Molecular psychiatry of zebrafish.

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research.

The psychological wellbeing of patients following excision of a pilonidal sinus.

OBJECTIVE: To explore the effects of a pilonidal sinus wound on patients' psychological wellbeing. METHOD: An interpretive descriptive approach, using the Model of Living conceptual framework, guided data collection and analysis. The Model of Living was chosen to elicit information on how a pilonidal sinus wound affected activities of living. Participants were recruited from a database of a community nursing service, using purposive sampling, until data saturation was evident. Semi-structured interviews were used to collect the data. Data were examined for frequent patterns, which were organised into themes. RESULTS: Seven males and four females with ages ranging 17-39 years were selected through purposive sampling. Five participants reported that their wound affected their psychological wellbeing. Three themes and eight sub themes were identified from the data: adaption, perception and control. Depression and stress were associated with pain, physical inactivity, body weight changes and delayed wound healing. CONCLUSION: A pilonidal sinus wound can affect the psychological wellbeing of patients through pain,physical inactivity, changed body weight and delayed wound healing. Pre-existing conditions could also be exacerbated by the wound.

Mantel-Haenszel analysis of Oxford data. II. Independent effects of fetal irradiation subfactors.

A Mantel-Haenszel analysis of fetal irradiation subfactors indicated that most of the "extra" X-rayed cases in the Oxford Survey of Childhood Cancers were radiation induced. First trimester exposures were rare but probably ten times more dangerous than later exposures. Ratios of observed: expected numbers of cancer deaths were lower for children with abnormal X-rays than for other X-rayed children, and lower for recent than remote exposures. The first of these differences was probably due to several antenatal conditions having positive associations with obstetric radiography and several causes of early (noncancer) deaths; the second one was probably due to a progressive lowering of film doses between 1940 and the present time. A rare cause of fetal irradiation (hydramnios), whose associations with congenital defects are well documented, led to the discovery that two faults in the International Classification of Diseases and Causes of Death have contributed to mistaken ideas about the etiology of childhood cancers: Neoplasms were not listed among the official causes of stillbirths, and cystic tumors of the kidneys and lungs of infants were not listed as neoplasms.

Mantel-Haenszel analysis of Oxford data. I. Independent effects of several birth factors including fetal irradiation.

Data from the Oxford Survey of Childhood Cancers were subjected to the Mantel-Haenszel procedures to recognize independent effects of associated factors in retrospective data. Our results showed that several birth factors, including fetal irradiation, social class, maternal age, and sibship position, exerted separate effects on childhood cancers in general, and reticuloendothelial system neoplasms in particular.

Mitochondrial DNA mutations in an outbreak of optic neuropathy in Cuba.

Since October 1991, nearly 51,000 Cubans have been afflicted in an outbreak of optic and peripheral neuropathies. To begin an investigation of the possible role of mitochondrial DNA (mtDNA) mutations in the outbreak, we studied mtDNA from 14 affected and two unaffected Cubans for the 12 mutations associated with Leber's hereditary optic neuropathy. Eleven probands (12 patients) had optic neuropathy and two had peripheral neuropathy only. We also studied two unaffected relatives of one proband. We identified two mtDNA mutations, at nucleotides 11778 and 3460, in two of the 11 probands with optic neuropathy. Although this data set is too small to reach statistically valid conclusions, it does suggest that mtDNA mutations might be contributing to the outbreak of optic neuropathy in Cuba.

A 12-month comparative trial of auranofin and D-penicillamine in rheumatoid arthritis.

The oral gold salt auranofin, 6 mg per day, was compared with oral d-penicillamine, 500 mg per day, in a single-blind trial in 40 patients suffering with definite or classic rheumatoid arthritis. The patients were randomly allocated into the two therapeutic regimens (19 patients auranofin; 21 patients d-penicillamine) and monitored at a minimum of four-week intervals during the first year of treatment. Significant diminution in rheumatoid disease activity, as assessed by numerous clinical and laboratory parameters, was observed in both the auranofin- and penicillamine-treated groups. No significant differences existed for these parameters between the two groups, either initially or at the end of the trial period. Ten patients were lost from the trial over the 52-week period. Three subjects were withdrawn from the auranofin-treated group (increasing severity of rheumatoid arthritis at four weeks; severe diarrhea at four weeks; probable drug-related erosive gastritis at 40 weeks). Seven subjects were permanently withdrawn from the penicillamine-treated group (four, skin rashes four to eight weeks; one, heavy proteinuria at 24 weeks; one, therapeutic failure at 32 weeks; one, compliance failure at eight weeks), and treatment was temporarily withheld in three further patients because of thrombocytopenia (two) and proteinuria (one). We conclude that both drugs are effective in rheumatoid arthritis and that the lesser toxicity with auranofin will make it a valuable addition to our therapeutic armamentarium.

A-bomb survivors: factors that may lead to a re-assessment of the radiation hazard.

BACKGROUND: The study cohort of the survivors of the A-bombs in Japan, used as the basis of the internationally accepted estimates of cancer radiation risk, was collected more than 5 years after the bombing and did not include those who died of bomb-related injuries before that date. This paper tests whether the people who survived, in spite of bomb-related injuries, are homogeneous in respect of variation of cancer risk with age with survivors without such injuries. METHODS: Appropriate statistical models are derived and fitted to survivor data by maximum likelihood and the resultant statistics used to test the homogeneity assumption. RESULTS: Significant differences were found between those with no injuries and those with multiple injuries and shown to be largely due to exposures before 10 or after 55 years of age having exceptionally high risks of late effects of radiation for survivors showing early effects, i.e. bomb-related injuries. CONCLUSIONS: Certain accepted dogmas about the biology of radiation risks in humans, such as 'cancer is the only late effect of radiation' and 'leukaemia is uniquely radiogenic amongst cancers', may be significantly in error. These are discussed.