Jiabin Zheng, Zherui Liu, Jian Song, Sum Yi Wong, Xiaoling Wang, Mengqi Huang, Po-Han Fang, Bangsheng Jiang, Winghei Tsang, Zonglin He, Taoran Liu, Babatunde Akinwunmi, Chi Chiu Wang, Casper J P Zhang, Jian Huang, Wai-Kit Ming. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.09.2020.)

Phosphoglucomutase 1 deficiency is a congenital disorder of glycosylation (CDG) with multiorgan involvement affecting carbohydrate metabolism, N-glycosylation and energy production. The metabolic management consists of dietary D-galactose supplementation that ameliorates hypoglycemia, hepatic dysfunction, endocrine anomalies and growth delay. Previous studies suggest that D-galactose administration in juvenile patients leads to more significant and long-lasting effects, stressing the urge of neonatal diagnosis (0-6 months of age). Here, we detail the early clinical presentation of PGM1-CDG in eleven infantile patients, and applied the modified Beutler test for screening of PGM1-CDG in neonatal dried blood spots (DBSs). All eleven infants presented episodic hypoglycemia and elevated transaminases, along with cleft palate and growth delay (10/11), muscle involvement (8/11), neurologic involvement (5/11), cardiac defects (2/11). Standard dietary measures for suspected lactose intolerance in four patients prior to diagnosis led to worsening of hypoglycemia, hepatic failure and recurrent diarrhea, which resolved upon D-galactose supplementation. To investigate possible differences in early vs. late clinical presentation, we performed the first systematic literature review for PGM1-CDG, which highlighted respiratory and gastrointestinal symptoms as significantly more diagnosed in neonatal age. The modified Butler-test successfully identified PGM1-CDG in DBSs from seven patients, including for the first time Guthrie cards from newborn screening, confirming the possibility of future inclusion of PGM1-CDG in neonatal screening programs. In conclusion, severe infantile morbidity of PGM1-CDG due to delayed diagnosis could be prevented by raising awareness on its early presentation and by inclusion in newborn screening programs, enabling early treatments and galactose-based metabolic management., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe how a pediatric postanesthesia care unit used a two-phased approach of bundled interventions to reduce unit noise levels and improve staff perceptions of their work environment., Design: Pre/post design., Methods: Postanesthesia care unit sound levels and monitor alarms were measured at baseline and after implementing both project phases. Nursing staff members were surveyed at baseline and after completion of the project., Findings: Monitor alarms were reduced by more than 50% after Phase I. However, noise measurement data did not reflect a difference in sound levels between baseline and intervention phases. Despite this, staff perceived the unit as much quieter., Conclusions: The reduction in monitor alarms did not cause an appreciable change in sound levels as measured by noise dosimeters in either intervention phase. Despite these findings, nurses perceived a quieter and more pleasant workplace. These impressions might have resulted from subjective expectations versus actual volume levels, or they might owe to the reduction in incidence of alarms themselves, which they had viewed as nuisance sounds., (Copyright © 2020 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: In response to population aging, there is a need for health systems to focus on care for chronic disease, specifically palliative care, while focusing on people-centered care. The objective of this study is to explore the healthcare system enablers and barriers to the provision of quality palliative and end-of-life care from the perspective of healthcare professionals., Materials and Methods: Using purposive sampling, fifteen focus group interviews and nine individual interviews involving 72 healthcare providers were conducted. Primary qualitative data were collected between May 2016 and July 2017. All recorded discussions were transcribed verbatim and analyzed. A thematic framework was developed., Results: The provision of quality palliative and end-of-life care is influenced by the interaction and integration of nine sub-themes under four identified themes: (1) political context; (2) organization setting; (3) support to patients, caregivers, and family members, and (4) healthcare workers and the public., Conclusions: Integration of palliative and end-of-life care is an important pillar of healthcare service to improve quality of life by addressing patients' values, wishes and preference, and assist their family to handle challenges at the end stage of life. Further improvements to the service framework would be required, specifically in the political framework, multidisciplinary approach, and readiness and competence in healthcare workers and community. These were highlighted in our study as key components in service provision to ensure that patients can receive continuous and integrated care between hospitals and the community as well as dignified care at the end stage of life.

The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID-19) are still emerging. Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic. At present, there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID-19 pandemic., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Resident soil microbiota play key roles in sustaining the core ecosystem processes of terrestrial Antarctica, often involving unique taxa with novel functional traits. However, the full scope of biodiversity and the niche-neutral processes underlying these communities remain unclear. In this study, we combine multivariate analyses, co-occurrence networks and fitted species abundance distributions on an extensive set of bacterial, micro-eukaryote and archaeal amplicon sequencing data to unravel soil microbiome patterns of nine sites across two east Antarctic regions, the Vestfold Hills and Windmill Islands. To our knowledge, this is the first microbial biodiversity report on the hyperarid Vestfold Hills soil environment., Results: Our findings reveal distinct regional differences in phylogenetic composition, abundance and richness amongst microbial taxa. Actinobacteria dominated soils in both regions, yet Bacteroidetes were more abundant in the Vestfold Hills compared to the Windmill Islands, which contained a high abundance of novel phyla. However, intra-region comparisons demonstrate greater homogeneity of soil microbial communities and measured environmental parameters between sites at the Vestfold Hills. Community richness is largely driven by a variable suite of parameters but robust associations between co-existing members highlight potential interactions and sharing of niche space by diverse taxa from all three microbial domains of life examined. Overall, non-neutral processes appear to structure the polar soil microbiomes studied here, with niche partitioning being particularly strong for bacterial communities at the Windmill Islands. Eukaryotic and archaeal communities reveal weaker niche-driven signatures accompanied by multimodality, suggesting the emergence of neutrality., Conclusion: We provide new information on assemblage patterns, environmental drivers and non-random occurrences for Antarctic soil microbiomes, particularly the Vestfold Hills, where basic diversity, ecology and life history strategies of resident microbiota are largely unknown. Greater understanding of these basic ecological concepts is a pivotal step towards effective conservation management.

Objective: To assess the effect of peer-identified change agents (PICAs) compared to management-selected change agents (MSCAs) on hand hygiene behavior in acute care., Design: Randomized-controlled study., Setting: Two internal medicine wards of a public, university-affiliated, tertiary-care hospital in Malaysia., Methods: We randomly allocated 2 wards to hand hygiene promotion delivered either by PICAs (study arm 1) or by MSCAs (study arm 2). The primary outcome was hand hygiene compliance using direct observation by validated auditors. Secondary outcomes were hand hygiene knowledge and observations from ward tours., Results: Mean hand hygiene compliance in study arm 1 and study arm 2 improved from 48% (95% confidence interval [CI], 44%-53%) and 50% (95% CI, 44%-55%) in the preintervention period to 66% (63%-69%) and 65% (60%-69%) in the intervention period, respectively. We detected no statistically significant difference in hand hygiene improvement between the 2 study arms. Knowledge scores on hand hygiene in study arm 1 and study arm 2 improved from 60% and 63% to 98% and 93%, respectively. Staff in study arm 1 improved hand hygiene because they did not want to disappoint the efforts taken by the PICAs. Staff in study arm 2 felt pressured by the MSCAs to comply with hand hygiene to obtain good overall performance appraisals., Conclusion: Although the attitude of PICAs and MSCAs in terms of leadership, mode of action and perception of their task by staff were very different, or even opposed, both PICAs and MSCAs effectively changed behavior of staff toward improved hand hygiene to comparable levels.

Background: We examined the association of housing affordability with physical and mental health in Hong Kong, where there is a lack of related research despite having the worst housing affordability problem in the world, considering potential mediating effect of deprivation., Methods: A stratified random sample of 1978 Hong Kong adults were surveyed. Housing affordability was defined using the residual-income (after housing costs) approach. Health-related quality of life was assessed by the Short-Form Health Survey version 2 (SF-12v2), from which the physical component summary (PCS) and mental component summary (MCS) measures were derived. Multivariable linear regressions were performed to assess associations of housing affordability with PCS and MCS scores, adjusting for sociodemographic, socioeconomic and lifestyle factors. Mediation analyses were also conducted to assess the mediating role of deprivation on the effect of housing affordability on PCS or MCS., Results: Dose-response relationships were observed between housing affordability and mean PCS score ( β (95% CI) compared with the highest affordable fourth quartile: -2.53 (-4.05 to -1.01), -2.23 (-3.54 to -0.92), -0.64 (-1.80 to 0.51) for the first, second and third quartiles, respectively) and mean MCS score ( β (95% CI): -3.87 (-5.30 to -2.45), -2.35 (-3.59 to -1.11), -1.28 (-2.40 to -0.17) for the first, second and third quartiles, respectively). Deprivation mediated 34.3% of the impact of housing unaffordability on PCS and 15.8% of that on MCS., Conclusions: Housing affordability affects physical and mental health, partially through deprivation, suggesting that housing policies targeting deprived individuals may help reduce health inequality in addition to targeting the housing affordability problem., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Poverty and ill-health are closely inter-related. Existing studies on the poverty-health vicious cycle focus mainly on less developed countries, where the identified mechanisms linking between poverty and ill-health may not fit the situations in developed Asian regions. This study aims to qualitatively explore the perceived mechanisms and drivers of the poverty-health vicious cycle among major stakeholders in the healthcare setting in Hong Kong., Methods: Data were collected via focus group interviews with social workers (n = 8), chronically ill patients (n = 8), older adults (n = 6), primary care doctors (n = 7) and informal caregivers (n = 10). The transcribed data were then closely read to capture key themes using thematic analyses informed by social constructivism., Results: In this highly developed Asian setting with income inequality among the greatest in the world, the poverty-health vicious cycle operates. Material and social constraints, as a result of unequal power and opportunities, appear to play a pivotal role in creating uneven distribution of social determinants of health. The subsequent healthcare access also varies across the social ladder under the dual-track healthcare system in Hong Kong. As health deteriorates, financial hardship is often resulted in the absence of sufficient and coordinated healthcare, welfare and labour policy interventions. In addition to the mechanisms, policy drivers of the cycle were also discussed based on the respondents' perceived understanding of the nature of poverty and its operationalization in public policies, as well as of the digressive conceptions of disease among different stakeholders., Conclusions: The poverty-health vicious cycle has remained a great challenge in Hong Kong despite its economic prosperity. To break the cycle, potential policy directions include the adoption of proportionate universalism, social integration and the strengthening of medical-social collaboration.

Background and Aims: Linked color imaging (LCI) is a newly available image-enhanced endoscopy (IEE) system that emphasizes the red mucosal color. No study has yet compared LCI with other available IEE systems. Our aim was to investigate polyp detection rates using LCI compared with narrow-band imaging (NBI)., Methods: This is a prospective randomized tandem colonoscopy study. Eligible patients who underwent colonoscopy for symptoms or screening/surveillance were randomized in a 1:1 ratio to receive tandem colonoscopy with both colonoscope withdrawals using LCI or NBI. The primary outcome was the polyp detection rate., Results: Two hundred seventy-two patients were randomized (mean age, 62 years; 48.2% male; colonoscopy for symptoms, 72.8%) with 136 in each arm. During the first colonoscopy, the polyp detection rate (71.3% vs 55.9%; P = .008), serrated lesion detection rate (34.6% vs 22.1%; P = .02), and mean number of polyps detected (2.04 vs 1.35; P = .02) were significantly higher in the NBI group than in the LCI group. There was also a trend of higher adenoma detection rate in the NBI group compared with the LCI group (51.5% vs 39.7%, respectively; P = .05). Multivariable analysis confirmed that use of NBI (adjusted odds ratio, 1.99; 95% confidence interval, 1.09-3.68) and withdrawal time >8 minutes (adjusted odds ratio, 5.11; 95% confidence interval, 2.79-9.67) were associated with polyp detection. Overall, 20.5% of polyps and 18.1% of adenomas were missed by the first colonoscopy, but there was no significant difference in the miss rates between the 2 groups., Conclusion: NBI was significantly better than LCI for colorectal polyp detection. However, both LCI and NBI missed 20.5% of polyps. (Clinical trial registration number: NCT03336359.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Ischemic heart disease represents the leading cause of death worldwide. Heart failure following myocardial infarction (MI) is associated with severe fibrosis formation and cardiac remodeling. Recently, injectable hydrogels have emerged as a promising approach to repair the infarcted heart and improve heart function through minimally invasive administration. Here, a novel injectable human amniotic membrane (hAM) matrix is developed to enhance cardiac regeneration following MI. Human amniotic membrane is isolated from human placenta and engineered to be a thermoresponsive, injectable gel around body temperature. Ultrasound-guided injection of hAM matrix into rat MI hearts significantly improves cardiac contractility, as measured by ejection fraction (EF), and decrease fibrosis. The results of this study demonstrate the feasibility of engineering as an injectable hAM matrix and its efficacy in attenuating degenerative changes in cardiac function following MI, which may have broad applications in tissue regeneration., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The poor prognosis of glioblastoma (GBM) is associated with a highly invasive stem-like subpopulation of tumor-initiating cells (TICs), which drive recurrence and contribute to intra-tumoral heterogeneity through differentiation. These TICs are better able to escape extracellular matrix-imposed mechanical restrictions on invasion than their more differentiated progeny, and sensitization of TICs to extracellular matrix mechanics extends survival in preclinical models of GBM. However, little is known about the molecular basis of the relationship between TIC differentiation and mechanotransduction. Here we explore this relationship through a combination of transcriptomic analysis and studies with defined-stiffness matrices. We show that TIC differentiation induced by bone morphogenetic protein 4 (BMP4) suppresses expression of proteins relevant to extracellular matrix signaling and sensitizes TIC spreading to matrix stiffness. Moreover, our findings point towards a previously unappreciated connection between BMP4-induced differentiation, mechanotransduction, and metabolism. Notably, stiffness and differentiation modulate oxygen consumption, and inhibition of oxidative phosphorylation influences cell spreading in a stiffness- and differentiation-dependent manner. Our work integrates bioinformatic analysis with targeted molecular measurements and perturbations to yield new insight into how morphogen-induced differentiation influences how GBM TICs process mechanical inputs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antarctica, being the coldest, driest, and windiest continent on Earth, represents the most extreme environment in which a living organism can survive. Under constant exposure to harsh environmental threats, terrestrial Antarctica remains home to a great diversity of microorganisms, indicating that the soil bacteria must have adapted a range of survival strategies that require cell-to-cell communication. Survival strategies include secondary metabolite production, biofilm formation, bioluminescence, symbiosis, conjugation, sporulation, and motility, all of which are often regulated by quorum sensing (QS), a type of bacterial communication. Until now, such mechanisms have not been explored in terrestrial Antarctica. In this study, LuxI/LuxR-based quorum sensing (QS) activity was delineated in soil bacterial isolates recovered from Adams Flat, in the Vestfold Hills region of East Antarctica. Interestingly, we identified the production of potential homoserine lactones (HSLs) with chain lengths ranging from medium to long in 19 bacterial species using three biosensors, namely, Agrobacterium tumefaciens NTL4, Chromobacterium violaceum CV026, and Escherichia coli MT102, in conjunction with thin-layer chromatography (TLC). The majority of detectable HSLs were from Gram-positive species not previously known to produce HSLs. This discovery further expands our understanding of the microbial community capable of this type of communication, as well as provides insights into physiological adaptations of microorganisms that allow them to survive in the harsh Antarctic environment. IMPORTANCE Quorum sensing, a type of bacterial communication, is widely known to regulate many processes, including those that confer a survival advantage. However, little is known about communication by bacteria residing within Antarctic soils. Employing a combination of bacterial biosensors, analytical techniques, and genome mining, we found a variety of Antarctic soil bacteria speaking a common language, via LuxI/LuxR-based quorum sensing, thus potentially supporting survival in a mixed microbial community. This study reports potential quorum sensing activity in Antarctic soils and has provided a platform for studying physiological adaptations of microorganisms that allow them to survive in the harsh Antarctic environment., (Copyright © 2019 American Society for Microbiology.)

Background: Parents often express concerns about feeding difficulties in their child. We hypothesized that these parental concerns were associated with adverse growth status in early childhood. We aimed to determine the prevalence of such concerns and whether these concerns were associated with adverse growth status in early childhood., Methods: We performed a cross-sectional study among healthy children aged 12-36 months attending three well-baby clinics in three urban areas in Malaysia and Singapore between December 2016 and February 2017. Parents were interviewed for concerns about their child's feeding and presence of behavioral and organic red flags for feeding difficulties. We defined growth faltering as weight-for-age < 3rd centile and short stature as height-for-age < 3rd centile according to World Health Organization Growth Standards., Results: Of the 303 children studied (boys = 160, 52.8%; mean [± SD] chronological age at interview 21.3 [± 4.0] months), 13% (n = 38/292) had growth faltering and 19.5% (n = 50/256) had short stature. Overall, 36.3% (n = 110) of parents expressed concerns about their child's feeding behavior. Sixty-eight percent (n = 206) of parents reported presence of at least one behavioral and 18.5% (n = 56) had at least one organic red flag for feeding difficulties, respectively. 9.9% (n = 30) had both behavioral and organic red flags for feeding difficulties. Growth faltering was significantly associated with parental concern about feeding (odds ratio [OR] 3.049, p < 0.001), food refusal (OR 4.047, p < 0.001) and presence of at least one organic red flag (OR 2.625, p = 0.012)., Conclusion: We found that parental concerns about their child's feeding to be common. Presence of parental concern, food refusal in the child and presence of organic red flags for feeding difficulties are associated growth faltering in early childhood., (Copyright © 2019. Published by Elsevier B.V.)

Background: Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders., Methods: Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes., Results: Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase., Conclusion: Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.

Background: Hand hygiene compliance can be improved by strategies fostering collaborative efforts among healthcare workers (HCWs) through change agents. However, there is limited information about how change agents shape the social networks of work teams, and how this relates to organisational culture. The objectives of this study were to describe the influence of peer-identified change agents (PICAs) and management-selected change agents (MSCAs) on hand hygiene, perception of their leadership style by peers, and the role of the organisational culture in the process of hand hygiene promotion., Methods: This study, stratified in pre-, during, and post-intervention periods, was conducted between February 2017 and March 2018 in two wards at a tertiary care hospital in Malaysia. Hand hygiene promotion was facilitated either by PICAs (study arm 1) or MSCAs (study arm 2), and the two wards were randomly allocated to one of the two interventions. Outcomes were: 1) perceived leadership styles of PICAs and MSCAs by staff, vocalised during question and answer sessions; 2) the social network connectedness and communication patterns between HCWs and change agents by applying social network analysis; and 3) hand hygiene leadership attributes obtained from HCWs in the post-intervention period by questionnaires., Results: Hand hygiene compliance in study arm 1 and study arm 2 improved by from 48% (95% CI: 44-53%) to 66% (63-69%), and from 50% (44-55%) to 65% (60-69%), respectively. There was no significant difference between the two arms. Healthcare workers perceived that PICAs lead by example, while MSCAs applied an authoritarian top-down leadership style. The organisational culture of both wards was hierarchical, with little social interaction, but strong team cohesion. Position and networks of both PICAs and MSCAs were similar and generally weaker compared to the leaders who were nominated by HCWs in the post-intervention period. Healthcare workers on both wards perceived authoritative leadership to be the most desirable attribute for hand hygiene improvement., Conclusion: Despite experiencing successful hand hygiene improvement from PICAs, HCWs expressed a preference for the existing top-down leadership structure. This highlights the limits of applying leadership models that are not supported by the local organisational culture., Competing Interests: Competing interestsThe authors declare that they have no competing interests, (© The Author(s). 2019.)

Oil-secreting sebaceous glands (SGs) are critical for proper skin function; however, it remains unclear how different factors act together to modulate SG stem cells. Here, we provide functional evidence that each SG lobe is serviced by its own dedicated stem cell population. Upon ablating Notch signaling in different skin subcompartments, we find that this pathway exerts dual counteracting effects on SGs. Suppressing Notch in SG progenitors traps them in a hybrid state where stem and differentiation features become intermingled. In contrast, ablating Notch outside of the SG stem cell compartment indirectly drives SG expansion. Finally, we report that a K14:K5→K14:K79 keratin shift occurs during SG differentiation. Deleting K79 destabilizes K14 in sebocytes, and attenuates SGs and eyelid meibomian glands, leading to corneal ulceration. Altogether, our findings demonstrate that SGs integrate diverse signals from different niches and suggest that mutations incurred within one stem cell compartment can indirectly influence another., (Copyright © 2019 Elsevier Inc. All rights reserved.)