The Next Great Adventure: A Child\u27s Literary Journey through Death and Grief

Literature is often a direct glimpse into another world, conveying messages from characters to help readers shape and define their own futures. Parents and guardians of children are often left searching for a way to use literature to explain the more difficult parts of life to child readers. Grief literature offers models of different grieving processes. Critic Mary Rycik was the first to coin the term bibliotherapy when she discussed the healing role that children\u27s literature played for the traumatized child or young adult. When faced with loss and sorrow, characters will either heal and move on, or succumb to the grief they feel when a loved one dies. The novels in the following thesis: Hans Wilhelm\u27s I \u27ll Always Love You ( 1990), Robert Munsch\u27s Love You Forever ( 1999), Dwight Daniels\u27 Grieving at Christmastime (2005), Ralph L. Klicker\u27s Kolie and the Funeral (2002); S.E. Hinton\u27s The Outsiders ( 1997), Rodman Philbrick\u27s Freak the Mighty ( 1993) Robert Cormier\u27s The Chocolate War ( 1974), and William Golding\u27s Lord of the Flies ( 1954) all showcase characters making both healthy and unhealthy choices regarding grief. Progression plays a pivotal role, for as novels advance in intricacy, readers are presumably advancing in age. Young characters evolve from a reliance on their parents, to friends, and then ultimately decide alone how they want grief to affect them. Grief literature attempts to ready readers of all ages for death and the emotions associated with it. Grief literature offers answers during the tragic times when answers seem scarce. Ultimately death will not be something to be afraid of, but is seen as the great adventure touted by Peter Pan in J.M. Barrie\u27s Peter and Wendy (1911) and Professor Dumbledore in J.K. Rowling\u27s novel, Harry Potter and the Sorcerer \u27s Stone (1997). This is the very goal of grief literature; to turn sorrow into a story, and to turn that story\u27 into life

Natural zeolites and white wines from Campania region (Southern Italy): a new contribution for solving some oenological problems

The purpose of this research is to provide a new mixture of Campanian zeolitized tuffs for solving two specific problems in the production of white wines: the protein and tartaric stability. In fact, a very frequent cause of turbidity and formation of organic deposits in white wines is the occurrence of thermolabile and thermostable proteins colloidal suspensions which precipitate in time, especially in summertime and during the storage and transport. Normally, to mitigate this risk wine producers use organic and inorganic stabilizers and clarifiers. The best known treatment, recognized also by the International Organisation of Vine and Wine (OIV) foresees the use of bentonite with a montmorillonite content not lower than 80%. The present paper aims at evaluating the use of two high zeolite grade Italian volcanoclastites such as the Neapolitan Yellow Tuff (NYT) and the Yellow Facies of the Campanian Ignimbrite (YFCI), in the treatment of three peculiar white wines of the Campanian region (Southern Italy): Falanghina, Fiano di Avellino and Greco di Tufo. Granulates were produced starting from tuff blocks as provided by quarries. Some grain size fractions have been prepared to investigate the zeolite content (phillipsite + chabazite + analcime) by X-ray diffraction (XRD). A 2-5 mm grain size fraction was chosen for NYT and a 5-10 mm for YFCI. Three Campanian monocultivar white wines were used for the test: the Falanghina 2006 vintage, the Fiano di Avellino DOCG 2007 vintage, and the Greco di Tufo DOCG 2008 vintage. 48 samples with mixture of the zeolitized tuffs, 1 sample with mixture of a synthetic zeolite A and 1 sample with mixture of a commercial sodium activated bentonite were prepared. ICP-OES analysis for the determination of ECEC, Ion Chromatography (IC) analyses for the determination of some major cations and Turbidimetric tests for the definition of the protein stabilization process before and after treatments were also carried out. It was evidenced that high zeolitized tuff/wine ratios enable the protein stabilization whereas a significant decrease of potassium ion after the treatment with a zeolite-rich powder improves the tartaric stability, a serious problem in all the wine productions. The results of these tests refer to a laboratory scale research. A transfer of the experiment to a pilot plant scale is in progress

Thin walled pottery from Alife (Northern Campania, Italy)

The file attached is the published version of the article

Knowledge and awareness of autism spectrum disorder among Libyans

Background:  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by the presence of delayed or defective development before the age of three years, as well as behavioral difficulties in social communication and interaction. Objective: To evaluate ASD knowledge and awareness, as well as ASD information sources in a sample of the Libyan general population, and to explore factors that could be associated with the knowledge and awareness. Methods: A cross-sectional study was carried out between 22 March and 13 August 2022 using a self-administered questionnaire. Results: Out of 2195 participants, 48.9% were females and 51.1% were males. Three-quarters of the participants (74.8%) presented a low level of knowledge. Of those whose source of knowledge of autism was social media, 78.9% had a low level of knowledge. However, 57.9% of the participants showed a good level of awareness of autism symptoms and signs. Conclusion: The participants had a limited understanding of the causes and characteristics of ASD. Raising community awareness of the causes and characteristics of ASD is a priority

Gap Junction Mediated Intercellular Metabolite Transfer in the Cochlea Is Compromised in Connexin30 Null Mice

Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co-assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked deafness

BAAV Mediated GJB2 Gene Transfer Restores Gap Junction Coupling in Cochlear Organotypic Cultures from Deaf Cx26Sox10Cre Mice

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26Sox10Cre mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10–Cre line. Cx26Sox10Cre mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26Sox10Cre mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans

High-Density SNP Screening of the Major Histocompatibility Complex in Systemic Lupus Erythematosus Demonstrates Strong Evidence for Independent Susceptibility Regions

A substantial genetic contribution to systemic lupus erythematosus (SLE) risk is conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6p21. Previous studies in SLE have lacked statistical power and genetic resolution to fully define MHC influences. We characterized 1,610 Caucasian SLE cases and 1,470 parents for 1,974 MHC SNPs, the highly polymorphic HLA-DRB1 locus, and a panel of ancestry informative markers. Single-marker analyses revealed strong signals for SNPs within several MHC regions, as well as with HLA-DRB1 (global p = 9.99×10−16). The most strongly associated DRB1 alleles were: *0301 (odds ratio, OR = 2.21, p = 2.53×10−12), *1401 (OR = 0.50, p = 0.0002), and *1501 (OR = 1.39, p = 0.0032). The MHC region SNP demonstrating the strongest evidence of association with SLE was rs3117103, with OR = 2.44 and p = 2.80×10−13. Conditional haplotype and stepwise logistic regression analyses identified strong evidence for association between SLE and the extended class I, class I, class III, class II, and the extended class II MHC regions. Sequential removal of SLE–associated DRB1 haplotypes revealed independent effects due to variation within OR2H2 (extended class I, rs362521, p = 0.006), CREBL1 (class III, rs8283, p = 0.01), and DQB2 (class II, rs7769979, p = 0.003, and rs10947345, p = 0.0004). Further, conditional haplotype analyses demonstrated that variation within MICB (class I, rs3828903, p = 0.006) also contributes to SLE risk independent of HLA-DRB1*0301. Our results for the first time delineate with high resolution several MHC regions with independent contributions to SLE risk. We provide a list of candidate variants based on biologic and functional considerations that may be causally related to SLE risk and warrant further investigation

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council