Search

A "chemical linearization" approach was applied to synthetic peptide macrocycles to enable their de novo sequencing from mixtures using nanoliquid chromatography-tandem mass spectrometry (nLC-MS/MS). This approach─previously applied to individual macrocycles but not to mixtures─involves cleavage of the peptide backbone at a defined position to give a product capable of generating sequence-determining fragment ions. Here, we first established the compatibility of "chemical linearization" by Edman degradation with a prominent macrocycle scaffold based on bis -Cys peptides cross-linked with the m -xylene linker, which are of major significance in therapeutics discovery. Then, using macrocycle libraries of known sequence composition, the ability to recover accurate de novo assignments to linearized products was critically tested using performance metrics unique to mixtures. Significantly, we show that linearized macrocycles can be sequenced with lower recall compared to linear peptides but with similar accuracy, which establishes the potential of using "chemical linearization" with synthetic libraries and selection procedures that yield compound mixtures. Sodiated precursor ions were identified as a significant source of high-scoring but inaccurate assignments, with potential implications for improving automated de novo sequencing more generally.

Background: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia., Methods: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone ( n = 11), combined-exercise program and nutrition supplement ( n = 23), and waitlist control group ( n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests., Results: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups ( p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes ( RASGRP1 , BIN1 , LEF1 , ANXA6 , IL-7R , LRRN3 , and PRKCQ ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction., Conclusions: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.

Objective: This study examined Na intake and identified the major food sources of Na in healthy Chinese adults aged ≥50 years in Hong Kong., Design: Participants who completed a baseline assessment of a randomised controlled trial assessing the effectiveness of exercise and nutrition supplementation on improving physical and cognitive functions were included. A single 24-h urine sample and a 3-d diet record were used to measure urinary Na excretion and dietary intake, respectively. The compliances to the WHO (<5 g/d) and China Nutrition Society (<6 g/d) recommendations for salt intake were assessed based on the urinary Na excretion. The relative contribution of sixteen food groups to the dietary Na intake was expressed as percentages. Associations between food groups and urinary Na excretion were analysed using multiple linear regression., Setting: Community facilities., Participants: Totally, 114 healthy Chinese adults (mean age 60·6 years, 55 % women)., Results: The mean urinary Na excretion over 24-h was 2876·6 ± 1249·4 mg/d (7·3 ± 3·2 g salt/d). Overall, 22·8 % of participants met the WHO recommendation and 34·2 % met the Chinese Nutrition Society recommendation for salt intake. The major food sources of dietary Na intake were condiments (42·4 %), cereals and their products (16·8 %) and soups (13·5 %). Higher intakes of seafood and nuts were associated with lower urinary Na excretion., Conclusions: Public health strategies should target healthy Chinese adults in Hong Kong to modify the current patterns of Na intake. Targeting condiments, cereals and their products and soups will be an important strategy to reduce their Na intake.

Background & Aims: Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response., Methods: A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m 2 was used to define non-obese NAFLD., Results: Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m 2 , respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group., Conclusions: Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population., Lay Summary: Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Gestational diabetes mellitus (GDM) is of public health concern. This trial examined whether a clinically proven lifestyle modification program (LMP) in early pregnancy was superior to routine antenatal care in improving GDM, maternal and infant outcomes. Chinese pregnant women at risk of GDM (n = 220) were recruited at or before 12-week gestation and randomized to either a LMP group or a routine care control group. Eighty subjects completed a dietitian-led LMP including dietary and exercise components from early pregnancy till 24-week gestation. Data were compared with those of 86 control subjects. Twenty three (26.7%) control subjects and 20 (25.0%) LMP subjects developed GDM (p = 0.798). The proportion of infants born large for gestational age and macrosomia was similar between groups. The LMP group showed a lower proportion of excessive gestational weight gain (GWG). Subgroup analysis suggested that those with higher LMP adherence showed more desirable dietary composition and energy intake, and lower proportion of excessive GWG compared with the low LMP adherence group and the control group. The potential effect of LMP on GDM and other maternal and infant outcomes, in particular GWG, as well as barriers for making lifestyle changes warrant further investigations (ClinicalTrials.gov NCT02368600).

Goals: To study the long-term outcome after cessation of antiviral therapy in immune-tolerant patients., Background: Experience in the treatment of immune-tolerant chronic hepatitis B is scanty. Some immune-tolerant patients may receive temporary antiviral therapy, such as for prevention of vertical transmission at pregnancy or prophylaxis for chemotherapy., Study: This was a follow-up study of a phase 2 trial at 2 centers. Immune-tolerant patients received tenofovir disoproxil fumarate and/or emtricitabine for 4 years and were followed for another 4 years after treatment cessation. Virological relapse was defined as hepatitis B virus (HBV) DNA>2000 IU/mL; clinical relapse was defined as HBV DNA>2000 IU/mL; and alanine aminotransferase (ALT)>2 times the upper limit of normal., Results: In total, 20 patients stopped treatment and were followed up for 206±14 weeks. All patients developed virological relapse at posttreatment week 4 (HBV DNA, 7.07±1.45 log IU/mL). A total of 10 (50%) patients developed clinical relapse at 15±11 weeks (highest ALT, 1149 U/L). In total, 11 (55%) patients were restarted on antiviral therapy; 4 achieved complete HBV DNA suppression and 1 achieved hepatitis B e antigen (HBeAg) seroconversion. Among the 9 patients not restarted on therapy, 2 patients had HBeAg seroconversion with normal ALT and HBV DNA of 7.12 and 1.62 IU/mL, respectively. The remaining 7 untreated patients continued to have positive HBeAg, high HBV DNA, and normal ALT., Conclusions: Rapid virological relapse is universal and clinical relapse is common after stopping antiviral therapy in patients with immune-tolerant chronic hepatitis B. HBeAg seroconversion is rare regardless of treatment reinitiation.

Introduction: A survey conducted during 2005 to 2007 by the Centre for Food Safety in Hong Kong suggested that only 5% of the local population had a sufficient dietary intake of iodine. The study, however, was limited as biochemical data (ie urinary iodine concentration) were lacking. Pregnant women are vulnerable to iodine deficiency because of their increased requirement. Recent studies have shown that iodine deficiency in early pregnancy is associated with poorer cognitive development in early childhood. This study reports the iodine status of women during early gestation at an obstetric unit in Hong Kong., Methods: Healthy pregnant women with no history of hyperemesis gravidarum were enrolled into a study when they first made a booking in an antenatal clinic of a public hospital to investigate their iodine status during early pregnancy. All subjects were asked to collect their morning urine for measurement of iodine and creatinine levels. Daily dietary intake of iodine was assessed in a subgroup of participants by structured interview using a standard food frequency questionnaire., Results: A total of 600 pregnant women were enrolled at a median of 7.0 weeks of gestation. The median urinary iodine concentration and urinary iodine-to-creatinine ratio were 100 μg/L and 98 μg/g, respectively; 429 (71.5%) participants had iodine insufficiency according to the World Health Organization classification. Daily dietary intake of iodine was assessed in 146 participants. The median daily intake of iodine was 69.5 μg and 122 (83.6%) participants had an intake below the 250 μg recommended during pregnancy by the World Health Organization., Conclusions: Local pregnant women continue to have an inadequate dietary intake of iodine and remain iodine-deficient.

Objectives: Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD., Methods: A total of 911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese NAFLD., Results: The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs. 5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1; P<0.001)., Conclusions: One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.

Background: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth., Aims: To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia., Methods: Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays., Results: Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers., Conclusions: Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies., (© 2015 John Wiley & Sons Ltd.)

Background & Aims: Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests., Methods: This was a prospective cohort study. The intrahepatic triglyceride (IHTG) content was measured serially with proton-magnetic resonance spectroscopy in community subjects. Transient elastography was performed to assess liver fibrosis., Results: 565 subjects (mean age 48 years, 62.7% women) without NAFLD at baseline underwent follow-up assessment after a median interval of 47 months (range 34-60 months). 78 (13.8%) subjects developed incident fatty liver with a mean IHTG content of 8.9% (SD 5.3%). 16 (20.5%) subjects had an IHTG content ⩾ 11.0% suggestive of moderate to severe steatosis. After excluding 2 men with significant alcohol consumption, the population incidence of NAFLD at 3-5 years was 13.5% (95% CI 10.6-16.3%; 3.4% per year). Only 1 subject with incident NAFLD had high liver stiffness (11.1 kPa) suggestive of advanced fibrosis. Metabolic syndrome at baseline was the strongest predictor of incident fatty liver. Incident central obesity developed in 31.0% of subjects with incident fatty liver and 5.6% of those without (p<0.001). No subject with incident fatty liver had regression of impaired fasting glucose, which occurred in 51.1% of those without incident fatty liver (p=0.001)., Conclusions: 13.5% of the Hong Kong Chinese adult population develop NAFLD in 3-5 years, but few have severe steatosis or advanced fibrosis. Metabolic syndrome is the most important risk factor of incident NAFLD., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients., Methods: This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy., Results: One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group., Conclusion: Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The Pipeline embolization device (PED) is one of the flow-diverting stents approved for the treatment of unruptured large or wide-necked cerebral aneurysms in 2011(1). Its use has now been extended to the treatment of recently ruptured dissecting cerebral aneurysm, carotid pseudoaneurysm from radiation injury, and blister aneurysms(2,3). We aimed to evaluate the effectiveness of utilizing the PED as a primary treatment for ruptured dissecting intracranial aneurysms. A single center retrospective review was conducted for all patients primarily treated with PED for acute subarachnoid hemorrhage (SAH) from ruptured dissecting cerebral aneurysms between December 2010 and February 2013. Patients were followed up with CT angiogram (CTA) or digital subtraction angiogram (DSA). Eight patients with a total of eight dissecting aneurysms were identified. The mean duration from SAH to treatment was 2.5 days. Six of the aneurysms arose from vertebral arteries and two from the basilar artery. Immediate check-DSA confirmed satisfactory contrast stasis in all eight cases, and complete aneurysmal obliteration was achieved at six months. There were two (25%) procedure-related complications, but no major procedure-related complications, such as thromboembolic events or rebleeding from aneurysm were encountered. The PED is a feasible treatment option for ruptured dissecting cerebral aneurysms in acute phase. According to our experience, using PED as flow-diverters in acute SAH does not significantly increase the complication risks or mortality rate if the antiplatelet regime is carefully monitored. Future studies shall evaluate the optimal antiplatelet regimen for using the PED in the acute phase.

Objectives: Nonalcoholic fatty liver disease is the most common chronic liver disease. Fatty pancreas has also been described but is difficult to assess. It is now possible to measure pancreatic and liver fat accurately with magnetic resonance imaging (MRI). We aimed to define the normal range of pancreatic fat and identify factors associated with fatty pancreas. In addition, the effect of fatty liver and fatty pancreas on insulin resistance (IR) and pancreatic β-cell function was studied., Methods: Fat-water MRI and proton-magnetic resonance spectroscopy were performed on 685 healthy volunteers from the general population to measure pancreatic and liver fat, respectively. On the basis of fasting plasma glucose and insulin levels, the IR and β-cell function were assessed using the homeostasis model assessment (HOMA)., Results: Among subjects without significant alcohol consumption or any component of metabolic syndrome, 90% had pancreatic fat between 1.8 and 10.4%. Using the upper limit of normal of 10.4%, 110 (16.1%; 95% confidence interval 13.3-18.8%) subjects had fatty pancreas. On multivariable analysis, high serum ferritin, central obesity, and hypertriglyceridemia were independent factors associated with fatty pancreas. Subjects with both fatty pancreas and fatty liver had higher HOMA-IR than did those with either condition alone. Fatty pancreas was not associated with HOMA-β after adjusting for liver fat and body mass index., Conclusions: In all, 16.1% of this community cohort of adult Hong Kong Chinese volunteers had a fatty pancreas by our definition. Central obesity, hypertriglyceridemia, and hyperferritinemia are associated with fatty pancreas. Individuals with fatty pancreas have increased IR.

Background: The rs738409 GG variant in patatin-like phospholipase 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern., Aim: To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD., Methods: Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food-frequency questionnaire., Results: The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern., Conclusions: The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors., (© 2014 John Wiley & Sons Ltd.)

Background: The role of a low glycemic index (GI) diet in the management of adolescent obesity remains controversial. In this study, we aim to evaluate the impact of low GI diet versus a conventional Chinese diet on the body mass index (BMI) and other obesity indices of obese adolescents., Methods: Obese adolescents aged 15-18 years were identified from population-recruited, territory-wide surveys. Obesity was defined as BMI ≥95th percentile of Hong Kong local age- and sex-specific references. Eligible subjects were randomized to either an intervention with low GI diet (consisting of 45-50% carbohydrate, 30-35% fat and 15-20% protein) or conventional Chinese diet as control (consisting of 55-60% carbohydrate, 25-30% fat and 10-15% protein). We used random intercept mixed effects model to compare the differential changes across the time points from baseline to month 6 between the 2 groups., Results: 104 obese adolescents were recruited (52 in low GI group and 52 in control group; 43.3% boys). Mean age was 16.7 ± 1.0 years and 16.8 ±1.0 years in low GI and control group respectively. 58.7% subjects completed the study at 6 months (65.4% in low GI group and 51.9% in control group). After adjustment for age and sex, subjects in the low GI group had a significantly greater reduction in obesity indices including BMI, body weight and waist circumference (WC) compared to subjects in the control group (all p <0.05). After further adjustment for physical activity levels, WC was found to be significantly lower in the low GI group compared to the conventional group (p = 0.018)., Conclusion: Low GI diet in the context of a comprehensive lifestyle modification program may be an alternative to conventional diet in the management of obese adolescents., Trial Registration Number: ClinicalTrials.gov Ref. No: NCT01278563.

With global aging population, age-related cognitive decline becomes epidemic. Lifestyle-related factor is one of the key preventative measures. Dietary pattern analysis which considers dietary complexity has recently used to examine the linkage between nutrition and cognitive function. A priori approach defines dietary pattern based on existing knowledge. Results of several dietary pattern scores were summarized. The heterogeneity of assessment methods and outcome measurements lead to inconsistent results. Posteriori approach derives a dietary pattern independently of the existing nutrition-disease knowledge. It showed a dietary pattern abundant with plant-based food, oily fish, lower consumption of processed food, saturated fat, and simple sugar which appears to be beneficial to cognitive health. Despite inconclusive evidence from both approaches, diet and exercise, beneficial for other diseases, remains to be the two key modifiable factors for cognitive function. Large-scale prospective studies in multiethics population are required to provide stronger evidence in the future., (© 2014 Elsevier Inc. All rights reserved.)

Objectives: To test the individual effect of artificial food colorings (AFCs) and a preservative on the behavior of the general Chinese population., Method: One hundred thirty children (70 boys and 60 girls) in Hong Kong with a mean age of 8.64 years were enlisted to the study with a within-subject crossover between AFCs, a preservative (sodium benzoate), and a placebo capsule. Two behavior scores were used including the strengths and weaknesses of attention deficit hyperactivity disorder and normal behavior rating scale and the child behavior checklist-teacher report form., Results: Capsule A containing AFCs and Capsule B containing sodium benzoate had no significant adverse effect compared with placebo in both behavior scores. This result persisted when analysis was restricted to children with 85% consumption of capsule (per protocol analysis)., Conclusion: There seem to be no significant associations between AFCs and a preservative on Chinese children's behavior at the age of 8 to 9 years. Future directions and implications of this research are discussed.

Background & Aims: Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD., Methods: This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy., Results: 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; p<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (p<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (p<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome., Conclusions: The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: Exploratory research findings have suggested that otoacoustic emission (OAE) recordings may be predictive for infants at risk of sudden infant death syndrome (SIDS). The present study aimed to investigate whether an actual SIDS prevalence rate was comparable to OAE-determined rates for "at risk" status., Methods: Previously collected OAE results from 521 infants in Hong Kong were used for analyses and OAE-determined "at risk" rate compared to the prevalence rate for SIDS in Hong Kong infants., Results: Results indicated that the OAE-determined rates were very much greater than the actual prevalence of SIDS in Hong Kong., Conclusion: The use of OAE screening to identify infants at risk for SIDS is therefore not advisable, using present criteria, as false alarm rates would be very high and this may cause unnecessary parental anxiety and a considerable additional burden to the health care system., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Endoscopic injection of N-Butyl-2-cyanoacrylate is a widely accepted treatment for esophagogastric varices. This procedure is commonly associated with minor complications which include transient pyrexia and abdominal discomfort. Serious vascular complications secondary to systemic embolization of cyanoacrylate have rarely been reported. We describe the CT findings of extensive splenic infarction in a patient following cyanoacrylate injection for gastric varices.

Objective: Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population., Methods: Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively., Results: Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54)., Conclusion: NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.

According to the International Classification of Functioning, Disability and Health model endorsed by the World Health Organization, participation in everyday activities is integral to normal child development. However, little is known about the influence of motor ability and weight status on physical activity participation in children with developmental coordination disorder (DCD). This study aimed to (1) compare motor performance, weight status and pattern of out-of-school activity participation between children with DCD and those without; and (2) identify whether motor ability and weight status were determinants of participation patterns among children with DCD. We enrolled 81 children with DCD (boys, n = 63; girls, n = 18; mean age, 8.07 ± 1.5 years) and 67 typically developing children (boys, n = 48; girls, n = 19; mean age, 8.25 ± 1.6 years). Participation patterns (diversity, intensity, companionship, location, and enjoyment) were evaluated with the Children Assessment of Participation and Enjoyment. Motor ability was evaluated with the Movement Assessment Battery for Children, second edition (MABC-2). Other factors that may influence participation such as age, gender, and body weight were also recorded. Analysis of variance was used to compare outcome variables of the two groups, and significant determinants of activity participation were identified by multiple regression analysis. Children with DCD participated in fewer activities (i.e., limited participation diversity) and participated less frequently (i.e., limited participation intensity) than their typically developing peers; however, companionship, location of participation, and enjoyment level did not differ between the two groups. Children in the DCD group demonstrated significantly worse motor ability as assessed by the MABC-2. Further, a greater proportion of children in the DCD group were in the overweight/obese category compared with their typically developing peers. After accounting for the effects of age and gender, motor ability and weight category explained 7.6% and 5.0% of the variance in participation diversity, respectively, for children with DCD. Children with DCD showed less diverse and less intense out-of-school activity participation than typically developing children. Motor impairment and weight status were independently associated with the lower participation diversity. Interventions aiming at improving participation for children with DCD should target weight control and training in motor proficiency. Further study is needed to identify other factors that may hinder participation in this group of children., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A 62 year-old woman who presented with an atraumatic acute abdomen was discovered to have haemoperitoneum with splenic rupture on urgent computed tomography and was immediately referred for life-saving emergency splenectomy. Histopathological examination revealed secondary splenic amyloidosis. The patient was later found to be suffering from infective endocarditis secondary to her permanent cardiac pacemaker. This report describes a patient who could have suffered from a long-standing infected vegetation on a permanent cardiac pacemaker, which led to splenic amyloidosis and spontaneous splenic rupture.

Conventional dietary recommendation for obesity management is a low-fat energy-restricted diet, which however, only have modest and non-sustained effects on weight reduction. Alternative dietary interventions, including low-glycemic index (GI) diet, have been proposed. Glycemic index is a measure of blood glucose excursion per unit of carbohydrate. Foods with high GI are rapidly digested, absorbed and transformed into glucose. These processes cause accelerated and transient surges in blood glucose and insulin, earlier return of hunger sensation and excessive caloric intake. Conversely, low-GI diet decreases blood glucose and insulin excursion, promotes greater fat oxidation, decreases lipogenesis and increases satiety. Modern food-processing technology has produced many food products with high GI which may contribute to the burgeoning epidemic of obesity especially in children/adolescents. Epidemiological and clinical trials suggest a role for low-GI diet in the management of childhood obesity and associated cardio-metabolic risks although results are not always consistent. In this article, we shall review the physiological basis and current evidence for and against low-GI diet in obesity management, with particular focus in children and adolescents., (© 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.)

Obesity is a public health problem that has become epidemic worldwide. Substantial literature has emerged to show that overweight and obesity are major causes of co-morbidities, including type II diabetes, cardiovascular diseases, various cancers and other health problems, which can lead to further morbidity and mortality. The related health care costs are also substantial. Therefore, a public health approach to develop population-based strategies for the prevention of excess weight gain is of great importance. However, public health intervention programs have had limited success in tackling the rising prevalence of obesity. This paper reviews the definition of overweight and obesity and the variations with age and ethnicity; health consequences and factors contributing to the development of obesity; and critically reviews the effectiveness of current public health strategies for risk factor reduction and obesity prevention.

Information concerning the nature of nutritionist-patient relationships is very limited. This qualitative and quantitative study examined nutritionist's skills, attributes, and beliefs towards nutrition counseling during a lifestyle modification intervention program, and whether this affected the patient's weight outcome. 24 nutrition consultations were observed during the program and the nutritionists were interviewed for their perception on practice (n = 4). A statistically significant difference was observed between the nutritionists in regard to patient's weight change after adjustment for age and baseline weight (p < 0.001). Key nutritionist skills identified that influenced weight outcome were meticulous investigation of the underlying obesity cause, identification of the subject's stage of change, and psychological support.

There is little information about how clients attending lifestyle modification programs view the outcomes. This qualitative study examined the clients' experience of a community based lifestyle modification program in Hong Kong. Semi-structured interviews were conducted with 25 clients attending the program. Clients perceived the program had positive impacts on their health and nutrition knowledge. They experienced frustration, negative emotion, lack of motivation, and pressure from others during the program. Working environment and lack of healthy food choices in restaurants were the major perceived environmental barriers for lifestyle modification. Clients valued nutritionists' capability of providing professional information and psychological support in the program. Our results suggest that nutritionist's capability of providing quality consultations and patient-centered care are important for empowering clients achieve lifestyle modification.

Background/objectives: To examine the daily intake of bone health-related nutrients and to explore the association between diet composition and estimated net endogenous acid production (estimated NEAP) in Hong Kong Chinese adolescents., Subject/methods: In total, 171 boys and 180 girls aged 10-12 years of Chinese origin from nine primary schools from the Hong Kong Adolescent Bone Health Cohort Study. The study design used food frequency questionnaire. Mean daily intakes of foods and selected nutrients were estimated. Mean percentage of nutrient intake contributed by different food groups was presented. Frassetto's method was used to calculate the estimated NEAP from the diet's protein to potassium ratio., Results: There was no significant difference in the energy-adjusted intakes of most nutrients between boys and girls, except for intakes of vitamins C and D. Mean protein, sodium and potassium intakes were higher than the Chinese dietary reference intake (DRI), whereas mean intakes of magnesium, calcium and vitamin D were lower than the DRI. Boys had significantly higher estimated NEAP than girls (P=0.0051). Estimated NEAP was significantly positively correlated with meat intake and negatively associated with the consumption of fruits, vegetables, legumes, beverages and dairy products., Conclusions: The results highlight the importance of considering whole diet quality when interpreting the effects of single nutrient or diet's net acid load on bone. The effect on high protein intake and low fruit and vegetable intake on the long-term bone health of Hong Kong Chinese adolescents warrants attention.

Objectives: We sought to evaluate the impact of a strategy of reduced-dose fibrinolytic acceleration of ST-segment elevation myocardial infarction (STEMI) treatment followed by urgent percutaneous coronary intervention (FAST-PCI) on the mortality, reinfarction, and stroke rates in STEMI patients as compared with a primary percutaneous coronary intervention (PPCI) approach., Background: Time to reperfusion is a major determinant of mortality among STEMI patients. Rapid initiation of fibrinolytic therapy can shorten time to reperfusion, and mechanical therapy of the culprit lesion is known to be beneficial., Methods: Data from 2,869 STEMI patients treated in 5 high-volume percutaneous coronary intervention (PCI) centers were pooled for analysis. Mortality at 30 days was the primary end point. Death, reinfarction, and stroke were secondary end points, as were infarct-related artery TIMI (Thrombolysis In Myocardial Infarction) flow grade before PCI and shock on arrival to the catheterization laboratory., Results: Compared to PPCI, mortality at 30 days was significantly lower with FAST-PCI (3.8% vs. 6.4%, p = 0.002). The combined triple end point of death, reinfarction, or stroke was also less frequent (5.1% vs. 8.9%, p < 0.0001). The FAST-PCI patients had a lower incidence of Killip class IV (5.6% vs. 10.9%, p < 0.0001) and higher infarct-related artery TIMI flow grades (2.1 +/- 1.2 vs. 1.1 +/- 1.3, p < 0.0001) upon arrival in the catheterization laboratory. Stepwise logistic regression analysis demonstrated that FAST-PCI was an independent predictor of 30-day mortality (relative risk = 0.542, p = 0.0151)., Conclusions: The FAST-PCI strategy reduced the mortality and combined end point of death, reinfarction, and stroke among STEMI patients, without increasing the risk of stroke or bleeding, compared to PPCI. Fibrinolysis before hospital admission also increased the initial infarct-related artery patency and decreased the likelihood of shock at presentation.

Percutaneous intervention in saphenous vein grafts (SVG) carries a higher risk of distal embolization than intervention in a native vessel, and use of a distal protection device has been shown to improve the outcomes in SVG interventions. We describe an intervention done in an unexpected 'Y' SVG which required dual distal protection with Filterwires placed in both limbs of the diseased graft and which was performed via a 6 Fr guide catheter., ((c) 2007 Wiley-Liss, Inc.)

Purpose: To describe the anesthetic management of Cesarean delivery in a patient with hypoplastic anemia and severe pre-eclampsia., Clinical Features: A 28-yr-old parturient with a history of thrombocytopenia was admitted with signs of pre-eclampsia (blood pressure of 140/90 mmHg, heavy proteinuria and moderate bilateral ankle edema) at 25 weeks of gestation. Laboratory studies revealed pancy-topenia (hemoglobin 6.4 g.dL(-1), white cell count 3.43 x 10(9).L(-1), platelet count 20 x 10(9).L(-1)) and bone marrow biopsy showed hypoplastic anemia. As pre-eclampsia worsened, a Cesarean delivery was performed at 27 weeks with prophylactic platelet transfusion and meticulous blood pressure control. The procedure was uneventful, conducted under general anesthesia with an estimated blood loss of around 600 mL and a live female baby was delivered. Postoperatively her blood pressure and neurological symptoms improved but thrombocytopenia remained at discharge., Conclusions: Hypoplastic anemia is rare in pregnancy but it poses an increased risk for both mother and fetus. The mother is at risk of life-threatening episodes of bleeding and infection and a multidisciplinary team approach (obstetrician, anesthesiologist, hematologist and pediatrician) is essential. An accurate assessment of the hematological condition should be made and abnormalities corrected before surgery. Regional anesthesia may not be possible in this circumstance.

A 2-year-old child with a ventriculoperitoneal shunt and a shunt revision 18 months previously developed a shunt infection. A CT scan of the abdomen was performed soon after the shunt catheter was removed. A peculiar invagination in the liver was demonstrated along the same course of a recently removed intraperitoneal catheter, presumably caused by the catheter. There have been no reported cases of deformity and pseudo-fissure of the liver, which may mimic pathologic processes on ultrasound or CT, caused by a ventriculoperitoneal shunt.

Homotropic cooperativity in Escherichia coli aspartate transcarbamoylase results from the substrate-induced transition from the T to the R state. These two alternate states are stabilized by a series of interdomain and intersubunit interactions. The salt link between Lys-143 of the regulatory chain and Asp-236 of the catalytic chain is only observed in the T state. When Asp-236 is replaced by alanine the resulting enzyme exhibits full activity, enhanced affinity for aspartate, no cooperativity, and no heterotropic interactions. These characteristics are consistent with an enzyme locked in the functional R state. Using small angle x-ray scattering, the structural consequences of the D236A mutant were characterized. The unliganded D236A holoenzyme appears to be in a new structural state that is neither T, R, nor a mixture of T and R states. The structure of the native D236A holoenzyme is similar to that previously reported for another mutant holoenzyme (E239Q) that also lacks intersubunit interactions. A hybrid version of aspartate transcarbamoylase in which one catalytic subunit was wild-type and the other had the D236A mutation was also investigated. The hybrid holoenzyme, with three of the six possible interactions involving Asp-236, exhibited homotropic cooperativity, and heterotropic interactions consistent with an enzyme with both T and R functional states. Small angle x-ray scattering analysis of the unligated hybrid indicated that the enzyme was in a new structural state more similar to the T than to the R state of the wild-type enzyme. These data suggest that three of the six intersubunit interactions involving D236A are sufficient to stabilize a T-like state of the enzyme and allow for an allosteric transition.

A hybrid version of Escherichia coli aspartate transcarbamoylase was investigated in which one catalytic subunit has the wild-type sequence, and the other catalytic subunit has Glu-239 replaced by Gln. Since Glu-239 is involved in intersubunit interactions, this hybrid could be used to evaluate the extent to which T state stabilization is required for homotropic cooperativity and for heterotropic effects. Reconstitution of the hybrid holoenzyme (two different catalytic subunits with three wild-type regulatory subunits) was followed by separation of the mixture by anion-exchange chromatography. To make possible the resolution of the three holoenzyme species formed by the reconstitution, the charge of one of the catalytic subunits was altered by the addition of six aspartic acid residues to the C terminus of each of the catalytic chains (AT-C catalytic subunit). Control experiments indicated that the AT-C catalytic subunit as well as the holoenzyme formed with AT-C and wild-type regulatory subunits had essentially the same homotropic and heterotropic properties as the native catalytic subunit and holoenzyme, indicating that the addition of the aspartate tail did not influence the function of either enzyme. The control reconstituted holoenzyme, in which both catalytic subunits have Glu-239 replaced by Gln, exhibited no cooperativity, an enhanced affinity for aspartate, and essentially no heterotropic response identical to the enzyme isolated without reconstitution. The hybrid containing one normal and one mutant catalytic subunit exhibited homotropic cooperativity with a Hill coefficient of 1.4 and responded to the nucleotide effectors at about 50% of the level of the wild-type enzyme. Small angle x-ray scattering experiments with the hybrid enzyme indicated that in the absence of ligands it was structurally similar, but not identical, to the T state of the wild-type enzyme. In contrast to the wild-type enzyme, addition of carbamoyl phosphate induced a significant alteration in the scattering pattern, whereas the bisubstrate analog N-phosphonoacetyl-L-aspartate induced a significant change in the scattering pattern indicating the transition to the R-structural state. These data indicate that in the hybrid enzyme only three of the usual six interchain interactions involving Glu-239 are sufficient to stabilize the enzyme in a low affinity, low activity state and allow an allosteric transition to occur.

In recent years, there has been extraordinary progress in understanding the cellular and molecular cascades that mediate neuron death following necrotic insults. With this knowledge has come the recognition of ways in which these cascades can be modulated by extrinsic factors, altering the likelihood of subsequent neuron death. In this review, we consider the ability of a variety of hormones to modulate necrotic death cascades. Specifically, we will examine the ability of the stress hormones glucocorticoids and corticotropin-releasing factor, of thyroid hormone, and of pre-ischemic exposure to catecholamines to augment necrotic neuron death. In contrast, estrogen, insulin and postischemic exposure to catecholamines appear to decrease necrotic neuron death. We review the heterogeneous mechanisms that are likely to mediate these hormone effects, some possible clinical implications and the therapeutic potentials of these findings.

Corneal thickness changes were measured after bathing the outer corneal surface with sodium chloride solutions of various concentrations. Bathing was accomplished by total immersion in the solution in a goggle or by the application of drops for a period of 20 minutes. A nearly linear relationship was found between hypotonicity and the degree of corneal swelling.