Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.     

Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study

The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer’s disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N?=?23) versus no e4 allele (non-carriers, N?=?41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p?=?.038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.     

Graduate attributes in the disciplines of Medicine, Dentistry and Veterinary Medicine: a survey of expert opinions

Background  

This study was completed as part of a project for the Quality Assurance Agency on the enhancement theme of 'Research teaching linkages: enhancing graduate attributes' in the disciplines of Medicine, Dentistry and Veterinary Medicine. The aims of this investigation were to elucidate a list of desirable research related graduate attributes for the disciplines of Medicine, Dentistry and Veterinary Medicine and provide evidence as to how they could be covered within such curricula.     

Prevalence of psychiatric disorders in New Zealand prisons: a national study

OBJECTIVE: The paper describes the methodologies and results obtained on a large cohort of prison inmates in New Zealand who were screened for psychiatric disorder. METHOD: All women and remanded male inmates in New Zealand prisons, and a randomly selected cohort of 18% of sentenced male inmates were interviewed. Interviewers used the Composite International Diagnostic Interview - Automated to establish DSM-IV diagnoses, and the Personality Disorders Questionnaire to identify personality disorder. All prisons in New Zealand were visited. RESULTS: The results indicate markedly elevated prevalence rates for major mental disorder in the prison population when compared with community samples. This is especially the case for substance misuse, psychotic disorders, major depression, bipolar disorder, obsessive- compulsive disorder and posttraumatic stress disorder. Of particular concern is not only the increased prevalence rates for schizophrenia and related disorders but also the high level of comorbidity with substance misuse disorders demonstrated by this group. While 80.8% of inmates diagnosed with bipolar disorder were receiving psychiatric treatment in the prison, only 46.4% of depressed inmates and 37% of those suffering from psychosis were receiving treatment. Maori inmates were grossly overrepresented in the remand, female and male sentenced inmate population compared with the general population. CONCLUSIONS: A significant increase in provision of mental health services is required to cope with the high number of mentally ill inmates. The level of need demonstrated by this study requires a level of service provision that is quite beyond the capacity of current forensic psychiatry services, Department of Corrections Psychological Services or the prison nursing and medical officers. The elevated rates of common mental disorders argues for the use of improved psychiatric screening instruments, improved assessment and treatment capacities in the prison and an increased number of forensic psychiatric inpatient facilities to care for those psychotic inmates who are too unwell to be treated in the prison.