Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases.

Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past twenty years that the molecular events that precipitate disease have begun to be understood. Protein aggregation is a common feature of many neurodegenerative diseases, and it is assumed that the aggregation process plays a central role in pathogenesis. In this process, one molecule (monomer) of a soluble protein interacts with other monomers of the same protein to form dimers, oligomers, and polymers. Conformation changes in three-dimensional structure of the protein, especially the formation of beta-strands, often accompany the process. Eventually, as the size of the aggregates increases, they may precipitate as insoluble amyloid fibrils, in which the structure is stabilized by the beta-strands interacting within a beta-sheet. In this review, we discuss this theme as it relates to the two most common neurodegenerative conditions-Alzheimer's and Parkinson's diseases.

Impact of cough across different chronic respiratory diseases: comparison of two cough-specific health-related quality of life questionnaires

Background: Cough is a prominent symptom across a range of common chronic respiratory diseases and impacts considerably on patient health status.

Methods: We undertook a cross-sectional comparison of scores from two cough-specific health-related quality of life (HRQoL) questionnaires, the Leicester Cough Questionnaire (LCQ), and the Cough Quality of Life Questionnaire (CQLQ), together with a generic HRQoL measure, the EuroQol. Questionnaires were administered to and spirometry performed on 147 outpatients with chronic cough (n = 83), COPD (n = 18), asthma (n = 20), and bronchiectasis (n = 26).

Results: There was no significant difference in the LCQ and CQLQ total scores between groups (p = 0.24 and p = 0.26, respectively). Exploratory analyses of questionnaire subdomains revealed differences in psychosocial issues and functional impairment between the four groups (p = 0.01 and p = 0.05, respectively). CQLQ scores indicated that chronic coughers have more psychosocial issues than patients with bronchiectasis (p = 0.03) but less functional impairment than COPD patients (p = 0.04). There was a significant difference in generic health status across the four disease groups (p = 0.04), with poorest health status in COPD patients. A significant inverse correlation was observed between CQLQ and LCQ in each disease group (chronic cough r = - 0.56, p < 0.001; COPD r = - 0.49, p = 0.04; asthma r = - 0.94, p < 0.001; and bronchiectasis r = - 0.88, p < 0.001). There was no correlation between cough questionnaire scores and FEV1 in any group, although a significant correlation between EuroQol visual analog scale component and FEV1 (r = 0.639, p = 0.004) was observed in COPD patients.

Conclusion: Cough adversely affects health status across a range of common respiratory diseases. The LCQ and CQLQ can each provide important additional information concerning the impact of cough.

It's Better to Stick to your own Kind: Teenagers' Views on Cross-community marriages in Northern Ireland

This article presents the attitudes of 80 teenagers-growing up in one of the most contested localities in Northern Ireland-to cross-community marriages, i.e. those between Catholics and Protestants. Research suggests that adults in interface areas continue to exhibit ethno-sectarian prejudices despite wider political developments such as the Good Friday Agreement. The teenagers perceived that their families would be largely unsupportive of cross-community unions but felt that their own views were much less prejudiced than those of their parents. However, while the majority of teenagers had no objections in principle to marrying outside their religious group, they outlined a number of practical difficulties which couples from cross-community unions would face. These included deciding where to live, in which religion, if any, to bring children up and where to send children to school. Most of the teenagers suggested that these potential problems would work against them marrying outside their own religious group. These practical dilemmas provide a more nuanced set of reasons for marrying within one's own community than dilemmas based on traditional prejudices and stereotypes and suggest that teenagers living in sectarian enclaves are more receptive to cross-community marriages than their parents.

Social and Subcultural Capital among teenagers in Northern Ireland

This article makes a case for the inclusion of subcultural capital as an indictor of social capital networks in the lives of teenagers. It does so by critiquing approaches that assume that adult measures of social capital can be nonproblematically extended to account for stocks of social capital held by younger generations. To illustrate the fallacy of this approach, this article draws on data from the 2003 Northern Ireland Young Life and Times Survey (NIYLTS) and the indicators used to explore the relevance of social capital in the lives of teenagers. By ignoring concepts such as subcultural capital, surveys such as the NILYTS provide partial frameworks for understanding the complexities of young people's links to social capital networks and their inclusive and exclusive effects.

Teenagers in adult psychiatric inpatient care in Northern Ireland

Objectives: To investigate the nature and pattern of teenage admissions (13-18yrs) to the 14 adult psychiatric units in Northern Ireland (NI) between 1989 and 1995.

Molecular diagnosis for heterogeneous genetic diseases with high-throughput DNA sequencing applied to retinitis pigmentosa

BACKGROUND:
The genetic heterogeneity of many Mendelian disorders, such as retinitis pigmentosa which results from mutations in over 40 genes, is a major obstacle to obtaining a molecular diagnosis in clinical practice. Targeted high-throughput DNA sequencing offers a potential solution and was used to develop a molecular diagnostic screen for patients with retinitis pigmentosa.
METHODS:
A custom sequence capture array was designed to target the coding regions of all known retinitis pigmentosa genes and used to enrich these sequences from DNA samples of five patients. Enriched DNA was subjected to high-throughput sequencing singly or in pools, and sequence variants were identified by alignment of up to 10 million reads per sample to the normal reference sequence. Potential pathogenicity was assessed by functional predictions and frequency in controls.
RESULTS AND CONCLUSIONS:
Known homozygous PDE6B and compound heterozygous CRB1 mutations were detected in two patients. A novel homozygous missense mutation (c.2957A?T; p.N986I) in the cyclic nucleotide gated channel ß1 (CNGB1) gene predicted to have a deleterious effect and absent in 720 control chromosomes was detected in one case in which conventional genetic screening had failed to detect mutations. The detection of known and novel retinitis pigmentosa mutations in this study establishes high-throughput DNA sequencing with DNA pooling as an effective diagnostic tool for heterogeneous genetic diseases.