A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic

BackgroundLifestyle of children and adolescents have changed extensively during the COVID-19 pandemic due to school suspension and social distancing measures, which can affect their sleep health. Existing studies in the area used convenient samples and focused on the initial months of the pandemic. MethodAs part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. We investigated the pandemics effects on sleep parameters using multivariate regression, adjusting for age, sex, household income, seasonality and presence of mental disorders, and the effects moderators and mediators. FindingsBetween September 1, 2019 and June 2, 2021, 791 primary and 442 school students were recruited and analysed. After correcting for multiple testing, being assessed during COVID predicted a longer sleep latency in primary and secondary school students in school days (95% CI = 1.0-5.2 minutes, adjusted p-value = 0.010; and 95% CI= 3.9-13.0 minutes, adjusted p-value =0.004, respectively) and non-school days (95% CI = 1.7-7.2 minutes, adjusted p-value = 0.005; 95% CI = 3.4-13.7 minutes, adjusted p-value = 0.014, respectively). Low household income was a moderator for later bedtime (adjusted p-value = 0.032) and later sleep onset (adjusted p-value = 0.043) during non-school days among secondary school students. Sex and digital leisure time were not moderator and mediator of the pandemics effect on sleep parameters, respectively. InterpretationChanges associated with the COVID-19 pandemic have a widespread and enduring effect on sleep health of school-aged students in Hong Kong. Household income play a role in adolescents sleep healths resilience against these changes, and anti-epidemic measures effects on the health gap of the youth should be considered. FundingGovernment of the Hong Kong Special Administrative Region, Food and Health Bureau, Health and Medical Research Fund (Ref. No.: MHS-P1(Part 1)-CUHK).

Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study

Background and AimsThe incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients. MethodsWe identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. ResultsWe isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. ConclusionsIn this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.

Outcomes of SARS-CoV-2 Infection in Patients with Chronic Liver Disease and Cirrhosis: a N3C Study

Background and AimsIn patients with chronic liver diseases (CLD) with or without cirrhosis, existing data on the risk of adverse outcomes with SARS-CoV-2 infection have been mixed or have limited generalizability. We used the National COVID Cohort Collaborative (N3C) Data Enclave, a harmonized electronic health record (EHR) dataset of 5.9 million nationally-representative, diverse, and gender-balanced patients, to describe outcomes in patients with CLD and cirrhosis with SARS-CoV-2. MethodsWe identified all chronic liver diseases patients with and without cirrhosis who had SARS-CoV-2 testing documented in the N3C Data Enclave as of data release date 5/15/2021. The primary outcome was 30-day all-cause mortality. Survival analysis methods were used to estimate cumulative incidences of death, hospitalization, and mechanical ventilation, and to calculate the associations of SARS-CoV-2 infection, presence of cirrhosis, and demographic and clinical factors to 30-day mortality. ResultsWe isolated 217,143 patients with CLD: 129,097 (59%) without cirrhosis and SARS-CoV-2 negative, 25,844 (12%) without cirrhosis and SARS-CoV-2 positive, 54,065 (25%) with cirrhosis and SARS-CoV-2 negative, and 8,137 (4%) with cirrhosis and SARS-CoV-2 positive. Among CLD patients without cirrhosis, 30-day all-cause mortality rates were 0.4% in SARS-CoV-2 negative patients and 1.8% in positive patients. Among CLD patients with cirrhosis, 30-day all-cause mortality rates were 4.0% in SARS-CoV-2 negative patients and 9.7% in positive patients. Compared to those who tested SARS-CoV-2 negative, SARS-CoV-2 positivity was associated with more than two-fold (aHR 2.43, 95% CI 2.23-2.64) hazard of death at 30 days among patients with cirrhosis. Compared to patients without cirrhosis, the presence of cirrhosis was associated with a three-fold (aHR 3.39, 95% CI 2.96-3.89) hazard of death at 30 days among patients who tested SARS-CoV-2 positive. Age (aHR 1.03 per year, 95% CI 1.03-1.04) was associated with death at 30 days among patients with cirrhosis who were SARS-CoV-2 positive. ConclusionsIn this study of nearly 220,000 CLD patients, we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.43-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 were associated with 3.39-times mortality hazard. Compared to previous studies, our use of a nationally-representative, diverse, and gender-balanced dataset enables wide generalizability of these findings.

The Practice of Gastrointestinal Motility Laboratory During COVID-19 Pandemic: Position Statements of the Asian Neurogastroenterology and Motility Association (ANMA-GML-COVID-19 Position Statements)

During the Coronavirus Disease 2019 (COVID-19) pandemic, practices of gastrointestinal procedures within the digestive tract require special precautions due to the risk of contraction of severe acute respiratoy syndrome coronavirus-2 (SARS-CoV-2) infection. Many procedures in the gastrointestinal motility laboratory may be considered moderate to high-risk for viral transmission. Healthcare staff working in gastrointestinal motility laboratories are frequently exposed to splashes, air droplets, mucus, or saliva during the procedures. Moreover, some are aerosol-generating and thus have a high risk of viral transmission. There are multiple guidelines on the practices of gastrointestinal endoscopy during this pandemic. However, such guidelines are still lacking and urgently needed for the practice of gastrointestinal motility laboratories. Hence, the Asian Neurogastroenterology and Motility Association had organized a group of gastrointestinal motility experts and infectious disease specialists to produce a position statement paper based-on current available evidence and consensus opinion with aims to provide a clear guidance on the practices of gastrointestinal motility laboratories during the COVID-19 pandemic. This guideline covers a wide range of topics on gastrointestinal motility activities from scheduling a motility test, the precautions at different steps of the procedure to disinfection for the safety and well-being of the patients and the healthcare workers. These practices may vary in different countries depending on the stages of the pandemic, local or institutional policy, and the availability of healthcare resources. This guideline is useful when the transmission rate of SARS-CoV-2 is high. It may change rapidly depending on the situation of the epidemic and when new evidence becomes available.

Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones as potential HIV-1 inhibitors

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Comparative evaluation of the biocompatible and physical-chemical properties of poly(lactide-co-glycolide) and polydopamine as coating materials for bacterial cellulose.

The aim of this study was to investigate the influence of poly(lactide-co-glycolide) (PLGA) and polydopamine (PDA) as coating materials on the tensile strength, surface performance, in vitro cell behavior and the in vivo material-tissue reaction of bacterial cellulose (BC) membranes. The coated membranes were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and scanning electron microscopy (SEM), demonstrating that the PDA forms the dispersion phase and penetrates into the BC substrates while PLGA only adheres to the BC surface. Mechanical tests and fractured surface morphology reveal that penetration of PDA into BC membranes enhances the mechanical strength by strongly bonding the nanofibers. The PLGA coated BC membrane obtained by adhesion debonds from the BC substrate under stress, leading to a decrease in the mechanical strength of the membrane. The in vitro cell culture experiments were established to assess cell attachment and spreading by SEM and DAPI (4',6-diamidino-2-phenylindole) staining and expression of collagen I, which showed a better performance on the PDA-BC than on the PLGA-BC and bare BC membranes. However, the in vivo results of the rabbit back implantation indicated that BC membrane surface modification by PDA is not effective for cell proliferation and collagen accumulation when compared to bare and PLGA coated BC, whereas PLGC-BC were surrounded by a thicker layer of connective tissues with slight neovascularization demonstrating superior tissue integration. PDA based materials still have a long way to go before clinical applications. However, PLGA coating has excellent biocompatibility in clinical as well as in experimental use.

The maintenance effect of cognitive-behavioural treatment groups for the Chinese parents of children with intellectual disabilities in Melbourne, Australia: a 6-month follow-up study.

BACKGROUND: Caring for a child with intellectual disability can be stressful. No data on the longer-term effects of cognitive-behavioural treatment (CBT) on parents from a Chinese-speaking background who have children with intellectual disabilities are available in the literature. This study attempted to fill this research gap by examining the maintenance effect of CBT among the Chinese parents of such children in Melbourne, Australia. METHOD: Thirty-nine participants took part in our CBT groups and attended follow-up meetings. A questionnaire comprising four instruments, the Parenting Stress Index (PS) - Parent Domain, General Health Questionnaire-12 (GHQ-12), Abbreviated Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-18) and Dysfunctional Attitude Scale (DAS), was administered to the participants at the pre- and post-test stage and at the 6-month follow-up. RESULTS: One-way repeated-measures analyses of variance revealed significant time and group effects in the PS (F(2,27) = 16.93, P < 0.001), Q-LES-Q-18 (F(2,27) = 15.98, P < 0.001), GHQ-12 (F(2,27) = 81.93, P < 0.001) and DAS (F(2,27) = 15.50, P < 0.001) scores at the three measurement times. The participants continued to maintain significant improvements in mental health and quality of life and declines in the severity of parenting stress and dysfunctional attitudes at the 6-month follow-up. Effect size analyses revealed mostly large differences in the foregoing measurements (Cohen's d = 0.76-2.18) between the pre-test and 6-month follow-up. Employing a cut-off score of 3/4 in the GHQ-12 to identify at-risk and not-at-risk cases, approximately 90.5% of the participants could be classified as not-at-risk at the follow-up. Lastly, regression analyses showed that changes in DAS scores significantly predicted changes in the GHQ-12 and Q-LES-Q-18 scores at the follow-up. CONCLUSIONS: This study provides preliminary evidence of the 6-month maintenance effect of CBT groups for the Melbourne-resident Chinese parents of children with intellectual disabilities.

Hopelessness, parent-adolescent communication, and suicidal ideation among Chinese adolescents in Hong Kong.

Based on the responses of 5,557 Chinese secondary students in Hong Kong, the relationships among perceived hopelessness, family functioning, and suicidal ideation were examined. Results showed that suicidal ideation was positively related to hopelessness, but negatively related to parent-adolescent communication. Compared with father-adolescent communication, mother-adolescent communication generally had a stronger association with adolescent suicidal ideation. It was further found that the linkage between hopelessness and adolescent suicidal ideation was stronger under a low parent-adolescent communication condition, thus suggesting the moderating effect of parent-adolescent communication on the effect of hopelessness on suicidal ideation. The theoretical and practical implications of the findings are discussed.

Social problem solving, family functioning, and suicidal ideation among Chinese adolescents in Hong Kong.

Based on the responses of 5,557 Chinese secondary students in Hong Kong, the relationship among social problem solving, perceived family functioning, and suicidal ideation were examined in this study. Results showed that suicidal ideation was negatively related to social problem solving and family functioning. It was further found that the linkage between social problem solving and adolescent suicidal ideation was stronger under high family functioning relative to low family functioning, thus suggesting the moderating effect of family functioning on the effect of social problem solving on suicidal ideation. The theoretical and practical implications of the findings are discussed.

Socio-demographic correlates of suicidal ideation among Chinese adolescents in Hong Kong.

Several socio-demographic correlates, including age of adolescents, family economic status, parental marital status, parental occupational status and parental educational level of adolescent suicidal ideation among Chinese adolescents (N = 5,557) were examined in this study. The results showed that older adolescents had a significantly higher level of suicidal ideation than did younger ones. Adolescents living in non-intact families had a significantly higher level of suicidal ideation than those in intact families. Adolescents with lower socioeconomic status (indexed by economic disadvantage, parental occupational status, and parental educational attainment) displayed higher levels of suicidal ideation than did adolescents with higher suicidal ideation. Although these socio-demographic correlates were significantly related to suicidal ideation, the practical significance was not high.

Global standardisation of HbA1c

HbA1c is used for assessing glycaemic control in patients with diabetes. It is also used for treatment goals and as a target for therapeutic intervention. The Direct Control and Complications Trial in the USA showed that HbA1c can be used to predict the risk of complications. Hence, it is important for HbA1c assays to be standardised. The National Glycohemoglobin Standardization Program (NGSP) in the USA was formed in 1996 so that HbA1c results from different laboratories would be comparable to those reported in the DCCT study. There were also HbA1c standardisation programmes in Sweden and Japan. These three standardisation programmes are, in fact, direct comparison methods (DCMs), and yield different HbA1c results. In 1994, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group on Standardisation of HbA1c. This working group has developed a global HbA1c reference system with very much improved intra-assay and inter-assay coefficients of variation. Recommendations have been made to report HbA1c results as IFCC-HbA1c values in SI units (mmol HbA1c/mol Hb) and NGSP-HbA1c (%) as well as estimated average glucose (eAG), once a tight relationship has been shown to exist between eAG and HbA1c.

Effect of cathepsin D and prostate specific antigen on latent transforming growth factor-beta in breast cancer cell lines

Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.

Prevention of type 2 diabetes

The prevalence of diabetes is increasing worldwide. The World Health Organisation has estimated that there will be around 300 million diabetics by 2025. The largest increase will occur in Asia. The prevalence of type 2 diabetes is increasing due to a combination of factors: increasing lifespan, sedentary lifestyle, excessive intake of high energy foods, increasing prevalence of overweight/obese people. The Finnish Diabetes Prevention Study Group has clearly shown that changes in the lifestyle of both overweight men and women with impaired glucose tolerance can reduce the incidence of type 2 diabetes by 58%. This finding was confirmed by the Diabetes Prevention Programme which found that lifestyle intervention in individuals with impaired fasting glucose or impaired glucose tolerance reduced the risk of developing type 2 diabetes by 58%, whereas treatment with metformin reduced the risk of type 2 diabetes by only 31%. Both acarbose and troglitazone have also been shown to reduce the progression to diabetes in individuals who are at high risk of developing type 2 diabetes. Since the cure for diabetes remains some way off our concerted efforts should be directed at prevention of diabetes in order to curb the increasing prevalence of diabetes worldwide. Lifestyle changes are more beneficial than long term drug therapy in the prevention of diabetes and should be actively promoted.