Transient Neonatal Diabetes Mellitus in a Very Preterm Infant due to ABCC8 Mutation

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring within 6 months from birth. NDM can be permanent or transient (TNDM). We report the case of a preterm infant with TNDM due to an ABCC8 mutation identified by next-generation sequencing. The pancreatic adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channel is a key regulator of insulin secretion. Gain-of-function mutations in the genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the channel cause neonatal diabetes. The patient was successfully managed with insulin lispro at a 1:100 dilution, drawn up in an insulin pen injector with a 4-mm needle. The insulin lispro dilution allowed administration of the exact insulin doses, obtaining a good glycemic control and minimizing the burden of injections. At 2 months, corrected age insulin doses were progressively decreased until discontinuation

From Inscriptions to Lexica and Back: A Platform for Editing and Linking the Languages of Ancient Italy

Available language technology is hardly applicable to scarcely attested ancient languages, yet their digital semantic representation, though challenging, is an asset for the purpose of sharing and preserving existing cultural knowledge. In the context of a project on the languages and cultures of ancient Italy, we took up this challenge. This paper thus describes the development of a user friendly web platform, EpiLexO, for the creation and editing of an integrated system of language resources for ancient fragmentary languages centered on the lexicon, in compliance with current digital humanities and Linked Open Data principles. EpiLexo allows for the editing of lexica with all relevant cross-references: for their linking to their testimonies, as well as to bibliographic information and other (external) resources and common vocabularies. The focus of the current implementation is on the languages of ancient Italy, in particular Oscan, Faliscan, Celtic and Venetic; however, the technological solutions are designed to be general enough to be potentially applicable to different contexts and scenarios

The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations

Antibodies elicited by a triple homologous or heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1.The SARS-CoV-2 Omicron variant has rapidly replaced the Delta variant of concern. This new variant harbors worrisome mutations on the spike protein, which are able to escape the immunity elicited by vaccination and/or natural infection. To evaluate the impact and susceptibility of different serum samples to the Omicron variant BA.1, samples from COVID-19 patients and vaccinated individuals were tested for their ability to bind and neutralize the original SARS-CoV-2 virus and the Omicron variant BA.1. COVID-19 patients show the most drastic reduction in Omicron-specific antibody response in comparison with the response to the wild-type virus. Antibodies elicited by a triple homologous/heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1. Overall, these findings confirm that vaccination of COVID-19 survivors and booster dose to vaccinees with mRNA vaccines is the correct strategy to enhance the antibody cross-protection against Omicron variant BA.1

The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022

Context In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM).Objective To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS).Methods We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset.Results Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin.Conclusion NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Ponatinib alone or with chemo-immunotherapy in heavily pre-treated Philadelphia-like acute lymphoblastic leukemia: a CAMPUS ALL real-life study

Not available

A Probe into the Reform of Public Calligraphy Course in Chinese Colleges and Universities

中国书法是中国传统文化中的瑰宝，它既是一门艺术，又有着深厚的文化内涵。我国普通高校开设公共书法教学是与目前倡导的素质教育，培养创新型人才，提倡人的全面和谐发展的高等教育理念相一致的。加强高校公共书法教育，是全面推进素质教育的有效途径之一，也是提高当代大学生人文素质的重要手段。它对促进大学生人格完善、创造力培养以及民族文化的传承等有着不可低估的作用。本文主要针对我国普通高等院校公共书法教学现状进行分析，并由此比较借鉴日本高校中实施书法教学的成功经验提出对我国高校公共书法教学改革的具体建议和措施，设计并实践一种具备学科视野的、以学生为主体的公共书法教学的新模式。论文共分为五部分。引言扼要介绍论文写...Chinese calligraphy is a treasure of Chinese traditional culture. It not only is an art, but also has profound culture contents. Opening the public calligraphy course to the university students is in accordance with the concept that advocated by the current quality- oriented education, which aims to cultivate the students’ creative talent and comprehensive development. This paper concentrates on a...学位：文学硕士院系专业：艺术教育学院美术系_美术学学号：20042201