First-episode psychosis: factors associated with delayed access to care in a rural Egyptian setting.

Over the past few decades there has been a growing interest in first-episode psychosis (FEP), help-seeking behaviour and pathways to care. Treating psychotic disorders in their earliest stages has become a key focus for research and clinical care (Yung & McGorry, 2007). FEP studies show that the average time between onset of symptoms and first effective treatment is often 1 year or more (McGlashan, 1987). This long duration of untreated psychosis (DUP) is undesirable. Early treatment helps minimise the risk of the serious consequences of untreated psychosis, in terms of changes in mental state and behaviour (Larsen et al, 1998; Wyatt et al, 1998) and can reduce suffering (Ho et al, 2003). Some early results suggested that an 'early intervention in psychosis' (EIP) service is more cost-effective than generic services (Mihalopoulos et al, 1999).

Efficient repair of bulky anti-BPDE DNA adducts from non-transcribed DNA strand requires functional p53 but not p21(waf1/cip1) and pRb.

Wild-type p53 protein is known to regulate the global genomic repair (GGR), removing bulky chemical DNA adducts as well as cyclobutane pyrimidine dimers from the genome overall and from non-transcribed strands (NTS) in DNA. To investigate the role of cellular factor(s) relevant to p53 regulated DNA repair processes, we examined the repair kinetics of chemical carcinogen, anti-benzo[a]pyrene-diol epoxide (anti-BPDE), induced bulky DNA adducts in normal human mammary epithelial cells (HMECs) and HMEC transformed by human papillomavirus (HPV)-16E6 or -16E7 oncoproteins, which, respectively targets p53 or pRb proteins for degradation. The results show that the removal of anti-BPDE DNA adducts from the genome overall and NTS by GGR was significantly reduced in HPV-16E6 protein expressing cells as compared to that in normal and HPV-16E7 protein expressing cells, indicating the role of p53 and not pRb in nucleotide excision repair (NER). We further determined the potential effects of the p53-regulated p21(waf1/cip1) gene product in NER in human colon carcinoma, HCT116 cells expressing wild-type p53 but different p21(waf1/cip1) genotypes (p21+/+, p21+/-, p21-/-). The results donot show a discernible difference in the removal of anti-BPDE DNA adducts from the genome overall and the transcribed strand (TS) and NTS irrespective of the presence or absence of p21(waf1/cip1) expression. Based on these results, we suggest that: (i) the wild-type p53 function but not p21(waf1/cip1) expression is necessary for GGR of chemical induced bulky DNA adducts; (ii) the Rb gene product does not play a significant role in NER; and (iii) the modulation of NER by p53 may be independent of its function in the regulation of cell cycle arrest upon chemically induced DNA damage.