Meningococcal Meningitis

Meningococcal disease may present as meningitis, septicemia, or a combination of the two. Generally, meningitis has a gradual onset, with fever, headache, and neck stiffness as the most frequent clinical symptoms. By contrast, fulminant septicemia may develop within hours, and is characterized by petechial bleedings and shock. It is of vital importance to diagnose and treat meningococcal disease rapidly. The diagnosis is based on the culture of Neisseria meningitides from blood or cerebrospinal fluid, or on the polymerase chain reaction (PCR) of spinal fluid. Cefotaxime or ceftriaxone are usually recommended as antibacterial treatment. There is a vaccine effective against disease with serogroups A, C, Y, and W

Clinically Relevant Biomarker Discovery in High-Risk Recurrent Neuroblastoma

Source at https://doi.org/10.1177/1176935119832910.Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system. High-risk neuroblastoma patients typically undergo an initial remission in response to treatment, followed by recurrence of aggressive tumors that have become refractory to further treatment. The need for biomarkers that can select patients not responding well to therapy in an early phase is therefore needed. In this study, we used next generation sequencing technology to determine the expression profiles in high-risk neuroblastoma cell lines established before and after therapy. Using partial least squares-discriminant analysis (PLS-DA) with least absolute shrinkage and selection operator (LASSO) and leave-one-out cross-validation, we identified a panel of 55 messenger RNAs and 17 long non-coding RNAs (lncRNAs) which were significantly altered in the expression between cell lines isolated from primary and recurrent tumors. From a neuroblastoma patient cohort, we found 20 of the 55 protein-coding genes to be differentially expressed in patients with unfavorable compared with favorable outcome. We further found a twofold increase or decrease in hazard ratios in these genes when comparing patients with unfavorable and favorable outcome. Gene set enrichment analysis (GSEA) revealed that these genes were involved in proliferation, differentiation and regulated by Polycomb group (PcG) proteins. Of the 17 lncRNAs, 3 upregulated (NEAT1, SH3BP5-AS1, NORAD) and 3 downregulated lncRNAs (DUBR, MEG3, DHRS4-AS1) were also found to be differentially expressed in favorable compared with unfavorable outcome. Moreover, using expression profiles on both miRNAs and mRNAs in the same cohort of cell lines, we found 13 downregulated and 18 upregulated experimentally observed miRNA target genes targeted by miR-21, -424 and -30e, -29b, -138, -494, -181a, -34a, -29b, respectively. The advantage of analyzing biomarkers in a clinically relevant neuroblastoma model system enables further studies on the effect of individual genes upon gene perturbation. In summary, this study identified several genes, which may aid in the prediction of response to therapy and tumor recurrence

High prevalence of overweight and obesity among 6-year-old children in Finnmark County, North Norway

This is the peer reviewed version of the following article: Kokkvoll, A., Jeppesen, E., Juliusson, P. B., Flægstad, T. and Njølstad, I. (2012), High prevalence of overweight and obesity among 6-year-old children in Finnmark County, North Norway. Acta Paediatrica, 101: 924–928, which has been published in final form at http://dx.doi.org/10.1111/j.1651-2227.2012.02735.x. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archivingAim:  The aim was to determine the prevalence of overweight and obesity among 6-year-old children in Finnmark, the northernmost county of Norway. Methods:  This is a survey of 1774 children born during 1999 and 2000 from 18 of 19 child healthcare centres in Finnmark. Body mass index data extracted retrospectively in 2007 from health records at the age of 6 years were compared with international definitions of over- and underweight. The prevalence figures were further compared with socio-demographic figures on municipality level. Results:  Overall, 19% of the children were classified as overweight or obese; 5% were classified as obese. The prevalence of overweight and obesity was higher among girls (22%) than among boys (16%) (p < 0.01). The prevalence of underweight was 8% among both girls and boys. Despite large variations in the prevalence of overweight and obesity between municipalities (9–35%), no association was found with municipality figures on socio-demographic factors. Conclusion:  In the northernmost county Finnmark, the prevalence of overweight including obesity among 6-year-old children was somewhat higher than in previous surveys from Norway, especially among girls.acceptedVersio

Comparison of RNAi efficiency mediated by tetracycline-responsive H1 and U6 promoter variants in mammalian cell lines

Conditional expression of short hairpin RNAs (shRNAs) to knock down target genes is a powerful tool to study gene function. The most common inducible expression systems are based on tetracycline-regulated RNA polymerase III promoters. During the last years, several tetracycline-inducible U6 and H1 promoter variants have been reported in different experimental settings showing variable efficiencies. In this study, we compare the most common variants of these promoters in several mammalian cell lines. For all cell lines tested, we find that several inducible U6 and H1 promoters containing single tetracycline operator (tetO) sequences show high-transcriptional background in the non-induced state. Promoter variants containing two tetO sequences show tight suppression of transcription in the non-induced state, and high tet responsiveness and high gene knockdown efficiency upon induction in all cell lines tested. We report a variant of the H1 promoter containing two O2-type tetO sequences flanking the TATA box that shows little transcriptional background in the non-induced state and up to 90% target knockdown when the inducer molecule (dox–doxycycline) is added. This inducible system for RNAi-based gene silencing is a good candidate for use both in basic research on gene function and for potential therapeutic applications

Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma

BACKGROUND: MicroRNAs (miRNAs) regulate expression of many cancer-related genes through posttranscriptional repression of their mRNAs. In this study we investigate the proto-oncogene MYCN as a target for miRNA regulation. METHODS: A luciferase reporter assay was used to investigate software-predicted miRNA target sites in the 30 -untranslated region (30 UTR) of MYCN. The miRNAs were overexpressed in cell lines by transfection of miRNA mimics or miRNA-expressing plasmids. Mutation of the target sites was used to validate MYCN 30 UTR as a direct target of several miRNAs. To measure miRNA-mediated suppression of endogenous N-myc protein, inhibition of proliferation and inhibition of clonogenic growth, miRNAs were overexpressed in a MYCN-amplified neuroblastoma cell line. RESULTS: The results from this study show that MYCN is targeted by several miRNAs. In addition to the previously shown mir-34a/c, we experimentally validate mir-449, mir-19a/b, mir-29a/b/c, mir-101 and let-7e/mir-202 as direct MYCN-targeting miRNAs. These miRNAs were able to suppress endogenous N-myc protein in a MYCN-amplified neuroblastoma cell line. The let-7e and mir-202 were strong negative regulators of MYCN expression. The mir-101 and the let-7 family miRNAs let-7e and mir-202 inhibited proliferation and clonogenic growth when overexpressed in Kelly cells. CONCLUSION: The tumour-suppressor miRNAs let-7 and mir-101 target MYCN and inhibit proliferation and clonogenic growth of MYCN-amplified neuroblastoma cells

An integrated transcriptome analysis in T-cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated TAL1 and ANTP homeobox gene expression

Classification of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T-ALL patients were characterized by genome-wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P <0.001) and mitotic age (P <0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2-1, and novel genes in T-ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP- subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL-TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP-), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T-ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.Peer reviewe

Comunicazione italiana nel mondo: interviste a distanza. Prove d'Europa a Radio Colonia

L’Europa è di casa a Radio Colonia, l’emittente italiana del WDR, Westdeutscher Rundfunk, l’ente radiotelevisivo pubblico del Land Nord Reno-Westfalia, che il primo dicembre scorso ha celebrato il mezzo secolo di vita. Il suo direttore, Tommaso Pedicini, ricorda i motivi che portarono alla nascita della Radio, nel 1961, in un periodo in cui esplodeva il fenomeno dell’emigrazione italiana in Germania ed i Gastarbeiter (“lavoratori ospiti”) italiani avevano bisogno di una voce amica. Da allora molti sono stati i cambiamenti, ma Radio Colonia è rimasta la finestra italiana nel panorama radiofonico tedesco, impegnata in particolare, dopo l’avvio nel 1999 della Funkhaus Europa, a coltivare i temi del plurilinguismo e dell’integrazione degli immigrati

Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe.

OBJECTIVE: To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. METHODS: Children (0-19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. RESULTS: A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p<0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p=0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. CONCLUSIONS: Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study

The Norwegian childhood cancer biobank

Background - The rapidly expanding era of “omics” research is highly dependent on the availability of quality-proven biological material, especially for rare conditions such as pediatric malignancies. Professional biobanks provide such material, focusing on standardized collection and handling procedures, distinctive quality measurements, traceability of storage conditions, and accessibility. For pediatric malignancies, traditional tumor biobanking is challenging due to the rareness and limited amount of tissue and blood samples. The higher molecular heterogeneity, lower mutation rates, and unique genomic landscapes, however, renders biobanking of this tissue even more crucial. Aim - The aim of this study was to test and establish methods for a prospective and centralized biobank for infants, children, and adolescents up to 18 years of age diagnosed with cancer in Norway. Methods - Obtain judicial and ethical approvals and administration through a consortium, steering committee, and advisory board. Develop pipelines including SOPs for all aspects in the biobank process, including collection, processing and storing of samples and data, as well of quality controlling, safeguarding, distributing, and transport. Results - The childhood cancer biobanking started at Oslo University Hospital in March 2017 and was from 2019 run as a national Norwegian Childhood Cancer Biobank. Informed consent and biological samples are collected regionally and stored centrally. Approximately 12 000 samples from 510 patients and have been included by January 1, 2021, representing a 96% consent and participation rate among our newly diagnosed patients. Conclusion - A well-functioning nationwide collection and centralized biobank with standardized procedures and national storage for pediatric malignancies has been established with a high acceptance among families

Chronic iron deficiency and anaemia were highly prevalent in a population-based longitudinal study among adolescent girls

Aim: The combination of iron deficiency and anaemia is a major health problem, and adolescents are an at- risk group. The main aim of this study was to explore the mag-nitude of these conditions among adolescents aged 15–19 and identify possible as-sociated risk factors. Methods: This population- based longitudinal study of adolescents in North Norway was conducted in 2010–2011, with a follow-up two years later. Repeated measure-ments of iron deficiency and anaemia and its possible risk factors were studied in 309 girls and 273 boys. Results: Iron deficiency and anaemia were found in 18.1% and 19.9% of girls and 1.6% and 2.9% of boys in the first study and about half of the cases were chronic two years later. Most girls had moderate iron deficiency (14.5%) and mild anaemia (16.0%). Daily milk consumption was associated with increased iron deficiency in girls (odds ratio 2.3, 95% confidence interval 1.1–4.9), and the most physically active girls had the lowest levels of iron deficiency (odds ratio 0.4, 95% confidence intervaI 0.2–0.9). Iron deficiency was the most important risk factor for chronic anaemia in girls. Conclusion: The results of this study highlight the importance of iron deficiency screening and treatment for adolescent girls