Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics

A non-interventional, prospective, multicenter study for evaluation of the use of the herbal medicinal product Canephron® N in the pediatric outpatient population in Russia

Abstract Background A herbal medicinal product (HMP) with centaury, lovage, and rosemary as active ingredients (brand name: Canephron® N) has been widely used for treatment and prevention of urinary tract infections (UTIs) and other urinary system disorders. Non-clinical in vitro and in vivo data indicate its diuretic, spasmolytic, anti-inflammatory, antioxidative and analgesic effects. The purpose of this non-interventional, prospective, multicenter study was to collect data on the use of the HMP in the Russian pediatric outpatient population. Results In total, 636 outpatients aged 1–17 years were enrolled. Of these, 634 received at least one dose of the HMP and were included in the safety set, which was used for analysis. 61 patients were 12–23 months, 227 were 2–5 years, 234 were 6–11 years and 112 were 12–17 years of age. The oral solution of the HMP was prescribed in 66.4%, and tablets (dragées) in 33.6% of the patients. For 48% of the patients the HMP was prescribed to treat an acute or chronic disease, 25% of the patients received it for prophylaxis, and 27% for both. More than half of the patients (53%) received the HMP as monotherapy. Main treatment indications were UTIs (34.1%) and pyelonephritis (30.0%). The proportion of UTIs was the highest within the youngest age group (51%), while the proportion of different cystitis forms increased in patients older than 2 years. Relevant proportions of different nephritis forms and urolithiasis were only observed in patients aged 12–17 years. Forms of cystitis were more frequent in female than in male patients (15% vs. 1%), while forms of nephritis, urolithiasis, and dysmetabolic nephropathy / crystalluria were more frequent in male patients. At the end of the observational period, 20% of the patients were reported as recovered from their disease, and 65% were reported to show improvements. For 91% of all patients with HMP monotherapy the investigators evaluated the effectiveness of the HMP as ‘good’ or ‘very good’. Nearly all patients (99%) evaluated the tolerability as ‘good‘or ‘very good‘. Five adverse drug reactions were observed. Conclusions The treatment of children aged 1–17 years with the HMP is safe and well tolerated. The study results support the use of the HMP for treatment and prophylaxis of urinary system diseases

Expression of proto-oncogene <it>KIT</it> is up-regulated in subset of human meningiomas

<p>Abstract</p> <p>Background</p> <p><it>KIT</it> is a proto-oncogene involved in diverse neoplastic processes. Aberrant kinase activity of the KIT receptor has been targeted by tyrosine kinase inhibitor (TKI) therapy in different neoplasias. In all the earlier studies, KIT expression was reported to be absent in meningiomas. However, we observed <it>KIT</it> mRNA expression in some meningioma cases. This prompted us to undertake its detailed analyses in meningioma tissues resected during 2008–2009.</p> <p>Methods</p> <p>Tumor tissues and matched peripheral blood samples collected from meningioma patients were used for detailed molecular analyses. KIT expression was ascertained immunohistochemically and validated by immunoblotting. <it>KIT</it> and <it>KITLG</it> transcript levels were discerned by reverse transcription quantitative real-time PCR (RT-qPCR). Similarly, <it>KIT</it> amplification and allele loss were assessed by quantitative real-time (qPCR) and validated by fluorescence <it>in situ</it> hybridization (FISH) on the neoplastic tissues. Possible alterations of the gene at the nucleotide level were analyzed by sequencing.</p> <p>Results</p> <p>Contrary to earlier reports, KIT expression, was detected immunohistochemically in 20.6% meningioma cases (n = 34). Receptor (<it>KIT)</it> and ligand (<it>KITLG)</it> transcripts monitored by RT-qPCR were found to co-express (p = 0.048) in most of the KIT immunopositive tumors. 1/7 KIT positive meningiomas showed allele loss corroborated by reduced FISH signal in the corresponding neoplastic tissue. Sequence analysis of <it>KIT</it> showed M541L substitution in exon 10, in one of the immunopositive cases. However, its biological consequence remains to be uncovered.</p> <p>Conclusions</p> <p>This study clearly demonstrates KIT over-expression in the human meningiomas. The data suggest that up-regulated <it>KIT</it> transcription (p < 0.001), instead of gene amplification (p > 0.05), is a likely mechanism responsible for altered KIT expression. Thus, <it>KIT</it> is a potential candidate for detailed investigation in the context of meningioma pathogenesis.</p

Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation

International audienceBackground: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry.Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0–4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations.Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.</jats:p