Immune or at-risk? Stock markets and the significance of the COVID-19 pandemic.

The closure of borders and traditional commerce due to the COVID-19 pandemic is expected to have a lasting financial impact. We determine whether the growth in COVID-19 affected index prices by examining equity markets in five regional epicentres, along with a 'global' index. We also investigate the impact of COVID-19 after controlling for investor sentiment, credit risk, liquidity risk, safe-haven asset demand and the price of oil. Despite controlling for these traditional market drivers, the daily totals of COVID-19 cases nevertheless explained index price changes in Spain, Italy, the United Kingdom and the United States. Similar results were not observed in China, the origin of the virus, nor in the 'global' index (MSCI World). Our results suggest that early interventions (China) and the spatiotemporal nature of pandemic epicentres (World) should be considered by governments, regulators and relevant stakeholders in the event of future COVID-19 'waves' or further extreme societal disruptions.

Periocular dermatitis artefacta in a child.

Dermatitis artifacta is a factitious dermatological disorder with many forms of presentation in any part of the body. It is commonly documented in dermatological cases but rarely presented as an ophthalmic condition. The diagnosis of dermatitis artifacta is often concluded after rigorous and repeated investigation. Histological sampling of skin lesions is usually required in these cases to exclude masquerading skin lesions such as basal cell carcinoma, vasculitis, or herpetic skin lesions.

The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells.

Histamine is an important inflammatory mediator that is released in airways during an asthmatic response. However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses. H4R-deficient mice and mice treated with H4R antagonists exhibited decreased allergic lung inflammation, with decreases in infiltrating lung eosinophils and lymphocytes and decreases in Th2 responses. Ex vivo restimulation of T cells showed decreases in IL-4, IL-5, IL-13, IL-6, and IL-17 levels, suggesting that T cell functions were disrupted. In vitro studies indicated that blockade of the H4R on dendritic cells leads to decreases in cytokine and chemokine production and limits their ability to induce Th2 responses in T cells. This work suggests that the H4R can modulate allergic responses via its influence on T cell activation. The study expands the known influences of histamine on the immune system and highlights the therapeutic potential of H4R antagonists in allergic conditions.

Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis.

Chronic papillary conjunctivitis has been described following adenoviral conjunctivitis. It is unknown however, how long adenovirus is able to persist in the tear film and conjunctiva. To determine if adenovirus persists in the ocular surface following adenoviral conjunctivitis, 304 patients with a history of adenovirus conjunctivitis from whom an adenovirus had been isolated 10 years previously were sent a questionnaire regarding persistent or recurrent symptoms and were invited to attend. Patients were examined and samples of tears and conjunctival cells were collected from both eyes using tear film washes, filter paper, and swabs, the latter for virus isolation. Extracted DNA from the ocular samples was amplified using primers for herpes simplex virus (thymidine kinase) and adenovirus (hexon) genes. Adenovirus amplicons were sequenced and compared to original serotype. Thirty patients attended, 19 of whom had persistent papillary conjunctivitis. Evidence of adenovirus DNA was detected in 17 of 30 patients, 15 of whom also had evidence of a chronic papillary conjunctivitis. Adenovirus DNA was significantly associated with papillary conjunctivitis (P = 0.03). Adenovirus amplicons were successfully sequenced from six patients. Four patients harbored type 3 adenovirus, the same serotype with which they were infected originally 10 years previously. Two patients were infected originally with adenovirus serotype 3 but the current serotype was type 4. Infection of the ocular surface with adenovirus may predispose to the development of a persistent or recurrent conjunctivitis, the presence of which, appears to be associated with evidence of long term persistence of adenovirus DNA.

Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells.

Cellular response to environmental, physiological, or chemical stress is key to survival following injury or disease. Here we describe a unique signaling mechanism by which cells detect and respond to stress in order to survive. A wide variety of stress stimuli rapidly increase nucleocytoplasmic protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of Ser and Thr residues of metazoans. Blocking this post-translational modification, or reducing it, renders cells more sensitive to stress and results in decreased cell survival; and increasing O-GlcNAc levels protects cells. O-GlcNAc regulates both the rates and extent of the stress-induced induction of heat shock proteins, providing a molecular basis for these findings.

Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability.

The Ogt gene encodes a glycosyltransferase that links N-acetylglucosamine to serine and threonine residues (O-GlcNAc) on nuclear and cytosolic proteins. Efforts to study a mammalian model of Ogt deficiency have been hindered by the requirement for this X-linked gene in embryonic stem cell viability, necessitating the use of conditional mutagenesis in vivo. We have extended these observations by segregating Ogt mutation to distinct somatic cell types, including neurons, thymocytes, and fibroblasts, the latter by an approach developed for inducible Ogt mutagenesis. We show that Ogt mutation results in the loss of O-GlcNAc and causes T-cell apoptosis, neuronal tau hyperphosphorylation, and fibroblast growth arrest with altered expression of c-Fos, c-Jun, c-Myc, Sp1, and p27. We further segregated the mutant Ogt allele to parental gametes by oocyte- and spermatid-specific Cre-loxP mutagenesis. By this we established an in vivo genetic approach that supports the ontogeny of female heterozygotes bearing mutant X-linked genes required during embryogenesis. Successful production and characterization of such female heterozygotes further indicates that mammalian cells commonly require a functional Ogt allele. We find that O-GlcNAc modulates protein phosphorylation and expression among essential and conserved cell signaling pathways.

Intracellular glycosylation and development.

O-linked N-acetylglucosamine (O-GlcNAc) is a highly dynamic post-translational modification of cytoplasmic and nuclear proteins. Although the function of this abundant modification is yet to be definitively elucidated, all O-GlcNAc proteins are phosphoproteins. Further, the serine and threonine residues substituted with O-GlcNAc are often sites of, or close to sites of, protein phosphorylation. This implies that there may be a dynamic interplay between these two post-translational modifications to regulate protein function. In this review, the functions of some of the proteins that are modified by O-GlcNAc will be considered in the context of the potential role of the O-GlcNAc modification. Furthermore, predictions will be made as to how cellular function and developmental regulation might be affected by changes in O-GlcNAc levels.

Occlusion therapy for the treatment of amblyopia: letting the parents decide.

BACKGROUND: Compliance with prescribed occlusion therapy is a significant problem in the treatment of amblyopia. Parental preference for a particular type of occlusion treatment has not been previously addressed. Unless parental views are taken into account when planning therapy, compliance may be poor and treatment may fail. SUBJECTS AND METHODS: Parents of children with strabismic and/or anisometropic amblyopia who were due to start or had already had occlusion treatment were included in this study. Group A comprised parents of children who had no previous experience of occlusion, and group B comprised parents of children who had previous experience of occlusion therapy. Parental preferences regarding occlusion therapy were investigated by way of a questionnaire, in which they were asked whether they would prefer part-day/full-week occlusion or all-day/part-week occlusion so that the total number of hours of occlusion per week was the same. RESULTS: One hundred parents completed the questionnaire, 47 from group A and 53 from group B. A significant number of parents in group A (95.3%) who had no previous experience with occlusion preferred part-day/full-week occlusion (p < 0.001), whereas there was no such preference among parents who had experience with occlusion, that is only 54.3% of parents in group B showed a preference for part-day/full-week occlusion (p = 0.1). The reasons given by the parents for their preferences varied but were in keeping with their lifestyles so that the type of occlusion regimen chosen by the parents was in accordance with the reasons given for their choice. CONCLUSION: Parental preferences should be considered when occlusion therapy is planned if compliance is to be improved. For maintenance occlusion, it would be reasonable to prescribe the number of hours of occlusion required per week and allow parents the responsibility to implement the pattern of occlusion according to their circumstances--the implied restriction ensuring that the number of hours of occlusion per week is met. Although parents appeared to have preconceived ideas before the commencement of treatment, their preferences changed once treatment had begun.