Hepatitis C virus (HCV) polymerase activity is essential for HCV replication. Targeted screening of nucleoside analogs identified R1479 (4-azidocytidine) as a specific inhibitor of HCV replication in the HCV subgenomic replicon system (IC 50 ‫؍‬ 1.28 M) with similar potency compared with 2-C-methylcytidine (IC 50 ‫؍‬ 1.13 M). R1479 showed no effect on cell viability or proliferation of HCV replicon or Huh-7 cells at concentrations up to 2 mM. HCV replicon RNA could be fully cleared from replicon cells after prolonged incubation with R1479. The corresponding 5-triphosphate derivative (R1479-TP) is a potent inhibitor of native HCV replicase isolated from replicon cells and of recombinant HCV polymerase (NS5B)-mediated RNA synthesis activity. R1479-TP inhibited RNA synthesis as a CTP-competitive inhibitor with a K i of 40 nM. On an HCV RNA-derived template substrate (complementary internal ribosome entry site), R1479-TP showed similar potency of NS5B inhibition compared with 3-dCTP. R1479-TP was incorporated into nascent RNA by HCV polymerase and reduced further elongation with similar efficiency compared with 3-dCTP under the reaction conditions. The S282T point mutation in the coding sequence of NS5B confers resistance to inhibition by 2-C-MeATP and other 2-methyl-nucleotides. In contrast, the S282T mutation did not confer cross-resistance to R1479. Hepatitis C virus (HCV)2 infection is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma and is currently the leading cause of liver transplantation (1, 2). Viral genome sequence analysis established six HCV genotype classes (HCV genotypes 1-6), with genotypes 1-3 being the most prevalent in the United States, Europe, and Japan. Current treatment options available to HCV-infected persons are limited, and sustained virological response rates are particularly low for HCV genotype 1-infected patients. Only ϳ50% of individuals infected with HCV genotype 1 with serum viral titers of Ͼ2 ϫ 10 6 copies/ml achieved sustained virological response rates when treated with a combination of pegylated interferon-␣ and ribavirin (3, 4). Response rates are even lower in persons with HIV co-infection or cirrhosis and also decrease with age (1, 5-7). Urgently required improvements in anti-HCV therapy will depend on the development of novel therapeutic approaches, especially in difficult to treat populations.HCV is an enveloped (ϩ)-strand RNA virus that enters host cells via receptor-mediated endocytosis and replicates in the host cell cytoplasm. A membrane-associated replicase complex containing HCV genome-encoded nonstructural proteins and HCV genomic RNA in a tight complex is responsible for the formation of viral RNA for packaging into new virus particles during the HCV replication process. The viral NS5B protein contains the HCV polymerase active site within the replicase complex, an RNA-dependent RNA polymerase. The concept of polymerase inhibition to attain antiviral efficacy has been successfully established in other viral infections (human immunodefi...

SUMMARY One hundred and ninety five children aged up to 6 years with burns and scalds (30 non-accidental and 165 accidental) were studied retrospectively. The history, presentation, and other typical injuries assisted the diagnosis of abuse.Scalds accounted for 81% of accidents and 25% of the cases of abuse, and burns for 17% and 44%, respectively. Scalds usually followed spillage from kitchen containers in accidents and forced tap water immersion in cases of abuse. Burns in cases of both accidents and abuse resulted from contact with a wide range of household appliances, including room heaters.Attention is drawn to the back of the hand as an important site in cases of abuse, as well as the legs, buttocks, and feet. It is speculated that the low level of reporting of this form of child abuse reflects failure of diagnosis.

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Aim-To study the outcome over an eight year period of children determined by paediatricians in 1989 as definitely or probably sexually abused. Method-Information was obtained on 140 of 148 children diagnosed in 1989 when aged 7 or less. Sources were hospital medical records and school health records. School health records of a comparison group of 83 children were also examined. Results-A variety of problematic characteristics were found significantly more often in the abused group than the comparison group. These included surname changes (30% v 2%), removal from home (25% v 1%), number of home addresses (2.8 v 1.4), and schools attended (3.4 v 2.2). Other significant findings included further abuse (35% v 0%), adverse behaviours (60% v 16%), educational problems (24% v 5%), chronic health problems (54% v 36%), and involvement of mental health services (32% v 1%).

Armed combat in childhood is a form of child abuse. It may lead to serious consequences, including post‐traumatic stress disorder. The inherent emotional abuse and acts or omissions by caregivers may cause behavioural, cognitive, emotional or mental disorder in the child. Nineteen former child soldiers were interviewed in a rehabilitation centre using a standard questionnaire. Reasons for recruitment included: volunteered (18), hatred of enemy (revenge) (5), virtue of being a freedom fighter (martyrdom) (9), as a means of supporting their family (economic) (3). One child was abducted, 7 joined for fear of the ‘enemy’ abducting them, and in 5 a family member was killed by ‘enemy’ or own group. The children were involved in manual labour (15), guard duty (15), front‐line fighting (7), bomb manufacture (5), setting sea/land mines (5) and radio and communication (2). Fifteen were trained in firearms and 14 in self‐destruction. Twelve children attempted to or did run away and 11 refused to obey orders or argued. This led to various punishments, including kitchen duty, beatings, imprisonment, blackmail or death threats. A majority of the children felt sad and emotionally upset when they remembered their mother and family. Children's involvement in war, whatever the ‘justifications’ may be, should always be considered as forced, as they cannot truly comprehend their action in war. The responsibility must be taken by the adult caregivers. The following definition of the abuse of children in armed conflict is proposed: ‘The involvement of dependent, developmentally immature children and adolescents in armed conflict they do not truly comprehend, to which they are unable to give informed consent, and which adversely affects the child's right to unhindered growth and identity as a child’. Firm international agreement on guidelines for the lower age limit of recruitment of children into armed forces is required. Copyright © 2001 John Wiley & Sons, Ltd.

Left: Contact burns in 2 year old boy with developmental retardation who was abused by his mother. Burns to penis were also present. Right: End of curtain wire heated in fire that was responsiblefor burns

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