Transitions Study of predictors of illness progression in young people with mental ill health: study methodology.

AIM: An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13-24-year-olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post-pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder. METHOD: This paper describes the study methodology, which involves a longitudinal cohort design implemented within four headspace youth mental health services in Australia. Participants are young people aged 12-25 years who have sought help at headspace and consented to complete a comprehensive assessment of clinical state and psychosocial risk factors. A total of 802 young people (66% female) completed baseline assessments. Annual follow-up assessments have commenced. CONCLUSIONS: The results of this study may have implications for the way mental disorders are diagnosed and treated, and progress our understanding of the pathophysiologies of complex mental disorders by identifying genetic or psychosocial markers of illness stage or progression.

A novel mutation in CRYBB2 responsible for inherited coronary cataract.

PURPOSE: To study the molecular pathogenesis of a Chinese family with coronary form of cataract. METHODS: One Chinese three-generation family with inherited coronary cataract phenotype was recruited. Five affected and seven unaffected family members attended our study. Genome-wide linkage analysis was applied to map the disease loci, and two candidate genes from a locus on chromosome 1 and a locus on chromosome 22 were sequenced for mutation identification. Software at the Expasy proteomics server was utilized to predict the mutation effect on proteins. RESULTS: Whole genome linkage analysis indicated some regions on chromosome 1, 10, and 22, with LOD score values greater than 1. Within these loci, the GJA8 and CRYBB2 genes, located in the two loci with the highest LOD score of 1.51 on chromosomes 1 and 22, respectively, were sequenced. A novel mutation c.92C>G in exon 2 of CRYBB2 causing S31W was identified in all five patients. It was not found in 95 unrelated controls. This missense sequence alteration likely enhanced the local solubility. Around the mutation site, a lipocalin signature motif was predicted by ScanProsite. CONCLUSIONS: A novel disease-causing mutation S31W in CRYBB2 was identified in a Chinese cataract family. It is the first reported mutation for coronary cataract. Functional characterization should be carried out to evaluate the biological effects of this mutant.

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study.

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

High-field 1H and 31P NMR studies on the binding of the anticancer agent mitoxantrone to d[CpGpApTpCpG]2.

A high-field 1H and 31P-NMR study of the oligomer d[CpGpApTpCpG]2 was carried out in H2O and water signal suppression was employed in all 1H NMR acquisitions. Particular attention was given to imino proton and 31P assignments. Two dimensional 31P-1H shift correlation contours were particularly useful in 31P assignments and confirming previous 1H assignments. Titrimetric addition of aliquots of the anticancer agent mitoxantrone resulted in selective and progressive chemical shifts with critical changes at stoichiometries of 1:1 and 2:1 drug to DNA ratios. The results indicate ultimate intercalative binding of the drug at both C.G. termini of the oligomer in accord with the previously determined C.G. preference and with non-nearest neighbor intercalation.