Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Prevalence and correlates of suicidal behaviours in a representative epidemiological youth sample in Hong Kong: the significance of suicide-related rumination, family functioning, and ongoing population-level stressors.

BACKGROUND: Young people are most vulnerable to suicidal behaviours but least likely to seek help. A more elaborate study of the intrinsic and extrinsic correlates of suicidal ideation and behaviours particularly amid ongoing population-level stressors and the identification of less stigmatising markers in representative youth populations is essential. METHODS: Participants (n = 2540, aged 15-25) were consecutively recruited from an ongoing large-scale household-based epidemiological youth mental health study in Hong Kong between September 2019 and 2021. Lifetime and 12-month prevalence of suicidal ideation, plan, and attempt were assessed, alongside suicide-related rumination, hopelessness and neuroticism, personal and population-level stressors, family functioning, cognitive ability, lifetime non-suicidal self-harm, 12-month major depressive disorder (MDD), and alcohol use. RESULTS: The 12-month prevalence of suicidal ideation, ideation-only (no plan or attempt), plan, and attempt was 20.0, 15.4, 4.6, and 1.3%, respectively. Importantly, multivariable logistic regression findings revealed that suicide-related rumination was the only factor associated with all four suicidal outcomes (all p < 0.01). Among those with suicidal ideation (two-stage approach), intrinsic factors, including suicide-related rumination, poorer cognitive ability, and 12-month MDE, were specifically associated with suicide plan, while extrinsic factors, including coronavirus disease 2019 (COVID-19) stressors, poorer family functioning, and personal life stressors, as well as non-suicidal self-harm, were specifically associated with suicide attempt. CONCLUSIONS: Suicide-related rumination, population-level COVID-19 stressors, and poorer family functioning may be important less-stigmatising markers for youth suicidal risks. The respective roles played by not only intrinsic but also extrinsic factors in suicide plan and attempt using a two-stage approach should be considered in future preventative intervention work.

Increased psychological distress among young people before and during the fifth wave of COVID-19 after two years of pandemic in Hong Kong: a 6-month longitudinal study.

BACKGROUND: Despite over two years of COVID-19 worldwide, the outbreak of the Omicron variant has given rise to an unprecedented surge of infection with diverse lockdown measures implemented globally. Whether the emergence of a new wave of COVID-19 could further affect mental health in the population after nearly two years of the pandemic remains to be addressed. Furthermore, whether changes in smartphone overuse behaviours and physical activity - both of which are particularly relevant to young people - would together contribute to changes in distress symptoms during this wave of COVID-19 was also examined. METHODS: A total of 248 young people from an ongoing household-based epidemiological study in Hong Kong who completed their baseline assessments prior to the Omicron variant outbreak, i.e., fifth wave of COVID-19 (July-November 2021), were invited for a 6-month follow-up study during this wave of infection (January-April 2022) (mean age = 19.7 years, SD = 2.7; 58.9% females). At both time points, levels of global distress symptoms, perceived stress, smartphone overuse, frequency of engagement in vigorous physical activity, and other potential risk and protective factors were assessed. RESULTS: The proportion of young people presenting moderate-to-severe distress (6-item Kessler Psychological Distress Scale ≥ 5) significantly increased from 45.6 to 54.4% during the fifth wave of COVID-19 (p < 0.010). Significantly increased levels of smartphone overuse and reduced days of vigorous physical activity were also observed during the fifth wave. Notably, increased smartphone overuse and reduced physical activity both additively and interactively contributed to elevated distress at 6 months, even after accounting for demographic characteristics, psychiatric history, childhood adversity, as well as baseline distress symptoms, resilience, and recent personal stressors. CONCLUSIONS: The findings suggest that the emergence of a new wave of COVID-19, specifically the Omicron outbreak, can further aggravate mental distress even after a protracted period of the pandemic. Awareness of the dynamic nature of COVID-19 is necessitated to address the pressing mental health needs of populations. Supporting young people in healthier patterns of smartphone use and physical activity can be helpful.

Impact of restrictive COVID-19 measures on daily momentary affect in an epidemiological youth sample in Hong Kong: An experience sampling study.

Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be explored. Experience sampling data were collected from 165 young people (aged 15-24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures - dine-in restrictions - on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure - school suspension - were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect (ß = -0.17, SE = 0.06, p = 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status (ß = -0.15, SE = 0.05, p = 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03183-y.

Transcatheter aortic valve implantation: initial experience in Hong Kong.

INTRODUCTION: Aortic stenosis is one of the most common valvular heart diseases in the ageing population. Patients with symptomatic severe aortic stenosis are at high risk of sudden death. Surgical aortic-valve replacement is the gold standard of treatment but many patients do not receive surgery because of advanced age or co-morbidities. Recently, transcatheter aortic valve implantation has been developed as an option for these patients. This study aimed to assess efficacy and safety of this procedure in the Hong Kong Chinese population. METHODS: Data for baseline patient characteristics, procedure parameters, and clinical outcomes up to 1-year post-implantation in a regional hospital in Hong Kong were collected and analysed. RESULTS: A total of 56 patients with severe aortic stenosis underwent the procedure from December 2010 to September 2015. Their mean (± standard deviation) age was 81.9 ± 4.8 years; 64.3% of them were male. Their mean logistic EuroSCORE was 22.6% ± 13.4%. After implantation, the mean aortic valve area improved from 0.70 cm2 ± 0.19 cm2 to 1.94 cm2 ± 0.37 cm2. Of the patients, 92% were improved by at least one New York Heart Association functional class. Stroke and major vascular complications occurred in one (1.8%) and five (8.9%) patients, respectively. A permanent pacemaker was implanted in seven (12.5%) patients. Both hospital and 30-day mortalities were 1.8%. The 1-year all-cause and cardiovascular mortality rates were 12.5% and 7.1%, respectively. CONCLUSIONS: Transcatheter aortic valve implantation has been developed as an alternative treatment for patients with symptomatic severe aortic stenosis who are deemed inoperable or high risk for surgery. Our results are very promising and comparable with those of major clinical trials.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Excessive fear of clusters of holes, its interaction with stressful life events and the association with anxiety and depressive symptoms: large epidemiological study of young people in Hong Kong.

BACKGROUND: Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples. AIMS: To examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress. METHOD: A total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested. RESULTS: The prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32-2.53), depression (OR = 1.78, 95% CI = 1.24-2.56) and stress (OR = 1.68, 95% CI = 1.11-2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose-response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life. CONCLUSIONS: Screening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.

A prospective study of bacterial flora in nasal cavity of patients with persistent allergic rhinitis.

It remains unanswered whether persistent allergic inflammation in nasal mucosa alters bacterial colonization and infection. The aim of this study was to investigate the bacterial flora in the nasal cavity of patients with persistent allergic rhinitis (PAR) and to correlate the bacteriological findings with presence of nasal symptoms, nasal eosinophil and neutrophil counts. A total of 255 subjects, aged between 6 - 74 years (mean 33.9 years) was randomly selected from a population-based rhinitis survey study in Singapore. All subjects went through a thorough medical history and nasal examinations. Serum specific IgE to a panel of common house dust mites, nasal cytological and microbiological examinations were performed. PAR was diagnosed in 107 patients and none of them had received previous regular therapy. There is a significant relationship between PAR and eosinophil grades, but not with neutrophil count. No statistically significant difference was found in quantitative and qualitative bacterial flora in nasal cavity between PAR patients and subjects with non-rhinitis or with non-allergic rhinitis. There is a significant inverse correlation between ongoing rhinorrhoea and quantitative bacterial load, and between signs of nasal mucosa (pale and edema) and the presence and type of bacterial pathogens. In conclusion, our study demonstrates that patients with untreated (or using PRN medicine) PAR do not result in a significant change in bacterial flora in their nasal cavity.

Impact of smartphone overuse on 1-year severe depressive symptoms and momentary negative affect: Longitudinal and experience sampling findings from a representative epidemiological youth sample in Hong Kong.

Smartphone overuse can have detrimental impacts on youth mental health. How it may be longitudinally associated with depressive symptoms and functioning, and with daily momentary affect, remains to be investigated. A total of 3,033 young people were consecutively recruited from a large-scale epidemiological youth mental health study in Hong Kong. A subsample (n = 936) was followed-up after 1 year, with experience sampling data collected from 177 participants. Separate multivariable logistic regression models were applied to examine the prospective associations between smartphone overuse and depressive symptoms, with multilevel models fitted to examine its associations with momentary affect. The prevalence of smartphone overuse in the Hong Kong youth population was 29.3%. Smartphone overuse was significantly associated with more depressive symptoms and functional impairments both cross-sectionally and longitudinally. The associations between smartphone overuse and 1-year depressive symptoms were significant, even when accounting for baseline symptoms, social media use, and other risk and protective factors. Baseline depressive symptoms, in contrast, were not associated with 1-year smartphone overuse after adjusting for baseline smartphone overuse. Smartphone overuse was also significantly associated with higher levels of momentary negative affect, even when accounting for depressive symptoms. Strategies to mitigate the impact of smartphone overuse can have important long-term implications.

Mouse studies of SARS coronavirus-specific immune responses to recombinant replication-defective adenovirus expressing SARS coronavirus N protein.

1. A recombinant adenovirus encoding SARS coronavirus(SARS-CoV) nucleocapsid protein (rAd-N) was constructed. 2. The ability of the rAd-N to induce anti-SARS-CoV N antibody production and cellular immune responses was evaluated in an HLA-A2.1/Kb transgenic mouse model.

Investigation of immunogenic T-cell epitopes in SARS virus nucleocapsid protein and their role in the prevention and treatment of SARS infection.

1. A novel HLA-A2.1-specific SARS coronavirus (SARS-CoV) nucleocapsid (N) protein epitope (N220-N228 LALLLLDRL) able to activate cytotoxic T cells in vitro has been identified. 2. When used with a single-chain-trimer system, the SARS-CoV N protein epitope (N220-N228 LALLLLDRL) can stimulate a cytotoxic T-cell response against N-protein expressing cells in the HLA-A2.1K(b) transgenic mouse model.

MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF.

Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biological functions, clinical significance and therapeutic implication of miR-377 in ESCC are largely unknown. In this study, we found that miR-377 expression was significantly downregulated in tumor tissue and serum of patients with ESCC. Both tumor tissue and serum miR-377 expression levels were positively correlated with patient survival. Higher serum miR-377 expression was inversely associated with pathologic tumor stage, distant metastasis, residual tumor status and chemoradiotherapy resistance. The roles of miR-377 in suppressing tumor initiation and progression, and the underlying molecular mechanisms were investigated. Results of in vitro and in vivo experiments showed that miR-377 overexpression inhibited the initiation, growth and angiogenesis of ESCC tumors as well as metastatic colonization of ESCC cells, whereas silencing of miR-377 had opposite effects. Mechanistically, miR-377 regulated CD133 and VEGF by directly binding to their 3' untranslated region. Moreover, systemic delivery of formulated miR-377 mimic not only suppressed tumor growth in nude mice but also blocked tumor angiogenesis and metastasis of ESCC cells to the lungs without overt toxicity to mice. Collectively, our study established that miR-377 plays a functional and significant role in suppressing tumor initiation and progression, and may represent a promising non-invasive diagnostic and prognostic biomarker and therapeutic strategy for patients with ESCC.

Modulation of Ca2+-dependent anion secretion by protein kinase C in normal and cystic fibrosis pancreatic duct cells.

The study investigated the role of protein kinase C (PKC) in the modulation of agonist-induced Ca2+-dependent anion secretion by pancreatic duct cells. The short-circuit current (ISC) technique was used to examine the effect of PKC activation and inhibition on subsequent ATP, angiotensin II and ionomycin-activated anion secretion by normal (CAPAN-1) and cystic fibrosis (CFPAC-1) pancreatic duct cells. The ISC responses induced by the Ca2+-mobilizing agents, which had been previously shown to be attributed to anion secretion, were enhanced in both CAPAN-1 and CFPAC-1 cells by PKC inhibitors, staurosporine, calphostin C or chelerythrine. On the contrary, a PKC activator, phorbol 12-myristate 13-acetate (PMA), was found to suppress the agonist-induced ISC in CFPAC-1 cells and the ionomycin-induced ISC in CAPAN-1 cells. An inactive form of PMA, 4alphad-phorbol 12, 13-didecanote (4alphaD), was found to exert insignificant effect on the agonist-induced ISC, indicating a specific effect of PMA. Our data suggest a role of PKC in modulating agonist-induced Ca2+-dependent anion secretion by pancreatic duct cells. Therapeutic strategy to augment Ca2+-activated anion secretion by cystic fibrosis pancreatic duct cells may be achieved by inhibition or down-regulation of PKC.

Differential expression of a stress-modulating gene, BRE, in the adrenal gland, in adrenal neoplasia, and in abnormal adrenal tissues.

Genes that modulate the action of hormones and cytokines play a critical role in stress response, survival, and in growth and differentiation of cells. Many of these biological response modifiers are responsible for various pathological conditions, including inflammation, infection, cachexia, aging, genetic disorders, and cancer. We have previously identified a new gene, BRE, that is responsive to DNA damage and retinoic acid. Using multiple-tissue dot-blotting and Northern blotting, BRE was recently found to be strongly expressed in adrenal cortex and medulla, in testis, and in pancreas, whereas low expression was found in the thyroid, thymus, small intestine and stomach. In situ hybridization and immunohistochemical staining indicated that BRE was strongly expressed in the zona glomerulosa of the adrenal cortex, which synthesizes and secretes the mineralocorticoid hormones. It is also highly expressed in the glial and neuronal cells of the brain and in the round spermatids, Sertoli cells, and Leydig cells of the testis, all of which are associated with steroid hormones and/or TNF synthesis. However, BRE expression was downregulated in human adrenal adenoma and pheochromocytoma, whereas its expression was enhanced in abnormal adrenal tissues of rats chronically treated with nitrate or nitrite. These data, taken together, indicate that the expression of BRE is apparently associated with steroids and/or TNF production and the regulation of endocrine functions. BRE may play an important role in the endocrine and immune system, such as the cytokine-endocrine interaction of the adrenal gland.

Telomerase activity in thyroid malignancy.

Telomerase activity seems to play a role in the development and pathogenesis of thyroid carcinoma. Its incidence of expression and its application as a tumor marker remain to be elucidated. Thyroid tissues obtained during thyroidectomy from 1996-1998 were rapidly frozen and stored at -80 degrees C until processed. Telomerase activity was determined using telomeric repeat amplification protocol (TRAP). Histology of the tissue examined (67 benign and 59 malignant) was reviewed. Telomerase activity was detected in 15 of 52 papillary carcinomas (29%); 1 of 1 thyroid lymphoma (100%); 1 of 2 anaplastic carcinomas (50%); and 2 of 16 lymphocytic thyroiditis specimens (13%). Telomerase activity was not detectable in 35 normal thyroid, 9 follicular adenoma, 7 nodular hyperplasia, 2 follicular carcinoma, and 2 medullary carcinoma. Lymphocytic thyroiditis was detected in 8 of 37 (22%) apparently normal thyroid tissues adjacent to papillary thyroid carcinoma and telomerase activity was present in 2 of these 8 specimens (25%). In conclusion, telomerase does not appear to be frequently activated in papillary thyroid carcinoma. The association of lymphocytic thyroiditis with papillary thyroid carcinoma may limit its clinical usefulness as a tumor marker.

The use of a distal occlusion balloon protection device in acute coronary syndrome.

We report our early experience in using the PercuSurge GuardWire Plus system as a distal protection device in patients with acute coronary syndrome and acute myocardial infarction. Forty-three patients received percutaneous coronary intervention with the GuardWire Plus system. Thirteen had unstable angina, five had non-Q myocardial infarction and 25 had ST segment elevation myocardial infarction. Forty-one target lesions were in native coronary vessels and two were in saphenous vein grafts. Total occlusion occurred in 18 patients. The mean occlusion time by the distal protective balloon was 262.8 +/- 114.1 s. Preoperatively, TIMI 0 flow was present in 18, TIMI II flow in two and TIMI III flow in 23 patients. Post-operatively, TIMI II and TIMI III flow were established in two and 41 patients, respectively. All procedures were successful and the GuardWire Plus system was successfully deployed in all but two patients. There was no procedure-related major adverse clinical event. There was no major adverse clinical event at 30 days. There was no device-related complication. We believe that the GuardWire Plus system is safe and feasible in patients with acute coronary syndrome and acute myocardial infarction.

Species differences in the urinary excretion of the novel primary amine conjugate: tocainide carbamoyl O-beta-D-glucuronide.

The metabolism of the antiarrhythmic drug tocainide (I) has been shown previously to occur via a novel pathway involving the addition of carbon dioxide to the primary amine nitrogen of I followed by conjugation with glucuronic acid. The product of this reaction, tocainide carbamoyl O-beta-D-glucuronide (II), the principal metabolite of I in humans, has been found to cyclize under strongly basic conditions to form 3-(2,6-xylyl)-5-methylhydantoin (III). Thus, evidence for the existence of II can be obtained by two different procedures: conversion of II to III in the presence of strong base and by hydrolysis of II with beta-glucuronidase. The principal purpose of the present investigation was to identify suitable species for studies of the mechanism involved in the formation of II, as well as to find an animal model suitable for toxicological evaluation of tocainide and structurally related compounds. Eight animal species were examined to identify those capable of metabolizing I into II. The fraction of an intraperitoneal dose excreted in urine as II was estimated by measurement of tocainide released by beta-glucuronidase mediated hydrolysis of urine and by the quantitation of III formed after alkalinization of urine samples. Urinary recovery of unchanged drug ranged from 9.5% of the dose in the gerbil to 48.7% in the cat. The percent of the dose excreted in urine as acid hydrolyzable conjugates ranged from less than 1% in the gerbil to a mean of 13% in the rabbit. Guinea pigs, dogs, cats, rabbits, and pigtail monkeys excreted amounts of II ranging from 0.2 to 2.4% of the dose. Thus, none of the species appeared to be a suitable model for the study of the mechanism of formation of II because of the quantitative insignificance of this pathway.

Treatment of long, diffuse in-stent restenosis with sirolimus-eluting stents.

Treatment of long, diffuse in-stent restenosis remains a therapeutic challenge. We report the successful use of multiple sirolimus-eluting stents (three 33-mm long stents) in a long, diffuse in-stent restenotic lesion. No major adverse cardiovascular events, including acute/subacute/delayed stent thrombosis, were noted at ten months. Angiography at six months showed widely patent stents with 19% restenosis only at the worst segment.