The effect of anticonvulsant use on bone mineral density in non-ambulatory children with cerebral palsy.

INTRODUCTION: Studies showed that use of anticonvulsants (antiepileptic drugs) might be associated with reduced bone mineral density. The primary objective of this study was to evaluate the effect of anticonvulsants on bone mineral density in non-ambulatory children with cerebral palsy. The secondary objective was to identify their risk factors for low bone mineral density. METHODS: This case series with internal comparisons was conducted in a paediatric residential rehabilitation centre in Hong Kong. Overall, 32 patients were enrolled. The study group comprised 18 patients (6 males, 12 females) aged 5.0 to 19.5 years (mean ± standard deviation, 13.8 ± 4.7 years); all were prescribed anticonvulsant therapy for more than 2 years. The comparison group comprised 14 patients (6 males, 8 females) aged 7.0 to 19.1 years (mean, 16.4 ± 3.0 years) who were concomitant non-ambulatory residents with cerebral palsy and were not prescribed any anticonvulsant therapy prior to study recruitment. Patients underwent a physical examination, blood tests, nutritional assessment, and dual-energy X-ray absorptiometry scan of the total body less head. Z-scores were calculated. RESULTS: There was no significant difference in Z-scores of total body less head between groups. Among children with low bone mineral density (Z-scores ≤-2.0) and normal bone mineral density, multivariate analysis revealed that higher weight-for-age Z-score (adjusted odds ratio=0.015) and presence of puberty (adjusted odds ratio=0.027) were independent factors for bone mineral density improvement. Hosmer-Lemeshow goodness of fit test (P=0.315) was not significant. Nagelkerke R(2) was 0.677, signifying a relatively well-fitting model. CONCLUSION: There was no evidence that anticonvulsant therapy has any detrimental effect on bone mineral density in non-ambulatory children with cerebral palsy. A low weight-for-age Z-score was associated with low bone mineral density. Early nutritional intervention to optimise body weight may help to increase bone mineral density.

Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.

BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.

Novel use of idebenone in Leber's hereditary optic neuropathy in Hong Kong.

We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed.

A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency.

A 15-year-old Chinese male with infantile-onset hypotonia, developmental delay, ptosis, and oculogyric episodes presented with a history of chronic diarrhoea since the age of 5 years. At presentation, he had an exacerbation of diarrhoeal symptoms resulting in dehydration and malnutrition with a concurrent severe chest infection. In view of his infantile-onset hypotonia, oculogyric crises, and protracted diarrhoea, an autonomic disturbance related to neurotransmitters was suspected. Urine organic acid profiling was compatible with aromatic L-amino acid decarboxylase deficiency. The diagnosis was confirmed based on cerebrospinal fluid analysis and genetic mutation analysis. The patient was treated with a combination of bromocriptine, selegiline, and pyridoxine; a satisfactory reduction in diarrhoea ensued. Our report highlights the importance of urine organic acid screening in infantile-onset hypotonia, especially when accompanied by oculogyric crises, and severe diarrhoea which could manifest as a result of autonomic disturbance.

Successful use of extracorporeal membrane oxygenation in a patient with combined pulmonary and systemic embolisation.

We present a highly unusual case of massive pulmonary embolism with secondary paradoxical systemic embolisation that was successfully resuscitated with veno-arterial extracorporeal membrane oxygenation (ECMO). This enabled subsequent successful bridging to pulmonary embolectomy.

GaN epitaxial layers prepared on nano-patterned Si(001) substrate.

We report the growth of GaN epitaxial layer on Si(001) substrate with nano-patterns prepared by dry etching facility used in integrated circuit (IC) industry. It was found that the GaN epitaxial layer prepared on nano-patterned Si(001) substrate exhibits both cubic and hexagonal phases. It was also found that threading dislocation observed from GaN prepared on nano-patterned Si(001) substrate was significantly smaller than that prepared on conventional unpatterned Si(111) substrate. Furthermore, it was found that we can reduce the tensile stress in GaN epitaxial layer by about 78% using the nano-patterned Si(001) substrate.

Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese.

Tyrosine hydroxylase deficiency is a rare neurotransmitter disorder affecting the rate-limiting step in catecholamine biosynthesis. There are about 40 cases reported worldwide. Here, we report the biochemical and molecular findings of eight unrelated Chinese patients with tyrosine hydroxylase deficiency. We have identified eight novel mutations with 5 missense, 2 nonsense and 1 splicing mutations in the TH gene, namely p.R153X, p.R169X, p.G294R, p.G315S, p.A385V, p.I394T, p.G408R, and c.1163+5G>C. The mutations of the TH gene in Chinese are heterogeneous.

Psychiatric comorbidity of internet addiction in college students: an interview study.

OBJECTIVE: This study was aimed to evaluate the association between Internet addiction and depressive disorder, social phobia and adult attention-deficit/hyperactivity disorder (ADHD) in a sample of Taiwanese college students; and examine gender differences in the psychiatric comorbidity of Internet addiction in this student population. METHODS: Two hundred sixteen college students (132 males, 84 females) were recruited. Internet addiction, major depressive disorder, dysthymic disorder, social phobia, and adult ADHD of all participants were diagnosed based on psychiatric diagnostic interview. RESULTS: This study revealed that adult ADHD and depressive disorders were associated with Internet addiction among college students. However, depressive disorders were associated with Internet addiction in the males but not the females. CONCLUSION: With these results, it seems reasonable to suggest that effective evaluation of, and treatment for, adult ADHD and depressive disorders is required for college students with Internet addiction.

Comparison of oesophagogastroduodenoscopy findings and diagnostic value in neurologically impaired children and 'normal' children.

OBJECTIVES: To review the oesophagogastroduodenoscopy findings in children with severe neurological impairment and 'normal' children, over a 7-year period from 2000 to 2007. DESIGN: Retrospective study. SETTING: Paediatric Unit of Caritas Medical Centre, Hong Kong. MAIN OUTCOME MEASURES: The frequencies of Helicobacter pylori status, peptic ulceration, and oesophagitis were compared. The diagnostic value of oesophagogastroduodenoscopy in these two groups of children was also examined. PATIENTS: Patient data were retrieved from the Hospital Authority Clinical Management system, excluding those under surgical care. The children were divided into two groups: 'normal' and neurologically impaired. Their demographic data, indications for oesophagogastroduodenoscopy, endoscopy diagnoses, and Helicobacter pylori status were compared, as was the diagnostic value of oesophagogastroduodenoscopy. RESULTS: From 2000 to 2007, 223 oesophagogastroduodenoscopies were performed in 176 patients aged 3 to 22 years; 134 were performed in 'normal' children (median age, 14; range, 3-22 years) and 89 in neurologically impaired children (median age, 12; range, 3-20 years). The three most common indications in 'normal' children were: epigastric pain (60%), gastro-intestinal bleeding (13%), and vomiting (7%). In neurologically impaired children, they were gastro-intestinal bleeding (51%), assessment for percutaneous endoscopic gastrostomy (27%), and follow-up for previous lesions (9%). Among 'normal' children, 14 had duodenal ulcers (associated with Helicobacter pylori in 13), but no patients had gastric ulcers or oesophagitis. Among neurologically impaired children, one had a Helicobacter pylori-negative duodenal ulcer, and four had gastric ulcers (three were Helicobacter pylori-positive). Twenty-four neurologically impaired children had oesophagitis. Neurologically impaired children had significantly more oesophagitis and gastric ulcers (P<0.001 and P=0.004, respectively) but less duodenal ulcers (P=0.024). In 111 children who had gastric biopsies, the Helicobacter pylori infection rate was 35% (31% in 'normal' children and 43% in the neurologically impaired). The diagnostic value was 37% in 'normal' children and 81% in the neurologically impaired (P<0.001). The overall diagnostic value of oesophagogastroduodenoscopy was 50%. CONCLUSION: The clinical presentation and endoscopic findings in 'normal' and neurologically impaired children were discrepant. Oesophagogastroduodenoscopy appeared to confer greater diagnostic value in neurologically impaired than 'normal' children. Diagnostic values in our unit were comparable to reports from western studies.

Tunable S-band erbium-doped triple-ring laser with single-longitudinal-mode operation.

We propose and demonstrate a tunable and stable single-longitudinal-mode (SLM) erbium fiber laser with a passive triple-ring cavity structure in S-band operation. The proposed laser is fundamentally structured by using three different lengths of ring cavities, which serve as the mode filters. When a mode-restricting intracavity fiber Fabry-Perot tunable filter (FFP-TF) is combined, the proposed resonator can guarantee a tunable and stable SLM laser oscillation. Moreover, the performances of the output power, wavelength stability, tuning range, and side-mode suppression ratio (SMSR) are studied.

TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae.

We describe the cloning and molecular analysis of TRK2, the gene likely to encode the low-affinity K+ transporter in Saccharomyces cerevisiae. TRK2 encodes a protein of 889 amino acids containing 12 putative membrane-spanning domains (M1 through M12), with a large hydrophilic region between M3 and M4. These structural features closely resemble those contained in TRK1, the high-affinity K+ transporter. TRK2 shares 55% amino acid sequence identity with TRK1. The putative membrane-spanning domains of TRK1 and TRK2 share the highest sequence conservation, while the large hydrophilic regions between M3 and M4 exhibit the greatest divergence. The different affinities of TRK1 trk2 delta cells and trk1 delta TRK2 cells for K+ underscore the functional independence of the high- and low-affinity transporters. TRK2 is nonessential in TRK1 or trk1 delta haploid cells. The viability of cells containing null mutations in both TRK1 and TRK2 reveals the existence of an additional, functionally independent potassium transporter(s). Cells deleted for both TRK1 and TRK2 are hypersensitive to low pH; they are severely limited in their ability to take up K+, particularly when faced with a large inward-facing H+ gradient, indicating that the K+ transporter(s) that remains in trk1 delta trk2 delta cells functions differently than those of the TRK class.

Roles of multiple glucose transporters in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, TRK1 and TRK2 are required for high- and low-affinity K+ transport. Among suppressors of the K+ transport defect in trk1 delta trk2 delta cells, we have identified members of the sugar transporter gene superfamily. One suppressor encodes the previously identified glucose transporter HXT1, and another encodes a new member of this family, HXT3. The inferred amino acid sequence of HXT3 is 87% identical to that of HXT1, 64% identical to that of HXT2, and 32% identical to that of SNF3. Like HXT1 and HXT2, overexpression of HXT3 in snf3 delta cells confers growth on low-glucose or raffinose media. The function of another new member of the HXT superfamily, HXT4 (previously identified by its ability to suppress the snf3 delta phenotype; L. Bisson, personal communication), was revealed in experiments that deleted all possible combinations of the five members of the glucose transporter gene family. Neither SNF3, HXT1, HXT2, HXT3, nor HXT4 is essential for viability. snf3 delta hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells are unable to grow on media containing high concentrations of glucose (5%) but can grow on low-glucose (0.5%) media, revealing the presence of a sixth transporter that is itself glucose repressible. This transporter may be negatively regulated by SNF3 since expression of SNF3 abolishes growth of hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells on low-glucose medium. HXT1, HXT2, HXT3, and HXT4 can function independently: expression of any one of these genes is sufficient to confer growth on medium containing at least 1% glucose. A synergistic relationship between SNF3 and each of the HXT genes is suggested by the observation that SNF2 hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells and snf3 delta HXT1 HXT2 HXT3 HXT4 cells are unable to grow on raffinose (low fructose) yet SNF3 in combination with any single HXT gene is sufficient for growth on raffinose. HXT1 and HXT3 are differentially regulated. HXT1::lacZ is maximally expressed during exponential growth whereas HXT3::lacZ is maximally expressed after entry into stationary phase.

Trinucleotide insertions, deletions, and point mutations in glucose transporters confer K+ uptake in Saccharomyces cerevisiae.

Deletion of TRK1 and TRK2 abolishes high-affinity K+ uptake in Saccharomyces cerevisiae, resulting in the inability to grow on typical synthetic growth medium unless it is supplemented with very high concentrations of potassium. Selection for spontaneous suppressors that restored growth of trk1delta trk2delta cells on K+-limiting medium led to the isolation of cells with unusual gain-of-function mutations in the glucose transporter genes HXT1 and HXT3 and the glucose/galactose transporter gene GAL2. 86Rb uptake assays demonstrated that the suppressor mutations conferred increased uptake of the ion. In addition to K+, the mutant hexose transporters also conferred permeation of other cations, including Na+. Because the selection strategy required such gain of function, mutations that disrupted transporter maturation or localization to the plasma membrane were avoided. Thus, the importance of specific sites in glucose transport could be independently assessed by testing for the ability of the mutant transporter to restore glucose-dependent growth to cells containing null alleles of all of the known functional glucose transporter genes. Twelve sites, most of which are conserved among eukaryotic hexose transporters, were revealed to be essential for glucose transport. Four of these have previously been shown to be essential for glucose transport by animal or plant transporters. Eight represented sites not previously known to be crucial for glucose uptake. Each suppressor mutant harbored a single mutation that altered an amino acid(s) within or immediately adjacent to a putative transmembrane domain of the transporter. Seven of 38 independent suppressor mutations consisted of in-frame insertions or deletions. The nature of the insertions and deletions revealed a striking DNA template dependency: each insertion generated a trinucleotide repeat, and each deletion involved the removal of a repeated nucleotide sequence.

The adaptive decision-making, risky decision, and decision-making style of Internet gaming disorder.

BACKGROUND: Persistent gaming, despite acknowledgment of its negative consequences, is a major criterion for individuals with Internet gaming disorder (IGD). This study evaluated the adaptive decision-making, risky decision, and decision-making style of individuals with IGD. METHODS: We recruited 87 individuals with IGD and 87 without IGD (matched controls). All participants underwent an interview based on the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) diagnostic criteria for IGD and completed an adaptive decision-making task; the Preference for Intuition and Deliberation Scale, Chen Internet Addiction Scale, and Barratt Impulsivity Scale were also assessed on the basis of the information from the diagnostic interviews. RESULTS: The results demonstrated that the participants in both groups tend to make more risky choices in advantage trials where their expected value (EV) was more favorable than those of the riskless choice. The tendency to make a risky choice in advantage trials was stronger among IGD group than that among controls. Participants of both groups made more risky choices in the loss domain, a risky option to loss more versus sure loss option, than they did in the gain domain, a risky option to gain more versus sure gain. Furthermore, the participants with IGD made more risky choices in the gain domain than did the controls. Participants with IGD showed higher and lower preferences for intuitive and deliberative decision-making styles, respectively, than controls and their preferences for intuition and deliberation were positively and negatively associated with IGD severity, respectively. CONCLUSIONS: These results suggested that individuals with IGD have elevated EV sensitivity for decision-making. However, they demonstrated risky preferences in the gain domain and preferred an intuitive rather than deliberative decision-making style. This might explain why they continue Internet gaming despite negative consequences. Thus, therapists should focus more on decision-making styles and promote deliberative thinking processes to mitigate the long-term negative consequences of IGD.

Risk factors of long bone fracture in non-ambulatory cerebral palsy children.

OBJECTIVES: To identify the risk factors for long bone fractures in non-ambulatory cerebral palsy children. DESIGN. Case-control study. SETTING: A residential rehabilitation centre in Hong Kong. PATIENTS: The fracture group comprised 19 (13 male, 6 female) cerebral palsy children aged 4 years 5 months to 18 years 11 months (mean, 10 years; standard deviation, 3 years 9 months), who had their first long bone fracture during the period June 1992 to May 2001 inclusive. The control group was composed of 90 (46 male, 44 female) concomitant cerebral palsy residents aged 6 years 1 month to 16 years 11 months (mean, 9 years 11 months; standard deviation, 2 years 4 months) with no history of long bone fracture. MAIN OUTCOME MEASURES: Presence of features considered relevant to the risk of fracture, namely: anthropometry, feeding practice, orthopaedic surgery and duration of postoperative immobilisation, extremity contracture, anti-epileptic medications, and general health status in the 12 months prior to the fracture. RESULTS: Of the 19 fracture episodes, 18 occurred in the femur and one in the tibia/fibula. Multivariate analysis revealed that weight for age Z scores (adjusted odds ratio=0.41, 95% confidence interval, 0.19-0.86) and recent postoperative immobilisation (weeks) [adjusted odds ratio=1.35, 95% confidence interval, 0.97-1.89] were independent predictors for fracture occurrence. CONCLUSION: Early intervention targeting these risk factors may reduce the fracture risk in non-ambulatory cerebral palsy children.

TRK2 is required for low affinity K+ transport in Saccharomyces cerevisiae.

TRK1, the gene encoding the high affinity K+ transporter in Saccharomyces cerevisiae, is nonessential due to the existence of a functionally independent low affinity transporter. To identify the gene(s) encoding the low affinity K+ transporter, we screened trk1 delta cells for mutants (Kla-) that require higher concentrations of K+ in the medium to support growth. trk1 delta trk2 mutants require up to tenfold higher concentrations of K+ to exhibit normal growth compared to trk1 delta TRK2 cells. K+ and 86Rb+ transport assays demonstrate that the mutant phenotype is due to defective K+ transport (uptake). Each of 38 independent mutants contains a mutation in the same gene, TRK2. Cells deficient for both high and low affinity K+ transport (trk1 delta trk2) exhibit hypersensitivity to low extracellular pH that can be suppressed by high concentrations of K+ but not Na+. TRK1 completely suppresses both the K+ transport defect and low pH hypersensitivity of trk2 cells, suggesting that TRK1 and TRK2 are functionally independent.

Atypical presentation of dopa-responsive dystonia: generalized hypotonia and proximal weakness.

Dopa-responsive dystonia (DRD) is an autosomal dominant disorder typically presenting as dystonia with diurnal variability. Described is an 8-year-old boy who had had waddling gait, generalized hypotonia, and proximal weakness since early childhood. He responded well to low-dose L-dopa. He had a point mutation of the GTP cyclohydrolase I gene. The patient's father and sister had the same mutation but did not have proximal weakness. GTP cyclohydrolase I deficiency can present with hypotonia and weakness.

Circadian rhythms, aging and memory.

In human beings and animal models, cognitive performance is often impaired in natural and experimental situations where circadian rhythms are disrupted. This includes a general decline in cognitive ability and fragmentation of behavioural rhythms in the aging population of numerous species. There is some evidence that rhythm disruption may lead directly to cognitive impairment; however, this causal link has not been made for effects due to aging. We have tested this link by examining rhythms and performance on contextual conditioning with the conditioned place preference task, in elderly, age-matched hamsters. Young healthy hamsters developed a preference for a context that is paired with the opportunity to engage in wheel-running (experiment 1). Aged animals with consolidated locomotor rhythms developed similar degrees of preference, whereas the age-matched hamsters with fragmented rhythms did not (experiment 2). The degree of preference was also correlated with activity amplitude. These results support the notion that age-related rhythm fragmentation contributes to the age-related memory decline.