Artificial intelligence for detection of intracranial haemorrhage on head computed tomography scans: diagnostic accuracy in Hong Kong.

INTRODUCTION: The use of artificial intelligence (AI) to identify acute intracranial haemorrhage (ICH) on computed tomography (CT) scans may facilitate initial imaging interpretation in the accident and emergency department. However, AI model construction requires a large amount of annotated data for training, and validation with real-world data has been limited. We developed an algorithm using an open-access dataset of CT slices, then assessed its utility in clinical practice by validating its performance on CT scans from our institution. METHODS: Using a publicly available international dataset of >750 000 expert-labelled CT slices, we developed an AI model which determines ICH probability for each CT scan and nominates five potential ICH-positive CT slices for review. We validated the model using retrospective data from 1372 non-contrast head CT scans (84 [6.1%] with ICH) collected at our institution. RESULTS: The model achieved an area under the curve of 0.842 (95% confidence interval=0.791-0.894; P<0.001) for scan-based detection of ICH. A pre-specified probability threshold of ≥50% for the presence of ICH yielded 78.6% accuracy, 73% sensitivity, 79% specificity, 18.6% positive predictive value, and 97.8% negative predictive value. There were 62 true-positive scans and 22 false-negative scans, which could be reduced to six false-negative scans by manual review of model-nominated CT slices. CONCLUSION: Our model exhibited good accuracy in the CT scan-based detection of ICH, considering the low prevalence of ICH in Hong Kong. Model refinement to allow direct localisation of ICH will facilitate the use of AI solutions in clinical practice.

CT analysis of the posterior anatomical landmarks of the scoliotic spine.

AIM: To use computed tomography (CT) to assess the validity and reliability of the posterior landmarks, spinous processes (SP), transverse processes (TP), and centre of lamina (COL), as compared to the Cobb angle to assess the curve severity and progression of adolescent idiopathic scoliosis (AIS). MATERIALS AND METHODS: A consecutive series of CT examinations of severe AIS patients were included retrospectively. SP, TP, and COL angles were measured for all curves and compared to the Cobb angle. RESULTS: One hundred and five patients were included. The mean Cobb versus SP, TP, and COL angles were, 54° versus 37°, 49°, and 51° in the thoracic curves and 34° versus 26°, 31°, and 34° in the (thoraco)lumbar curves. Intraclass correlation coefficient values for intra-rater measurements of the SP, TP, and COL angles were 0.93, 0.97, and 0.95 and 0.70, 0.90, and 0.88 for inter-rater measurements. The correlations between the Cobb angle and SP, TP, and COL angles in thoracic and (thoraco)lumbar curves were 0.79 and 0.66, 0.87 and 0.84, and 0.80 and 0.70. CONCLUSIONS: The posterior spinal landmarks can be used for assessment of scoliosis severity in AIS; however, they show a systematic underestimation, but a strong correlation with the coronal Cobb angle. TP and COL angles had the highest validity.

The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Sequential spine-hand radiography for assessing skeletal maturity with low radiation EOS imaging system for bracing treatment recommendation in adolescent idiopathic scoliosis: a feasibility and validity study.

PURPOSE: The EOS-imaging system is increasingly adopted for clinical follow-up in scoliosis with the advantages of simultaneous biplanar imaging of the spine in an erect position. Skeletal maturity assessment using a hand radiograph is an essential adjunct to spinal radiography in scoliosis follow-up. This study aims at testing the feasibility and validity of a newly proposed EOS workflow with sequential spine-hand radiography for skeletal maturity assessment and bracing recommendation. METHODS: EOS spine-hand radiographs from patients with diagnosis of idiopathic scoliosis, including both sexes and an age range of ten to 14 years, were scored using the Thumb Ossification Composite Index (TOCI), Sanders and Risser methods. Intraclass correlation coefficients (ICCs) were calculated for inter/intraobserver agreement and were tested with Cronbach's alpha values. RESULTS: In all, 60 EOS-spine hand radiographs selected from subjects with diagnosis of adolescent idiopathic scoliosis (AIS), including 32 male patients (mean age 11.53 years; 10 to 14) and 28 female patients (mean age 11.50 years; 10 to 13) who underwent sequential spine-hand low dose EOS imaging were generated for analysis. The overall interobserver (ICC = 0.997) and intraobserver agreement (α > 0.9) demonstrated excellent agreement for TOCI staging; ICC > 0.994 for both TOCI and Sanders staging comparing traditional digital versus EOS hand radiography; ICC ≥ 0.841 for agreement on bracing recommendation among TOCI versus the Risser and Sanders system. CONCLUSION: With the proposed new EOS workflow it was feasible to produce high image quality for skeletal maturity assessment with excellent reliability and validity to inform consistent bracing recommendation in AIS. The workflow is applicable for busy daily clinic settings in tertiary scoliosis centres with reduced time cost, improved efficiency and throughput of the radiology department. LEVEL OF EVIDENCE: III.

Molecular and clinical characterization of citrin deficiency in a cohort of Chinese patients in Hong Kong.

BACKGROUND AND OBJECTIVES: This retrospective study analysed a case series of subjects with citrin deficiency, and aims to present the molecular and clinical characterization of this disease in the Hong Kong Chinese population for the first time. PATIENTS AND METHODS: Data from medical records of eighteen patients with citrin deficiency (years 2006-2015) were retrieved. Demographic data, biochemical parameters, radiological results, genetic testing results, management, and clinical outcome were collected and analysed. RESULTS: Eighteen patients with diagnosis of citrin deficiency were recruited. All 18 patients carried at least one common pathogenic variant c.852_855delTATG in SLC25A13. Prolonged jaundice (neonatal intrahepatic cholestasis caused by citrin deficiency, NICCD) was the most common presenting symptom, in conjunction with elevated plasma citrulline, threonine, alkaline phosphatase, and alpha-fetoprotein levels. The abnormal biochemical parameters including liver derangement returned to normal range in most of the cases by 6 months of age after the introduction of a lactose-free formula. There were a few cases with atypical presentations. Two subjects did not present with NICCD, and were subsequently diagnosed later in life after their siblings presented with symptoms of citrin deficiency at one month of age and subsequently received a molecular diagnosis. One patient with citrin deficiency also exhibited multiple liver hemangioendotheliomas, which subsided gradually after introduction of a lactose-free formula. Only one patient from this cohort was offered expanded metabolic screening at birth. She was not ascertained by conducted newborn screening and was diagnosed upon presentation with cholestatic jaundice by 1 month of age. CONCLUSION: This is the first report of the clinical and molecular characterization of a large cohort of patients with citrin deficiency in Hong Kong. The presentation of this cohort of patients expands the clinical phenotypic spectrum of NICCD. Benign liver tumors such as hemangioendotheliomas may be associated with citrin deficiency in addition to the well-known association with hepatocellular carcinoma. Citrin deficiency may manifest in later infancy period with an NICCD-like phenotype. Furthermore, this condition is not always ascertained by expanded newborn metabolic screening testing.

Altered White Matter Microstructure in the Corpus Callosum and Its Cerebral Interhemispheric Tracts in Adolescent Idiopathic Scoliosis: Diffusion Tensor Imaging Analysis.

BACKGROUND AND PURPOSE: Neural system was one of the important contributors to the etiopathogenesis of adolescent idiopathic scoliosis; additionally, the morphology of corpus callosum interconnecting both hemispheres of the brain was found to be altered morphologically. Our aim was to evaluate and compare the microstructural changes of the corpus callosum and its interhemispheric white matter fiber tracts interconnecting both cerebral hemispheres in patients with adolescent idiopathic scoliosis and matched controls using diffusion tensor imaging. MATERIALS AND METHODS: Brain DTI was performed in 69 patients with adolescent idiopathic scoliosis (female, right thoracic/thoracolumbar curve) and 40 age-matched controls without adolescent idiopathic scoliosis (female). 2D and 3D segmentation of the corpus callosum were performed using a region-growing method, and the corpus callosum was further divided into 6 regions, including the rostrum, genu, anterior and posterior midbodies, isthmus, and splenium. The laterality index was calculated to quantify the asymmetry of the corpus callosum. Interhemispheric fiber tractography were performed using the Brodmann atlas. RESULTS: 2D ROI analysis revealed reduced fractional anisotropy in the genu and splenium (P = .075 and P = .024, respectively). Consistently reduced fractional anisotropy on the left sides of the genu and splenium was also found in 3D ROI analysis (P = .03 and P = .012, respectively). The laterality index analysis revealed a pseudo-right lateralization of the corpus callosum in adolescent idiopathic scoliosis. Interhemispheric fibers via the splenium interconnecting Brodmann 3, 1, and 2; Brodmann 17; and Brodmann 18 (corresponding to the primary somatosensory cortex and primary and secondary visual cortices) were also found to have reduced fractional anisotropy (P ≤ .05). CONCLUSIONS: Reduced fractional anisotropy was found in the genu and splenium of the corpus callosum and corresponding interhemispheric fiber tracts interconnecting the somatosensory and visual cortices via the splenium. Our results are suggestive of altered white matter microstructure within the brain of those with adolescent idiopathic scoliosis, which could be related to abnormal brain maturation during adolescence in adolescent idiopathic scoliosis and could possibly explain the previously documented somatosensory function impairment and visuo-oculomotor dysfunction in this condition.

Dietitian-led lifestyle modification programme for obese Chinese adolescents with non-alcoholic fatty liver disease: a randomized controlled study.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is increasing. This study evaluated the efficacy of a dietitian-led lifestyle modification programme (D-LMP) to reduce NAFLD in obese adolescents. METHODS: Subjects with intra-hepatic triglyceride content (IHTC) equal to or greater than 5% diagnosed by proton-magnetic resonance spectroscopy (1H-MRS) were enroled and randomly assigned to either the D-LMP intervention or conventional paediatrician-led consultation (P-CON) group. Subjects in the P-CON group received usual care consisting of a consultation by a paediatrician with the child and parents every 16 weeks. Intention-to-treat analysis was used for data analysis. RESULTS: Fifty-two subjects were recruited, with 26 in each group. After the initiation phase (at week-16), there was a greater difference in the change in the IHTC and BMI z-score in the D-LMP group (P = 0.029 and <0.001, respectively) and there was a decrease in dietary intake of fat content (P = 0.019). After 52 weeks of the maintenance phase, both groups had reductions of IHTC to 2-3% and there was no intergroup difference in the rate of reduction. During the maintenance phase, parents' involvement was minimal in the D-LMP group, with only three parents accompanying their children to attend the dietitian sessions. In contrast, over 90% of the parents in the P-CON group regularly accompanied their children to attend the consultations suggesting the possibility that regular parental and paediatrician involvement may contribute to increasing awareness on fatty liver complications. Multivariate analysis showed that only reduction in body fat remained as an independent factor associated with remission of NAFLD at the end of both study phases. CONCLUSIONS: A dietitian-led lifestyle modification intervention reduced IHTC, BMI z-score and body fat in obese Chinese adolescents with NAFLD. To sustain the effect of this intervention, regular parental and paediatrician involvement may be important.

Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

OBJECTIVE: Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. METHODS: In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 µg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. RESULTS: Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. CONCLUSION: This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy.

Liver fibrosis and fatty liver in Asian HIV-infected patients.

BACKGROUND: Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM: To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS: Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS: All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. CONCLUSIONS: HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.

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.

Variation in anisotropy and diffusivity along the medulla oblongata and the whole spinal cord in adolescent idiopathic scoliosis: a pilot study using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Disturbed somatosensory evoked potentials have been demonstrated in patients with adolescent idiopathic scoliosis (but this functional delay was found to originate above the C5-6 level, while the lower cord level was unaffected). Together with MR imaging observation of tonsillar ectopia and a relatively tethered cord, we hypothesized that there is disturbed mean diffusivity integrity along the spinal cord. In this study, advanced DTI was used to evaluate whether there was underlying decreased WM integrity within the brain stem and spinal cord in adolescent idiopathic scoliosis and any relationship to cerebellar tonsillar ectopia. Clinical impact on balance testing was also correlated. MATERIALS AND METHODS: Thirteen girls with adolescent idiopathic scoliosis with right thoracic curves were compared with 13 age-matched healthy girls. DTI of the brain and whole spinal cord was performed. ROIs were manually defined for the medulla oblongata and along each intervertebral segment of the cord. Mean values of fractional anisotropy and mean diffusivity were computed at the defined regions. Between-group comparisons were performed by 1-way ANOVA. RESULTS: Significantly decreased fractional anisotropy values and increased mean diffusivity values were found at the medulla oblongata and C1-2, C2-3, C3-4, and C4-5 segments in patients with adolescent idiopathic scoliosis compared with healthy subjects. No significant difference was found in the lower cord levels. Significant correlation was found between the tonsillar level and fractional anisotropy value at the C4-5 level in patients with adolescent idiopathic scoliosis only. CONCLUSIONS: The findings from this study are in agreement with previous findings showing abnormal somatosensory evoked potential readings occurring only above the C5-6 level in patients with adolescent idiopathic scoliosis; these findings might partially explain the pathophysiology of the neural pathway involved.

PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome.

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.

Saturation of the free carrier absorption in ZnTe crystals.

This study systematically investigates the influence of free carriers on the generation of THz in ZnTe crystals, over a wide range of pumping fluences. As the pumping fluence is increased (< 6.36 mJ/cm(2)), the concentration of free carriers gradually increases and the THz output power is saturated, as clearly demonstrated by the time delay in the THz temporal waveforms, the changes in the THz spectral weight and the red-shift in the PL spectra. For high pumping fluences (> 6.36 mJ/cm(2)), spectacularly, there is a significant quadratic increase in the THz output power when the pumping fluence is increased, as well as at low pumping fluences of < 0.58 mJ/cm(2), because of the saturation of free carriers.

Molecular cloning, homology modeling and site-directed mutagenesis of vanadium-dependent bromoperoxidase (GcVBPO1) from Gracilaria changii (Rhodophyta).

Vanadium-dependent haloperoxidases belong to a class of vanadium enzymes that may have potential industrial and pharmaceutical applications due to their high stability. In this study, the 5'-flanking genomic sequence and complete reading frame encoding vanadium-dependent bromoperoxidase (GcVBPO1) was cloned from the red seaweed, Fracilaria changii, and the recombinant protein was biochemically characterized. The deduced amino acid sequence of GcVBPO1 is 1818 nucleotides in length, sharing 49% identity with the vanadium-dependent bromoperoxidases from Corralina officinalis and Cor. pilulifera, respectively. The amino acid residues associated with the binding site of vanadate cofactor were found to be conserved. The Km value of recombinant GcVBPO1 for Br(-) was 4.69 mM, while its Vmax was 10.61 µkat mg(-1) at pH 7. Substitution of Arg(379) with His(379) in the recombinant protein caused a lower affinity for Br(-), while substitution of Arg(379) with Phe(379) not only increased its affinity for Br(-) but also enabled the mutant enzyme to oxidize Cl(-). The mutant Arg(379)Phe was also found to have a lower affinity for I(-), as compared to the wild-type GcVBPO1 and mutant Arg(379)His. In addition, the Arg(379)Phe mutant has a slightly higher affinity for H2O2 compared to the wild-type GcVBPO1. Multiple cis-acting regulatory elements associated with light response, hormone signaling, and meristem expression were detected at the 5'-flanking genomic sequence of GcVBPO1. The transcript abundance of GcVBPO1 was relatively higher in seaweed samples treated with 50 parts per thousand (ppt) artificial seawater (ASW) compared to those treated in 10 and 30 ppt ASW, in support of its role in the abiotic stress response of seaweed.

Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers.

BACKGROUND: The diagnosis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non-invasive assessments are urgently needed. AIM: To evaluate cell apoptotic marker cytokeratin-18 M30 and total cell death markers cytokeratin-18 M65/M65ED for the assessment and monitoring of NAFLD. METHODS: A cohort of 147 patients with biopsy-proven NAFLD and 73 controls were enrolled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS: M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non-NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver-operating characteristics curve above 0.8 in predicting disease progression. At cut-off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression. CONCLUSIONS: Cytokeratin-18 M30 and M65/M65ED have moderate accuracy in detecting non-alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.