RESUMO
Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains (n = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the VP1 gene from a larger CVA4 collection (n = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, VP1 was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of VP1 was estimated to be 5.12 × 10-3 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in VP1 gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China.
RESUMO
BACKGROUND: High fluoride exposure can result in dental fluorosis. Fluoride and iodine are coexistent in the drinking water of areas in China and may affect the prevalence of dental fluorosis and osteogenesis. The aim of this study was to investigate the relationship between serum calciotropic hormone level, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water. METHODS: A pilot study was conducted in three villages located in the Kaifeng and Tongxu counties of Henan Province, China in 2006. Children aged 8 to 12 years, born and raised in the three villages were recruited. The fluoride levels in the samples of urine from these children were detected by fluoride ion selective electrode. Calcitonin and osteocalcin levels in the serum, and serum calcium were measured by radioimmunassay and flame atomic absorption spectrometry, respectively. RESULTS: Fluoride levels in urine were significantly lower in children from control area (CA) as compared with those from the high fluoride & iodine areas (HFIA) and the high fluoride area (HFA) (P < 0.05 respectively), and no statistically significant difference was found between the children from HFIA and HFA. Additionally, calcitonin levels in the serum were significantly lower in children from CA and HFA as compared with that from HFIA (P < 0.05 respectively), and osteocalcin levels in the serum was lower in children from CA than those from HFIA (P < 0.05). No statistically significant difference in serum osteocalcin concentrations was found between children from HFA and HFIA. CONCLUSION: This study provides an evidence that iodine exposure may modify the serum calciotropic hormone levels related to fluorine exposure.