Cardiac outcomes in severe acute respiratory syndrome coronavirus-2-associated multisystem inflammatory syndrome at a tertiary paediatric hospital

INTRODUCTION: We describe a cohort of children referred with multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 and compare this cohort with a 2019 cohort of children with Kawasaki disease. METHODS: We conducted a retrospective cohort study of 2019 and 2020 referrals to the inflammatory cardiology service at Great Ormond Street Hospital for Children. We compared cardiac and inflammatory parameters of a sub-section of the 2020 cohort who presented with reduced left ventricular ejection fraction with the remainder of the cohort. RESULTS: Referrals significantly increased between February and June 2020 compared to 2019 (19.8/30 days versus 3.9/30 days). Frequency of coronary artery aneurysms (11/79 (13.9%) versus 7/47 (14.9%)) or severe coronary artery aneurysms (6/79 (7.6%) versus 3/47 (6.4%)) was similar between 2020 and 2019, respectively. The 2020 cohort was older (median age 9.07 years versus 2.38 years), more likely to be of Black, Asian, or other minority ethnic group (60/76 (78.9%) versus 25/42 (59.5%)), and more likely to require inotropic support (22 (27.5%) versus 0 (0%)). Even children with significantly reduced left ventricular ejection fraction demonstrated complete recovery of cardiac function within 10 days (mean 5.25 days ± 2.7). DISCUSSION: We observed complete recovery of myocardial dysfunction and an overall low rate of permanent coronary sequelae, indicating that the majority of children with multisystem inflammatory syndrome in children are unlikely to encounter long-term cardiac morbidity. Although the frequency of myocardial dysfunction and inotropic support requirement is not consistent with a diagnosis of Kawasaki disease, the frequency of coronary artery abnormalities and severe coronary artery abnormalities suggests a degree of phenotypic overlap

Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice

1,3-Butadiene (BD), a widely used industrial chemical and a ubiquitous environmental pollutant, is a known human carcinogen. Although genotoxicity is an established mechanism of the tumorigenicity of BD, epigenetic effects have also been observed in livers of mice exposed to the chemical. To better characterize the diverse molecular mechanisms of BD tumorigenicity, we evaluated genotoxic and epigenotoxic effects of BD exposure in mouse tissues that are target (lung and liver) and non-target (kidney) for BD-induced tumors. We hypothesized that epigenetic alterations may explain, at least in part, the tissue-specific differences in BD tumorigenicity in mice. We evaluated the level of N-7-(2,3,4-trihydroxybut-1-yl)guanine adducts and 1,4-bis-(guan-7-yl)-2,3-butanediol crosslinks, DNA methylation, and histone modifications in male C57BL/6 mice exposed to filtered air or 425 ppm of BD by inhalation (6 h/day, 5 days/week) for 2 weeks. Although DNA damage was observed in all three tissues of BD-exposed mice, variation in epigenetic effects clearly existed between the kidneys, liver, and lungs. Epigenetic alterations indicative of genomic instability, including demethylation of repetitive DNA sequences and alterations in histone-lysine acetylation, were evident in the liver and lung tissues of BD-exposed mice. Changes in DNA methylation were insignificant in the kidneys of treated mice, whereas marks of condensed heterochromatin and transcriptional silencing (histone-lysine trimethylation) were increased. These modifications may represent a potential mechanistic explanation for the lack of tumorigenesis in the kidney. Our results indicate that differential tissue susceptibility to chemical-induced tumorigenesis may be attributed to tissue-specific epigenetic alterations

Gastrointestinal presentation of kawasaki disease: A red flag for severe disease?

Background Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. Objective To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. Methods Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. Results 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). Conclusions This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population

Multiprobiotic therapy from childhood prevents the development of nonalcoholic fatty liver disease in adult monosodium glutamate-induced obese rats

Considering the association between microflora and obesity, and the significantly higher prevalence of non-alcoholic fatty liver disease (NAFLD) in obese people, the aim of our study was to investigate the preventive effect of multiprobiotics on the monosodium glutamate (MSG) induced NAFLD model, in rats. The work was carried out on 60 rats placed into three groups: the Control group, the MSG-group and the MSG-probiotic group. The MSG-group and the MSG-probiotic group were injected with 4 mg/g of MSG subcutaneously neonatally on the 2nd-10th days of life. The MSG-probiotic rats were also treated with 140 mg/kg of multiprobiotic “Symbiter” from the 4th week of life. In the 4-month-old rats, biochemical and morphological changes in liver were assessed, and steatosis was confirmed by the NAFLD activity score (NAS). Our results reveal that the multiprobiotic lowered total NAS, the degree of steatosis and the liver lobular inflammation caused by MSG. It also brought about decreased liver total lipids and triglycerids content, as well as decreased visceral adipose tissue mass. However, there was no difference in the liver serum biochemical indicators between all experimental groups. The obtained data does suggest the efficacy of probiotics in the prevention of NAFLD

Застосування електронних засобів у тестуванні координаційної витривалості студентів з інвалідністю – ветеранів війни

The purpose of the study was to determine the effectiveness of the use of electronic means created based on information and communication technologies in coordination testing of the endurance of students with disabilities who are war veterans in practical physical education classes. Materials and methods. To solve research problems, scientific intelligence applied the implementation of research at the theoretical and empirical levels. Analysis, synthesis, generalization, induction, systematization, pedagogical experiment, methods of mathematical statistics and technical modeling were used. The study involved 46 students who are war veterans (males aged 17–18). Results. An electronic mean for determining coordination endurance based on information and communication technologies and software has been developed. The design of the mean involves the use of mobile and stationary measuring units and a personal computer. The measuring unit contains analog and digital sensors. Information about the student’s performance on the test is displayed on the personal computer screen. Approbation of the developed mean involved establishing the degree of its authenticity by comparing the results of testing the coordination endurance of students with disabilities who are war veterans implemented using traditional methods of measurement and the results of testing using the developed mean. The calculation of the reliability and validity of the tests showed that the recording of control results by electronic means allows ensuring a high level of authenticity of the tests. Conclusions. The use of the electronic control means of coordination endurance presented in the work allows the achievement of a high level of reliability of control results in real time. Based on the summaries of the conducted empirical research, it was established that the introduction of electronic means of control in the process of physical education of students with disabilities who are war veterans helps to ensure the effectiveness of this process.Мета дослідження – полягає у визначенні ефективності використання електронних засобів, створених на основі інформаційно-комунікаційних технологій, у тестуванні координаційної витривалості студентів з інвалідністю ветеранів війни у їхньому фізичному вихованні. Матеріали та методи. Для вирішення дослідницьких завдань наукової розвідки, дослідження реалізовано на теоретичному та емпіричному рівнях. Використано аналіз, синтез, узагальнення, індукція, систематизація, педагогічний експеримент, методи математичної статистики та технічного моделювання. У дослідженні взяли участь 46 студентів – ветеранів війни (чоловіки 29-35 років). Результати. Розроблено електронний засіб для визначення координаційної витривалості на основі інформаційно- комунікаційних технологій та програмного забезпечення. Конструкція засобу передбачає використання мобільного та стаціонарного вимірювальних блоків та персонального комп’ютера. Вимірювальний блок містить аналогові та цифрові сенсори. Інформація про виконання тесту студентом подається на екран персонального комп’ютера. Апробація розро- бленого пристрою передбачала установлення ступеня його автентичності, шляхом порівняння результатів тестування координаційної витривалості виховання студентів з інвалідністю – ветеранів війни реалізованого з використанням педагогічних тестів та тестування з використанням розробленого засобу контролю. Обчислення надійності та валідності тестів показало, що фіксація результатів контролю електронним засобом дозволяє забезпечити високий рівень автентичності тестів. Висновки. Використання представленого у роботі електронного засобу контролю координаційної витривалості дозволяє досягти високого рівня достовірності результатів контролю в режимі реального часу. На підставі підсумків проведеного емпіричного дослідження встановлено, що впровадження електронних засобів контролю в процес фізичного виховання студентів з інвалідністю – ветеранів війни сприяє забезпеченню ефективності цього процесу

Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice

1,3-Butadiene (BD), a widely used industrial chemical and a ubiquitous environmental pollutant, is a known human carcinogen. Although genotoxicity is an established mechanism of the tumorigenicity of BD, epigenetic effects have also been observed in livers of mice exposed to the chemical. To better characterize the diverse molecular mechanisms of BD tumorigenicity, we evaluated genotoxic and epigenotoxic effects of BD exposure in mouse tissues that are target (lung and liver) and non-target (kidney) for BD-induced tumors. We hypothesized that epigenetic alterations may explain, at least in part, the tissue-specific differences in BD tumorigenicity in mice. We evaluated the level of N-7-(2,3,4-trihydroxybut-1-yl)guanine adducts and 1,4-bis-(guan-7-yl)-2,3-butanediol crosslinks, DNA methylation, and histone modifications in male C57BL/6 mice exposed to filtered air or 425 ppm of BD by inhalation (6 h/day, 5 days/week) for 2 weeks. Although DNA damage was observed in all three tissues of BD-exposed mice, variation in epigenetic effects clearly existed between the kidneys, liver, and lungs. Epigenetic alterations indicative of genomic instability, including demethylation of repetitive DNA sequences and alterations in histone-lysine acetylation, were evident in the liver and lung tissues of BD-exposed mice. Changes in DNA methylation were insignificant in the kidneys of treated mice, whereas marks of condensed heterochromatin and transcriptional silencing (histone-lysine trimethylation) were increased. These modifications may represent a potential mechanistic explanation for the lack of tumorigenesis in the kidney. Our results indicate that differential tissue susceptibility to chemical-induced tumorigenesis may be attributed to tissue-specific epigenetic alterations

Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor. Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment.What is Known:\u2022 There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions.\u2022 Data are scarce on their effectiveness in non-Asian children.What is New:\u2022 We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement.\u2022 Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities