Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice

PurposeWe aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis.MethodsWe administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements.ResultsPollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4⁺ T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo.ConclusionsOur results indicate the non-redundant roles for the allergens’ particulate properties and soluble factors in the development of allergic conjunctivitis.     

The associations between state veteran population rates,handgun legislation,and statewide suicide rates

BackgroundWithin the US, veterans exhibit an elevated suicide rate, with firearms serving as the most common method. Research has demonstrated that several state laws regulating handgun ownership are associated with lower suicide rates.MethodPublically available databases were utilized to extract relevant data.ResultsStatewide veteran population rates (per 100,000) predicted overall suicide rates, firearm suicide rates, and the proportion of suicides by firearms. Furthermore, the association between veteran population and overall suicide rate was largely explained by the elevated proportion of suicides by firearms in states with higher veteran populations. Lastly, results demonstrated states without handgun legislation in place exhibited higher veteran populations.ConclusionsFindings indicate veterans may impact statewide suicide rates through their propensity to use firearms as their method and that the tendency for veterans to live in states without handgun legislation may exacerbate this phenomenon.     

Impaired GSH biosynthesis disrupts eye development,lens morphogenesis and PAX6 function

PurposeThe purpose of this study was to elucidate the role and molecular consequences of impaired glutathione (GSH) biosynthesis on eye development.MethodsGSH biosynthesis was impaired in surface ectoderm-derived ocular tissues by crossing Gclc^f/f mice with hemizygous Le-Cre transgenic mice to produce Gclc^f/f/Le-Cre^Tg/- (KO) mice. Control mice included Gclc^f/f and Gclc^wt/wt/Le-Cre^Tg/- mice (CRE). Eyes from all mice (at various stages of eye development) were subjected to histological, immunohistochemical, Western blot, RT-qPCR, RNA-seq, and subsequent Gene Ontology, Ingenuity Pathway Analysis and TRANSFAC analyses. PAX6 transactivation activity was studied using a luciferase reporter assay in HEK293T cells depleted of GSH using buthionine sulfoximine (BSO).ResultsDeletion of Gclc diminished GSH levels, increased reactive oxygen species (ROS), and caused an overt microphthalmia phenotype characterized by malformation of the cornea, iris, lens, and retina that is distinct from and much more profound than the one observed in CRE mice. In addition, only the lenses of KO mice displayed reduced crystallin (α, β), PITX3 and Foxe3 expression. RNA-seq analyses at postnatal day 1 revealed 1552 differentially expressed genes (DEGs) in the lenses of KO mice relative to those from Gclc^f/f mice, with Crystallin and lens fiber cell identity genes being downregulated while lens epithelial cell identity and immune response genes were upregulated. Bioinformatic analysis of the DEGs implicated PAX6 as a key upstream regulator. PAX6 transactivation activity was impaired in BSO-treated HEK293T cells.ConclusionsThese data suggest that impaired ocular GSH biosynthesis may disrupt eye development and PAX6 function.     

Intratympanic corticosteroid for Bell's palsy and Ramsay Hunt syndrome: Systematic review and meta-analysis

ObjectiveThis study aimed to reveal the efficacy and safety of intratympanic steroid therapy (ITST) in patients with Bell's palsy and Ramsay Hunt syndrome.MethodsA literature search was conducted in PubMed, Embase, Ichushi-Web, and Cochrane Central Register of Controlled Trials. Published randomized controlled trial and observational studies, which compared the combination of intratympanic corticosteroids with systemic corticosteroid versus systemic corticosteroid for Bell's palsy and Ramsay Hunt syndrome, were included for meta-analysis. The primary outcome was non-recovery at the end of the study follow-up. Data was analyzed using Review Manager software, and pooled odds ratio with 95% CI were calculated.ResultsThree randomized controlled trial and two cohort studies met the eligible criteria, and 350 individuals included for meta-analysis. The timing of intratympanic corticosteroid was varied from once or twice a week to consecutive 10-days. Patients treated with combination of systemic corticosteroids and intratympanic corticosteroids were likely to achieve recovery of normal facial function (OR = 0.36 [95% CI 0.12–1.14]). The subgroup analysis of the timing revealed that daily ITST reduced non-recovery (OR = 0.14 [95% CI 0.04-0.50). However, non-daily ITST did not reduced non-recovery (OR 0.93 [95% CI 0.37-2.34]).ConclusionIntratympanic corticosteroid have a potential to reduce non-recovery in patients with Bell's palsy and Ramsay Hunt syndrome. The methods of intratympanic corticosteroid varied among included studies. Further well-designed randomized controlled trial is needed to confirm the effectiveness and to identify an adequate method of intratympanic corticosteroid in these patients.     

Prediabetes diagnosis criteria,type 2 diabetes risk and dietary modulation: The CORDIOPREV study

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