Factors predicting screen time related to physical and behavioural complaints in primary school children.

BACKGROUND AND OBJECTIVE: Physical and behavioural problems from extended usage of electronic devices are issues among primary school children. This study is aimed to investigate the prevalence of physical and behavioural complaints arising from the electronic device usage and to identify the potential factors that predicted the complaints. METHODS: This was a primary school-based cross-sectional study using multistage cluster sampling, conducted at Bau district in Sarawak, Malaysia in 40 primary schools. A questionnaire was used to collect information of usage pattern in insufficient lighting, timing and position. The physical and behavioural complaints were traced. Data analysis was performed using SPSS version 22. A p-value < 0.05 with 95% CI was considered as statistically significant. RESULTS: About 52.8% of the 569 students used digital devices in a bright room, 69.8% in the day time and 54.4% in sitting position. The physical complaints were headache (32.9%), neck, shoulder and back pain (32.9%) followed by by eye strain (31.8%). Regarding behavioural problems, 25.7% of the students had loss of interest in study and outdoor activities (20.7%), skipped meals (19.0%) and arguments/disagreements with parents (17.9%). After logistic regression analysis, the lying position (OR=1.71, 95% CI: 1.096, 2.688) and darkroom lighting (OR=2.323 95% CI: 1.138, 4.744) appeared to be potential predictors of the complaint. CONCLUSION: One-quarter of the students studied experienced physical complaints, and one-fifth had behavioural problems associated with the use of electronic devices. Lying position and darkroom lighting are the potential predictors of complaints. Therefore, we suggest that the children should use electronic devices in the sitting position with adequate room lighting.

Visit-to-visit systolic blood pressure variability predicts all-cause and cardiovascular mortality after lacunar infarct.

BACKGROUND AND PURPOSE: Both blood pressure (BP) and its variability (BPV) are established risk factors for development of atherosclerotic disease and are associated with an increased risk for cardiovascular and all-cause mortality. The prognostic implications of outpatient clinic visit-to-visit BPV amongst patients with lacunar infarction are nevertheless unknown. METHODS: The clinical outcome of 281 patients with lacunar infarction was prospectively followed up. The average BP and BPV, as determined by the standard deviation of the systolic and diastolic BP, were recorded during a mean 13 ± 6 outpatient clinic visits. RESULTS: The mean age of the population was 70 ± 10 years. After a mean 78 ± 18 months follow-up, 65 patients died (23%), 31% (20/65) due to cardiovascular causes; 14% and 7% developed recurrent stroke and acute coronary syndrome. After adjusting for age, sex, mean systolic and diastolic BP, cardiovascular risk factors and comorbidities, patients with a systolic BPV of the third tertile had significantly higher risk of all-cause mortality [hazard ratio (HR) 1.97, 95% confidence interval (CI) 1.02-3.80, P = 0.04) and cardiovascular mortality (HR 7.64, 95% CI 1.65-35.41, P < 0.01) than those with systolic BPV of the first tertile. Nevertheless, systolic BPV did not predict recurrent stroke or acute coronary syndrome. Diastolic BPV did not predict various adverse clinical outcomes. CONCLUSIONS: Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality after lacunar infarct, independent of conventional risk factors including average BP control.

Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family.

Autosomal dominant spinocerebellar ataxias (SCA) constitute a heterogeneous group of inherited disorders. The transglutaminase 6 (TGM6) gene was recently suggested as a SCA causative gene in Chinese SCA families. In this study, two affected members of a three-generation Chinese family with SCA characterized by progressive cerebellar ataxia and lower limb pyramidal signs were subjected to whole exome sequencing. Through bioinformatics analysis of the sequence variants in these two individuals, we identified a novel mutation in the TGM6 gene (c.1528G>C) which showed perfect co-segregation with disease phenotype in all nine members of this family. This finding confirms that mutations in TGM6 gene represent an important cause of SCA in Chinese. This study also shows that whole exome sequencing of a small number of affected individuals, leveraged on bioinformatics analysis, can be an efficient strategy for identifying causative mutations in rare Mendelian disorders.

Detection of endocrine disruptors - from simple assays to whole genome scanning.

Endocrine disruptors frequently bear little structural relationship to the hormone whose actions they disrupt. Consequently, the threat of an uninvestigated chemical cannot easily be assessed. Here three different approaches to assessment are discussed. The first presumes an endocrine-disrupting property, following which a cell model capable of responding to such a hormone is used. Although simple and cheap, it provides limited data. A second approach involves multiple assays to detect multiple hormones. Increasing the amount of data increased the difficulty in assessing the significance of results. To meet this problem, cluster analysis based on a simple mathematical matrix was adopted. The matrix was used to determine (i) a limited number of assays to identify a maximum number of endocrine disruptors and (ii) the chemicals with the most wide-ranging effects. A third approach was a whole genome expression analysis based on expression of mRNAs in human TE671 medulloblastoma cells. Expression of individual mRNAs was assessed using the Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 chip. The significance of differential expressed genes was assessed based on gene ontology and pathways analyses using DAVID and GenMaPP programs. The results illustrated the very wide-ranging effects of these chemicals across the genome.

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong.

This study aims to evaluate genotyping assays for hepatitis C virus (HCV). An in-house nucleic acid sequencing method is performed in parallel with the Roche Linear Array HCV genotyping test on 73 HCV-positive (66 clinical samples and seven proficiency testing quality control samples) and 12 HCV-negative samples (11 clinical samples and one proficiency testing sample). The performance of the in-house method was comparable with that of the Roche assay (concordance rate: 89.4%). Discordant results included four mixed infections missed by the in-house method, two false-negatives with the Roche assay, and three discrepant results. The in-house method exhibited a higher resolution (subtype vs. genotype level) at a lower running cost (25% of the commercial assay). The in-house method was also used to genotype 375 HCV clinical isolates to determine the genotypic distribution of HCV in Hong Kong between 2005 and 2008. A total of 441 (52.8%) clinical isolates proved to be genotype 1, which shows a poorer response to interferon therapy. Genotype 6 was the next most common (32.0%). Prevalence of genotypes 2 and 3 was 7.7% and 6.6%, respectively, and prevalence of genotypes 4 and 5 was 0.9% and 0%, respectively. Although the in-house nucleic acid sequencing method failed to detect a few cases of mixed HCV infection, its high resolution and low running cost make it suitable for surveillance and outbreak investigation.

Neuromyelitis optica-IgG in idiopathic inflammatory demyelinating disorders amongst Hong Kong Chinese.

BACKGROUND: Idiopathic inflammatory demyelinating disorders (IIDD) affect the central nervous system. In classical multiple sclerosis (CMS), brain, optic nerves [optic neuritis (ON)] and spinal cord [acute transverse myelitis (ATM)] are affected. In neuromyelitis optica (NMO), optic nerves and spinal cord are predominantly affected. NMO-IgG, an autoantibody targeting aquaporin-4, is a marker for NMO. We studied the frequency and clinical relevance of NMO-IgG seropositivity in IIDD patients. METHODS: Neuromyelitis optica-IgG was detected by indirect immunofluorescence using primate cerebellum. RESULTS: Neuromyelitis optica-IgG was detected in six of 10 NMO patients (60%), six of 10 idiopathic relapsing transverse myelitis (IRTM) patients (60%), two of nine idiopathic relapsing ON patients (22%), one of 11 patients (9%) having single ON attack, one of 30 CMS patients (3%), and none of patients having single ATM attack or controls. Comparing NMO-IgG seropositive (n = 12) with NMO-IgG seronegative (n = 8) patients having NMO or IRTM, NMO-IgG seropositivity was associated with a higher relapse rate in first 2 years, 1.5 and 0.6 attacks/year for seropositive and seronegative groups respectively (P = 0.006), and non-significant trend towards more severe ON and myelitis with poorer clinical outcome. CONCLUSION: Neuromyelitis optica -IgG facilitates diagnosis of NMO spectrum disorders. NMO-IgG seropositivity is associated with higher relapse rate in first 2 years.

Effects of plasticisers and related compounds on the expression of the soluble form of catechol-O-methyltransferase in MCF-7 cells.

Previously we have shown that E2 down regulates S-COMT expression. Here the effects of four phthalate esters and 4-(tert-octyl)phenol on the intra-cellular levels of S-COMT and COMT activity were studied in MCF-7 cells as a measure of estrogenic activity of these compounds. The four phthalate esters caused significant reductions in both S-COMT protein and COMT activity levels. These effects were inhibited by the ERalpha receptor antagonist ICI182780. 4-(tert-octyl)phenol also caused reductions in these parameters, but the effects were not abolished by ICI182780. Assay of S-COMT protein levels represents a simple and convenient method of assessing the estrogenic potential of a compound.

Estrogenic phenol and catechol metabolites of PCBs modulate catechol-O-methyltransferase expression via the estrogen receptor: potential contribution to cancer risk.

Commercial PCB mixtures have been shown to induce liver tumors in female rats and this effect has been attributed to the effects of PCBs on estrogen metabolism. Catechol metabolites of PCBs are potent inhibitors of COMT activity and are likely to contribute significantly to reduced clearance of genotoxic catechol metabolites of estrogen. The effect of PCB metabolites on COMT expression in cultured cells was investigated to explore potential mechanisms by which PCB exposure alters catechol estrogen clearance. We hypothesize that estrogenic PCB metabolites may contribute to reduction of COMT expression via interaction with the estrogen receptor. To test this hypothesis, human MCF-7 cells were exposed to PCB analogues and the expression of COMT determined. Western blot analysis demonstrated that COMT protein levels were statistically significantly reduced by both the phenolic and the catechol compounds, an effect which was abolished by the anti-estrogen, ICI182780. The above suggests that COMT levels may be reduced by estrogenic PCB metabolites, via interactions between PCB metabolites and the ER. It supports the hypothesis that both phenolic and catechol metabolites of PCBs may contribute to PCB-mediated carcinogenesis through reduction of COMT levels and activities and subsequent reduction in clearance of endogenous and xenobiotic catechols.

IGG: A tool to integrate GeneChips for genetic studies.

To facilitate genetic studies using high-throughput genotyping technologies, we have developed an open source tool to integrate genotype data across the Affymetrix and Illumina platforms. It can efficiently integrate a large amount of data from various GeneChips, add genotypes of the HapMap Project into a specific project, flexibly trim and export the integrated data with different formats of popular genetic analysis tools, and highly control the quality of genotype data. Furthermore, this tool has sufficiently simplified its usage through its user-friendly graphic interface and is independent of third-party databases. IGG has successfully been applied to a genome-wide linkage scan in a Charcot-Marie-Tooth disease pedigree by integrating three types of GeneChips and HapMap project genotypes.

Quantitative susceptibility mapping as an indicator of subcortical and limbic iron abnormality in Parkinson's disease with dementia.

Late stage Parkinson's disease (PD) patients were commonly observed with other non-motor comorbidities such as dementia and psychosis. While abnormal iron level in the substantia nigra was clinically accepted as a biomarker of PD, it was also suggested that the increased iron deposition could impair other brain regions and induce non-motor symptoms. A new Magnetic Resonance Imaging (MRI) called Quantitative Susceptibility Mapping (QSM) has been found to measure iron concentration in the grey matter reliably. In this study, we investigated iron level of different subcortical and limbic structures of Parkinson's disease (PD) patients with and without dementia by QSM. QSM and volumetric analysis by MRI were performed in 10 PD dementia (PDD) patients (73 ±â€¯6 years), 31 PD patients (63 ±â€¯8 years) and 27 healthy controls (62 ±â€¯7 years). No significant differences were observed in the L-Dopa equivalent dosage for the two PD groups (p = 0.125). Putative iron content was evaluated in different subcortical and limbic structures of the three groups, as well as its relationship with cognitive performance. One-way ANCOVA with FDR adjustment at level of 0.05, adjusted for age and gender, showed significant group differences for left and right hippocampus (p = 0.015 & 0.032, respectively, BH-corrected for multiple ROIs) and right thalamus (p = 0.032, BH-corrected). Post-hoc test with Bonferroni's correction suggested higher magnetic susceptibility in PDD patients than healthy controls in the left and right hippocampus (p = 0.001 & 0.047, respectively, Bonferroni's corrected), while PD patients had higher magnetic susceptibility than the healthy controls in right hippocampus and right thalamus (p = 0.006 & 0.005, respectively, Bonferroni's corrected). PDD patients also had higher susceptibility than the non-demented PD patients in left hippocampus (p = 0.046, Bonferroni's corrected). The magnetic susceptibilities of the left and right hippocampus were negatively correlated with the Mini-Mental State Examination score (r = -0.329 & -0.386, respectively; p < 0.05). This study provides support for iron accumulation in limbic structures of PDD and PD patients and its correlation with cognitive performance, however, its putative involvement in development of non-motor cognitive dysfunction in PD pathogenesis remains to be elucidated.

Nonthymoma early-onset- and late-onset-generalized myasthenia gravis--a retrospective hospital-based study.

OBJECTIVE: Acquired myasthenia gravis (MG) is predominantly due to nicotinic acetylcholine receptor (AChR) autoantibodies (Ab). Differences between nonthymoma early-onset and late-onset MG were reported. We studied the clinical and serological characteristics of nonthymoma AChR Ab-positive-generalized MG patients. PATIENTS AND METHODS: Chinese AChR Ab-positive-generalized MG patients who had generalized disease for 3 years or longer were studied. RESULTS: Among 41 such patients, 25 (61%) were female. The mean onset age was 43.5 years (range 9-78 years) and the mean follow-up duration was 7.8 years (range 3-20 years). Sixteen (39%) patients had late-onset disease (onset age >or=50 years). Compared to early-onset patients (onset age <50 years), late-onset patients were characterized by male predominance (p=0.002), absence of thymic lymphofollicular hyperplasia (p=0.036), and a higher striated muscle Ab seropositivity rate (94% versus 4%, p<0.001). Although there was no statistically significant difference in clinical severity and outcome or response to treatment between late-onset and early-onset patients, 50% and 75% of late-onset patients had moderate or severe disease at onset and worst status, respectively, compared to 28% and 52% for early-onset patients at onset and worst status, respectively. Also 63% of late-onset patients had disease progressed within first 3 years compared to only 40% of early-onset patients did. CONCLUSION: Nonthymoma late-onset-generalized MG patients were common among Hong Kong Chinese, with a statistically non-significant trend that it was clinically more severe than early-onset MG but with similar clinical outcome or response to treatment; >90% of these patients were seropositive for striated muscle Ab.

Mah-jong-induced seizures: case reports and review of twenty-three patients.

'Mah-jong epilepsy' is a rare reflex epilepsy syndrome, manifesting as recurrent epileptic seizures triggered by either playing or just watching mah-jong. We present three patients with this condition and review all the reported cases. Mah-jong-induced seizures can be considered a subtype of cognition-induced epilepsy. Nonetheless, these patients have distinctive clinical and electrophysiological features: late age of onset, different seizure patterns, single seizure-trigger, lack of spontaneous seizures, and electroencephalographic findings not supportive of idiopathic generalised epilepsy. The pathophysiological mechanism underlying mah-jong-induced seizures may be different from the other cognition-associated reflex epileptic phenomena.

Idiopathic inflammatory demyelinating disorders after acute transverse myelitis.

Acute transverse myelitis (ATM) is commonly para-infectious. Recurrent ATM occurs in connective tissue diseases (CTD), infective myelitis and idiopathic inflammatory demyelinating disorders (IIDD) including multiple sclerosis (MS) and neuromyelitis optica (NMO). Previous studies might include NMO and idiopathic recurrent transverse myelitis (IRTM) as MS. The aim was to study the outcome of patients after a first attack of idiopathic ATM. Idiopathic ATM patients over a 6-year period were retrospectively studied. Known causes of myelopathy were excluded. Among 32 patients studied, 20 (63%) had single ATM attack upon follow up for 39-93 months, three developed recurrent ATM related to CTD (two systemic lupus erythematosus and one anti-Ro antibody positive) and nine (28.1%) developed recurrent neuroinflammation compatible with IIDD. Among IIDD patients, three had NMO, two restricted variant of NMO, three IRTM and one classical MS. NMO, its variant and IRTM had mean spinal MRI abnormality of 3.7, 2.1 and 3.9 vertebral segments respectively while non-recurrent ATM had 1.6 vertebral segments. Four (80%) of the five patients with NMO or its variant had poor neurological prognosis versus only one (5%) of non-recurrent ATM patients. IRTM patients had advanced mean onset age, 62 years vs. 43 years for non-recurrent ATM patients. In IIDD patients presenting with ATM as first attack of neuroinflammation, NMO and its variant (56%) were most frequent, then IRTM (33%), with classical MS (11%) the rarest. As long-term treatments for NMO are different from MS, early recognition of NMO and its variant is important for prevention of serious neurological deficits.

Myopia as a latent phenotype of a pleiotropic gene positively selected for facilitating neurocognitive development, and the effects of environmental factors in its expression.

Myopia has become an almost pandemic problem in many populations. There are compelling evidence to suggest that myopia is a hereditary condition. However, myopia would constitute a definite selection disadvantage during most stages of human evolution, which is incompatible with its moderate to high prevalence in most modern populations. The rapid upsurge of myopia over just a few decades also implies that its inheritance does not follow any of the usual patterns, and environmental factors may have an important role in precipitating its occurrence in those who are genetically predisposed. Previous studies showed that myopes were, on average, more intelligent than non-myopes, and this association had been attributed to a biological link between eye growth and brain development. We propose a pleiotropic genetic model to explain the atypical epidemiologic and inheritance pattern of myopia and its relationship with neurocognitive development. This pleiotropic gene was positively selected for its facilitation of human intelligence. The myopic component is a latent phenotype; myopia will not be expressed unless some novel external factors are encountered (i.e. a "quirk" phenomenon). Therefore, the myopic component was selectively neutral in our ancestral environment. The net gain in Darwinian fitness enables the pleiotropic gene to attain a high frequency in the human population, as reflected by our current prevalence of myopia.

Uncoupling proteins: targets of endocrine disruptors?

The roles of uncoupling proteins (UCPs) are discussed. Particular attention has been paid to the roles of UCP2 to UCP5 as agents mediating thermogenesis, and to the concept of limited or "mild" uncoupling as a means of reducing oxidative stress. The role of the endocrine system, thyroid hormones and catecholamines, in regulating expression of UCPs is also discussed.

Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.

BACKGROUND/AIMS: Pseudoexfoliation syndrome (PXF) was recently found to be associated with increased expression of transforming growth factor beta(1) (TGFbeta(1)) in the aqueous humour. As concern has been raised regarding anti-TGFbeta therapy, which can potentially disrupt the maintenance of anterior chamber associated immune deviation, the authors explored the levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF) in aqueous humour to determine if these may represent alternative therapeutic targets. METHODS: Aqueous humour samples were collected from patients who underwent routine cataract surgery. All patients were categorised into three main groups-PXF, uveitis, and control. The PXF group was further subcategorised into three grades based on the density of the exfoliative material observed on biomicroscopy, as well as the presence or absence of glaucoma. TIMP-1, MMP-9, and CTGF levels were measured using specific enzyme immunoassays (ELISA). RESULTS: Eyes with PXF had significantly higher aqueous humour TIMP-1 concentration (n = 56, mean (SE), 9.76 (1.10) ng/ml) compared with controls (n = 112, 5.73 (0.43) ng/ml, p<0.01). Similarly, the CTGF level in PXF eyes (n = 36, 4.38 (0.65) ng/ml) was higher than controls (n = 29, 2.35 (0.46) ng/ml, p<0.05). Further, the CTGF concentration in the PXF glaucoma group is significantly higher compared with PXF eyes without glaucoma (6.03 (1.09) ng/ml v 2.73 (0.45) ng/ml, p<0.01). The MMP-9 levels were low and below detection limit in all PXF and control samples with no statistical difference between groups. CONCLUSION: A raised TIMP-1 level and a low MMP-9 level in aqueous humour of PXF eyes may imply a downregulation in proteolytic activity. The increased CTGF concentration supports the proposed fibrotic pathology of PXF. Regulation of MMP/TIMP expression and anti-CTGF therapy may offer potential therapeutic avenues for controlling PXF associated ocular morbidity.

Prose memory in patients with idiopathic Parkinson's disease.

BACKGROUND: The findings of previous studies have suggested that verbal memory impairments were observed in people suffering from Parkinson's disease (PD). Very few studies have examined the comprehensive profile of prose memory deficits that challenges people with PD. METHODS: Prose memory of 19 patients with PD was examined. Their performance in three constructs, namely recall accuracy, temporal sequence, and distortions, during immediate, delayed and recognition trials was studied. RESULTS: The patients with PD performed significantly worse in recall accuracy and temporal sequencing of information in the immediate recall trial. During the recognition trial, they made more false alarms than their healthy counterparts. CONCLUSIONS: Our findings confirm that the performance of people with PD in immediate recall of a prose was impaired. However, the level of performance in subsequent learning and delayed recall trials became comparable to that of the normal controls. The deficit remaining after multiple learning trials was the significantly high false alarms committed in the recognition trial. Our findings highlight the importance of qualitative analysis, in addition to quantitative evaluation, of prose memory in PD.