Indeterminate Sentences for the Severely Personality Disordered

In line with recent incapacitative efforts aimed at dealing with dangerous people in the community, the Government has proposed a new indeterminate sentence to deal with the current gap in the law which exists in relation to dangerous individuals with untreatable severe personality disorders. However, these new measures have serious civil liberty implications and are largely unworkable in practice. It is suggested that rather than introducing these new powers it would be better to consider amending deficiencies which exist in the criminal justice and mental health systems in respect of the management of violent and sexual offenders.

Inhibitors of alpha-synuclein oligomerization and toxicity: a future therapeutic strategy for Parkinson's disease and related disorders.

An abundance of genetic, histopathological, and biochemical evidence has implicated the neuronal protein, alpha-synuclein (alpha-syn) as a key player in the development of several neurodegenerative diseases, the so-called synucleinopathies, of which Parkinson's disease (PD) is the most prevalent. Development of disease appears to be linked to events that increase the intracellular concentration of alpha-syn or cause its chemical modification, either of which can accelerate the rate at which it forms aggregates. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or altered forms of alpha-syn, such as truncations, missense mutations, or chemical modifications by oxidative reactions. Aggregated forms of the protein, especially newly formed soluble aggregates, are toxic to cells, so that one therapeutic strategy would be to reduce the rate at which such oligomerization occurs. We have therefore designed several peptides and also identified small molecules that can inhibit alpha-syn oligomerization and toxicity in vitro. These compounds could serve as lead compounds for the design of new drugs for the treatment of PD and related disorders in the future.

Personality analysis of patients complaining of sialorrhoea

BACKGROUND: Sialorrhoea, the symptom of apparent excessive secretion of saliva is a relatively uncommon complaint. Some authors consider that in the absence of clinical findings, then these patients have a psychiatric disorder masquerading as a physical illness. However, there is little evidence in the literature to support this conclusion and a detailed psychological assessment of this population has not previously been reported. METHODS: In total, 18 patients and 18 age- and sex-matched controls were studied. All had a history of a complaint of excess salivation in the absence of any oral mucosal or systemic abnormality. All patients completed an Eysenck Personality Questionnaire. RESULTS: There were no differences in the extroversion of psychoticism scores between the study and control group. However, the result showed significant increases in the neuroticism and Lie Scale score in the patient group. CONCLUSIONS: The overall results of this study indicate that the complaint of sialorrhoea in otherwise healthy individuals does not have an organic basis and suggest that sialorrhoea is associated with high levels of neuroticism and a tendency to dissimulate. © Blackwell Munksgaard 2006. All rights reserved.

A strategy for designing inhibitors of alpha-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders.

Convergent biochemical and genetic evidence suggests that the formation of alpha-synuclein (alpha-syn) protein deposits is an important and, probably, seminal step in the development of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). It has been reported that transgenic animals overexpressing human alpha-syn develop lesions similar to those found in the brain in PD, together with a progressive loss of dopaminergic cells and associated abnormalities of motor function. Inhibiting and/or reversing alpha-syn self-aggregation could, therefore, provide a novel approach to treating the underlying cause of these diseases. We synthesized a library of overlapping 7-mer peptides spanning the entire alpha-syn sequence, and identified amino acid residues 64-100 of alpha-syn as the binding region responsible for its self-association. Modified short peptides containing alpha-syn amino acid sequences from part of this binding region (residues 69-72), named alpha-syn inhibitors (ASI), were found to interact with full-length alpha-syn and block its assembly into both early oligomers and mature amyloid-like fibrils. We also developed a cell-permeable inhibitor of alpha-syn aggregation (ASID), using the polyarginine peptide delivery system. This ASID peptide was able to inhibit the DNA damage induced by Fe(II) in neuronal cells transfected with alpha-syn(A53T), a familial PD-associated mutation. ASI peptides without this delivery system did not reverse levels of Fe(II)-induced DNA damage. Furthermore, the ASID peptide increased (P

The Apperceptive Personality Test located in personality space.

The Apperceptive Personality Test is a projective test that claims to show good psychometric properties but which has not been related to the main, Eysenckian, personality traits. This study investigated the overlap between these two tests using a sample of students. Correlational and regression analyses showed a modest degree of overlap between Extraversion, Neuroticism and some of the scales from the Apperceptive Personality Test.

Molecular dynamics studies of trinucleotide repeat DNA involved in neurodegenerative disorders.

Expansion of trinucleotide repeat DNA of the classes CAG�·CTG, CGG�·CCG and GAA�·TTC are found to be associated with several neurodegenerative disorders. Different mechanisms have been attributed to the expansion of triplets, mainly involving the formation of alternate secondary structures by such repeats. This paper reports the molecular dynamics simulation of triplet repeat DNA sequences to study the basic structural features of DNA that are responsible for the formation of structures such as hairpins and slip-strand DNA leading to expansion. All the triplet repeat sequences studied were found to be more flexible compared to the control sequence unassociated with disease. Moreover, flexibility was found to be in the order CAG�·CTG > CGG�·CCG = GAA�·TTC, the highly flexible CAG�·CTG repeat being the most common cause of neurodegenerative disorders. In another simulation, a single G�·C to T�·A mutation at the 9th position of the CAG�·CTG repeat exhibited a reduction in bending compared to the pure 15-mer CAGâ�¢CTG repeat. EPM1 dodecamer repeat associated with the pathogenesis of progressive myoclonus epilepsy was also simulated and showed flexible nature suggesting a similar expansion mechanism.