rad21 Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration

Previously, we identified RAD21(R450C) from a peripheral sclerocornea pedigree. Injection of this rad21 variant mRNA into Xenopus laevis embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous rad21 variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in X. laevis embryos. In X. laevis embryos injected with rad21 mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21(R450C) variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development

The photometric observation of the quasi-simultaneous mutual eclipse and occultation between Europa and Ganymede on 22 August 2021

Mutual events (MEs) are eclipses and occultations among planetary natural satellites. Most of the time, eclipses and occultations occur separately. However, the same satellite pair will exhibit an eclipse and an occultation quasi-simultaneously under particular orbital configurations. This kind of rare event is termed as a quasi-simultaneous mutual event (QSME). During the 2021 campaign of mutual events of jovian satellites, we observed a QSME between Europa and Ganymede. The present study aims to describe and study the event in detail. We observed the QSME with a CCD camera attached to a 300-mm telescope at the Hong Kong Space Museum Sai Kung iObservatory. We obtained the combined flux of Europa and Ganymede from aperture photometry. A geometric model was developed to explain the light curve observed. Our results are compared with theoretical predictions (O-C). We found that our simple geometric model can explain the QSME fairly accurately, and the QSME light curve is a superposition of the light curves of an eclipse and an occultation. Notably, the observed flux drops are within 2.6% of the theoretical predictions. The size of the event central time O-Cs ranges from -14.4 to 43.2 s. Both O-Cs of flux drop and timing are comparable to other studies adopting more complicated models. Given the event rarity, model simplicity and accuracy, we encourage more observations and analysis on QSMEs to improve Solar System ephemerides.Comment: 23 pages, 5 appendixes, 16 figures, 7 table

Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: Consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

More than 360 million persons worldwide (6% of the world population) are chronically infected by the hepatitis B Virus (HBV). Although the incidence of HBV infection has dramatically declined since the implementation of universal immunization programs in several countries and blood-donor screening, a significant number of children are still infected each year, often developing chronic infection and requiring appropriate followup [1]. Despite a rather benign course of chronic hepatitis B (CHB) during childhood and adolescence, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma (HCC), respectively, before adulthood [2,3]. Such a risk for HCC rises to 9-24% when considering the whole lifetime, with an incidence of cirrhosis of 2-3% per year [4,5]. Worldwide universal vaccination remains the goal for eliminating HBV infection and its complications. Treatment of CHB in childhood has been hampered by the chronic delay in licensing new drugs for pediatric use. Safe and effective antiviral therapies are available in adults, but few are labeled for the use in children, and an accurate selection of whom to treat and the identification of the right timing for treatment are needed to optimize response and reduce the risk of antiviral resistance. Although several guidelines on the management of adult patients with CHB have been published by major international societies, the clinical approach to infected children is still evolving, and is mostly based on consensus of expert opinion [6-9]

Lutte antivectorielle contre les tiques en médecine humaine

STRASBOURG ILLKIRCH-Pharmacie (672182101) / SudocSudocFranceF

The prevalence of cognitive impairment and dementia among hypertensiveelderly as a whole and among different classes of anti-hypertensivedrug users in a regional geriatric clinic in Hong Kong

published_or_final_versionMedical SciencesMasterMaster of Medical Science

Driving experience and the risk of traffic accident among motorcyclists

In a case-control study on the risk of traffic accidents among motorcyclists in Singapore, we demonstrated an inverse monotonic relationship between accident risk and driving experience. As compared to drivers with less that 1 yr of driving experience, the odds ratios (adjusted for race, age and frequency of riding) for those with driving experience of 1-4, 5-9 and 10 yr or more were 0.60, 0.50 and 0.36, respectively. We propose that intensive in-circuit training of learner motorcyclists should replace the conventional on-the-road training on the basis that the former serves to increase their driving experience without subjecting the learner motorcyclists to the risk of sustaining road accident.traffic accident motorcyclist driving experience Singapore

Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation

Emerging evidence indicates that the receptor for growth-hormone–releasing hormone (GHRH-R) is involved in a wide spectrum of extra-pituitary activities, including tumor growth and inflammation. This study elucidates the molecular mechanism of inflammatory processes in acute ocular inflammation mediated by GHRH-R. In human ciliary epithelial cells, the expression of the GHRH-R gene is elevated after lipopolysaccharide insult through the phosphorylation of NF-κB. The activation of GHRH-R stimulates activity of the JAK2/STAT3 pathway, leading to cytokine and chemokine production. In a rat model of endotoxin-induced uveitis, and in human ciliary epithelial cells, antagonists targeting the GHRH-R/JAK2/STAT3–signaling axis alleviate partially the inflammatory responses, supporting a potential therapeutic approach to acute ocular inflammation. Ocular inflammation is a major cause of visual impairment attributed to dysregulation of the immune system. Previously, we have shown that the receptor for growth-hormone–releasing hormone (GHRH-R) affects multiple inflammatory processes. To clarify the pathological roles of GHRH-R in acute ocular inflammation, we investigated the inflammatory cascades mediated by this receptor. In human ciliary epithelial cells, the NF-κB subunit p65 was phosphorylated in response to stimulation with lipopolysaccharide (LPS), resulting in transcriptional up-regulation of GHRH-R. Bioinformatics analysis and coimmunoprecipitation showed that GHRH-R had a direct interaction with JAK2. JAK2, but not JAK1, JAK3, and TYK2, was elevated in ciliary body and iris after treatment with LPS in a rat model of endotoxin-induced uveitis. This elevation augmented the phosphorylation of STAT3 and production of proinflammatory factors, including IL-6, IL-17A, COX2, and iNOS. In explants of iris and ciliary body, the GHRH-R antagonist, MIA-602, suppressed phosphorylation of STAT3 and attenuated expression of downstream proinflammatory factors after LPS treatment. A similar suppression of STAT3 phosphorylation was observed in human ciliary epithelial cells. In vivo studies showed that blocking of the GHRH-R/JAK2/STAT3 axis with the JAK inhibitor Ruxolitinib alleviated partially the LPS-induced acute ocular inflammation by reducing inflammatory cells and protein leakage in the aqueous humor and by repressing expression of STAT3 target genes in rat ciliary body and iris and in human ciliary epithelial cells. Our findings indicate a functional role of the GHRH-R/JAK2/STAT3–signaling axis in acute anterior uveitis and suggest a therapeutic strategy based on treatment with antagonists targeting this signaling pathway