Language, speech, and oromotor function in children with Pompe disease.

Advances in the treatment of Pompe disease have improved life expectancy and quality of life, but speech and oromotor function remain significantly affected. The purpose of this study was to expand on existing data and present new findings of speech acoustic and physiologic outcomes in Pompe disease. A retrospective analysis was carried out on results of speech, language and oromotor tests carried out in 14 children diagnosed with Pompe disease. The assessment battery included standardized tests of language, picture naming, maximum performance tests, and oromotor resistance tasks. Speech production was scored with respect to intelligibility, hypernasality, and articulatory accuracy. Language delays ranged from mild to severe in 1/3 of the children. Reduced speech intelligibility, disordered articulation, and hypernasality were present in at least 2/3 of the children. Maximum performance tests all fell at least 1 SD below normative means. Significant correlations were identified between maximum phonation time and articulation and between the S/Z ratio and intelligibility. Positive correlations were also found between tongue strength and articulation. Results confirm previous reports of speech and language function in Pompe disease. Clinical acoustic measures provide important insights into the speech deficits in this group of children and suggest possible treatment strategies.

Airway abnormalities in very early treated infantile-onset Pompe disease: A large-scale survey by flexible bronchoscopy.

Early enzyme replacement therapy (ERT) improve long-term outcomes in patients with infantile-onset Pompe disease (IOPD). Our cohort of patients with IOPD at Taipei Veterans General Hospital (TVGH) joined Taiwan Pompe newborn screening program from 2008, testing more than one million newborns until 2018. By 2010, we had established rapid diagnostic strategies. Now, the average age of ERT initiation starts at an average age of <10 days-old, the earliest group in the world. However, they still presented some airway problems. We present a retrospective study focused on airway abnormalities in these patients along 8 years of observation. Fifteen patients with IOPD, who received very early treatment at a mean age of 8.94 ± 3.75 days, underwent flexible bronchoscopy (FB) for dynamic assessment of the whole airway. Long-term clinical outcomes and relevant symptoms of the upper airway were assessed. All patients in the study had varying degrees of severity of upper airway abnormalities and speech disorders. The three oldest children (Age 94, 93, and 88 months, respectively) had poor movement of the vocal cords with reduced abduction and adduction and had silent aspiration of saliva through the glottis during respiration. This is the largest cohort study presented to date about airway abnormalities in very early treated patients with IOPD patients by FB. Despite very early treatment, we observed upper airway abnormalities in these IOPD patients. In IOPD, upper airway abnormalities seem inevitable over time. We suggest early and continuous monitoring for all IOPD patients, even with early and regular treatment.

The Evaluation of Physical Stillness with Wearable Chest and Arm Accelerometer during Chan Ding Practice.

Chan Ding training is beneficial to health and emotional wellbeing. More and more people have taken up this practice over the past few years. A major training method of Chan Ding is to focus on the ten Mailuns, i.e., energy points, and to maintain physical stillness. In this article, wireless wearable accelerometers were used to detect physical stillness, and the created physical stillness index (PSI) was also shown. Ninety college students participated in this study. Primarily, accelerometers used on the arms and chest were examined. The results showed that the PSI values on the arms were higher than that of the chest, when participants moved their bodies in three different ways, left-right, anterior-posterior, and hand, movements with natural breathing. Then, they were divided into three groups to practice Chan Ding for approximately thirty minutes. Participants without any Chan Ding experience were in Group I. Participants with one year of Chan Ding experience were in Group II, and participants with over three year of experience were in Group III. The Chinese Happiness Inventory (CHI) was also conducted. Results showed that the PSI of the three groups measured during 20-30 min were 0.123 ± 0.155, 0.012 ± 0.013, and 0.001 ± 0.0003, respectively (p < 0.001 ***). The averaged CHI scores of the three groups were 10.13, 17.17, and 25.53, respectively (p < 0.001 ***). Correlation coefficients between PSI and CHI of the three groups were -0.440, -0.369, and -0.537, respectively (p < 0.01 **). PSI value and the wearable accelerometer that are presently available on the market could be used to evaluate the quality of the physical stillness of the participants during Chan Ding practice.

Photoelectro-Fenton mineralization of phenol through optimization of ferrous regeneration.

The degradation of phenol in acidic solution at pH 3 has been investigated under various photo- and electrochemical conditions. A laboratory-scale reactor on which were mounted net electrodes (RuO2/IrO2-coated Ti anodes (DSA) and stainless steel cathodes) and 254 nm UV lamps was established to effectively reduce ferric reagents. The experimental results of the photoelectron-chemical reaction suggested that the current efficiency of reducing ferric ion was improved by increasing the number of electrodes used, and the UV lamps were important to inducing the reduction of ferric carboxylates, which were the major intermediates that were formed upon a particular degree of phenol oxidation. Accordingly, the addition of an initial concentration of 400 ppm ferrous salt and 10,200 ppm hydrogen peroxide (in a continuous mode) resulted in the removal of over 92 % of TOC (initial phenol = 2,000 ppm, TOC = 1,532 ppm) by 4 h of the photoelectro-Fenton and the sequential 2 h of the photo-Fenton processes. HPLC was utilized to monitor the formation of aromatic and carboxylate byproducts, and revealed that the aid of photo irradiation eliminated most of the oxalate residue from the final solution, which would have contributed to the 25 % of the TOC that was inactive in the electrolytic system.

Regulation of zebrafish CYP3A65 transcription by AHR2.

CYP3A proteins are the most abundant CYPs in the liver and intestines, and they play a pivotal role in drug metabolism. In mammals, CYP3A genes are induced by various xenobiotics through processes mediated by PXR. We previously identified zebrafish CYP3A65 as a CYP3A ortholog that is constitutively expressed in gastrointestinal tissues, and is upregulated by treatment with dexamethasone, rifampicin or tetrachlorodibenzo-p-dioxin (TCDD). However, the underlying mechanism of TCDD-mediated CYP3A65 transcription is unclear. Here we generated two transgenic zebrafish, Tg(CYP3A65S:EGFP) and Tg(CYP3A65L:EGFP), which contain 2.1 and 5.4 kb 5' flanking sequences, respectively, of the CYP3A65 gene upstream of EGFP. Both transgenic lines express EGFP in larval gastrointestinal tissues in a pattern similar to that of the endogenous CYP3A65 gene. Moreover, EGFP expression can be significantly induced by TCDD exposure during the larval stage. In addition, EGFP expression can be stimulated by kynurenine, a putative AHR ligand produced during tryptophan metabolism. AHRE elements in the upstream regulatory region of the CYP3A65 gene are indispensible for basal and TCDD-induced transcription. Furthermore, the AHR2 DNA and ligand-binding domains are required to mediate effective CYP3A65 transcription. AHRE sequences are present in the promoters of many teleost CYP3 genes, but not of mammalian CYP3 genes, suggesting that AHR/AHR2-mediated transcription is likely a common regulatory mechanism for teleost CYP3 genes. It may also reflect the different environments that terrestrial and aquatic organisms encounter.

Removal of citrate and hypophosphite binary components using Fenton, photo-Fenton and electro-Fenton processes.

Both citrate and hypophosphite in aqueous solution were degraded by advanced oxidation processes (Fe2+/H2O2, UV/Fe2+/H2O2, and electrolysis/ Fe2+/H2O2) in this study. Comparison of these techniques in oxidation efficiency was undertaken. It was found that Fenton process could not completely degrade citrate in the presence of hypophosphite since it caused a series inhibition. Therefore, UV light (photo-Fenton) or electron current (electro-Fenton) was applied to improve the degradation efficiency of the Fenton process. Results showed that both photo-Fenton and electro-Fenton processes could overcome the inhibition of hypophosphite, especially the electro-Fenton.

CYP3C1, the first member of a new cytochrome P450 subfamily found in zebrafish (Danio rerio).

We report a new cytochrome P450 (CYP) subfamily CYP3C and the cloning through PCR from zebrafish (Danio rerio) of the first member, CYP3C1. The CYP3C1 gene is on Chromosome 3 with 13 ORF exons encoding a 505 amino acid protein which has 44-54% identities with mammalian and teleost CYP3A and CYP3B forms. As evidenced by spectral analysis, the CYP3C1 protein heterologously expressed in yeast is functional. In silico analysis identified, on the same region of the chromosome, three more genes encoding CYP3C1-like proteins that formed a clade with CYP3C1 in a phylogenetic tree. Using RT-PCR, the CYP3C1 mRNA was detected in 1-6dpf embryo/larvae and in adult fish liver and seven extrahepatic tissues. Whole-mount in situ hybridization using a riboprobe demonstrated expression in the brain during 12-120 hpf. At the 120 hpf larval stage, CYP3C1 mRNA was also detected in the pharynx and gastrointestinal tract. TCDD, dexamethasone, and rifampicin, which up-regulated CYP3A65 mRNA in zebrafish larvae, did not alter the CYP3C1 transcript levels suggesting regulatory differences between CYP3A and CYP3C enzymes in this species.