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Aim: Multisystem inflammatory syndrome in children (MIS‐C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS‐C in 25 different hospitals in Turkey. Methods: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. Results: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6–9.3); 51 (50.5%) were boys. Reverse‐transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS‐CoV‐2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C‐reactive protein (in 101 patients, median 165 mg/L; range 112–228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30–84) and procalcitonin levels (86/89, median 5 μg/L; IQR 0.58–20.2) were elevated. Thirty‐eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. Conclusion: The clinical spectrum of MIS‐C is broad, but clinicians should consider MIS‐C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS‐C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS‐C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS‐C. Prompt diagnosis and prompt treatment are essential for optimal management. [ABSTRACT FROM AUTHOR]

Although Crimean‐Congo hemorrhagic fever (CCHF) is mild and self‐limited in children, some patients may develop excessive bleeding, massive liver necrosis, and multiple organ failure associated with secondary hemophagocytic lymphohistiocytosis (HLH) induced by cytokine storm. Treatment of CCHF is mainly symptomatic and supportive. The efficacy of ribavirin, which is the only antiviral drug in the treatment of CCHF, remains controversial. Although therapeutic plasma exchange (TPE) has been shown to beneficial in small case series with primary and secondary HLH, there is no pediatric patient with HLH secondary to CCHF treated with TPE in the literature. In this report, we describe the first pediatric patient who was successfully recovered from HLH secondary to CCHF with ribavirin, intravenous immunoglobulin, and TPE. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a highly (60‐80%) heritable disease with 75 known genetic risk loci. Interestingly, preliminary data from human tissues suggests that these risk loci predominantly act through myeloid cells, implicating microglia, the brain's resident immune cell, as playing a critical role in AD risk. However, whether the mechanisms underlying these risk loci can be studied in induced pluripotent stem cell (iPSC)‐derived systems, which are currently the only physiologically relevant human model system, remains unknown. Method: We generated neural progenitors, excitatory neurons, astrocytes and microglia from two human iPSC lines, and performed RNA‐seq to identify all expressed genes and ChIP‐seq for H3K27ac to identify all active gene promoters and enhancers. We compared these data to ChIP‐seq data from primary uncultured (ex vivo) adult human microglia to compare the enrichment of AD risk loci polymorphisms in active promoters and enhancers, as well as a larger panel of neuropsychiatric and neurodegenerative conditions. Result: iPSC‐derived microglia‐like cells (iMGLs) recapitulated an enrichment of AD risk loci polymorphisms in microglial promoters and enhancers previously seen in ex vivo primary human microglia. Furthermore, the enrichments of polymorphisms conferring risk for other neurological and neurodegenerative conditions were similar in iMGLs and ex vivo microglia, suggesting that the epigenome of iMGLs is similar to that of in vivo human microglia. Conclusion: iMGLs will serve as a useful cell‐based model for studying AD risk loci, and we are currently developing high‐throughput CRISPR‐based genome and epigenome editing systems to dissect the molecular and cellular mechanisms at these loci, which will nominate novel genes and pathways for therapeutic development. [ABSTRACT FROM AUTHOR]

In this study, we investigated gene delivery properties of Jeffamine-cored polyamidoamine (PAMAM) dendrimers (JCPDs). The effects of dendrimer concentration, generation, and core size on the gene delivery have been analyzed. The experimental results showed that the JCPD effectively delivered plasmid DNA inside the HeLa cells, and the transfection efficiency improved considerably as the number of generation increased. The cytotoxicity of JCPD in different concentration was tested for HeLa cell line. JCPD was complexed with a lacZ gene carrying plasmid and tested for transfection efficiency using quantitative β-galactosidase expression assay. Additionally, confocal microscopy results revealed that JCPD effectively delivered green fluorescent protein-expressing plasmid into HeLa cells and produced fluorescent signal with satisfactory efficiency. The highest transfection efficiency was obtained from JCPDs G4 and G5, which mixed with expression plasmid vectors at a 10/1 weight ratio. These results indicated that under optimized conditions, JCPD can be considered as an efficient transfection reagent and can be effectively used for gene delivery applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2623-2628, 2012. [ABSTRACT FROM AUTHOR]

A fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered although it could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform, and this has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about inter‐individual transcriptional variability in multicellular organisms. Using transcriptomic approaches, we analysed gene expression variability between individual Arabidopsis thaliana plants growing in identical conditions over a 24‐h time course. We identified hundreds of genes that exhibit high inter‐individual variability and found that many are involved in environmental responses, with different classes of genes variable between the day and night. We also identified factors that might facilitate gene expression variability, such as gene length, the number of transcription factors regulating the genes and the chromatin environment. These results shed new light on the impact of transcriptional variability in gene expression regulation in plants. Synopsis: RNA‐seq on individual seedlings is used to detect inter‐individual gene expression variability in Arabidopsis thaliana. 9% of the transcriptome is identified as highly variable for at least one time point during the day/night cycle. Two sets of highly variable genes were identified, either mainly variable during the day or night.Highly variable genes tend to be involved in the response to the environment.Highly variable genes tend to be shorter, to be targeted by a higher number of transcription factors and to be characterised by a "closed" chromatin environment.Gene expression variability for individual genes of interest can be viewed on https://jlgroup.shinyapps.io/AraNoisy/. RNA‐seq on individual seedlings is used to detect inter‐individual gene expression variability in Arabidopsis thaliana. 9% of the transcriptome is identified as highly variable for at least one time point during the day/night cycle. [ABSTRACT FROM AUTHOR]