Evidence of transient enhancement to cognitive functioning in healthy young adults through environmental enrichment: implications for rehabilitation after brain injury.

We examined preliminarily whether intensive mental activity can transiently enhance higher cognitive functioning in healthy adults. Ten healthy participants performed intensive mental activity for 2 weeks. The intervention entailed daily memorization of multiple prose passages and performance of demanding, speeded mental arithmetic.Neuropsychological testing was conducted before and after the intervention, using alternate forms. (The intervention and neuropsychological tests were different.) Findings in the intervention group were compared to those of a convenience control sample who had performed a near-identical neuropsychological assessment and follow-up in a different study, but who did not perform the intervention. The purpose was to rule out practice effects as the cause of any observed improvement in the intervention group. The intervention group showed improvement on six/eight measures. The non-intervention group showed improvement on only two. Results suggest cognitive capacity can be enhanced in healthy individuals after a period of intensive cognitive stimulation. Implications for rehabilitation are discussed.

Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage.

Anagrelide (ANA) and hydroxycarbamide (HC) are two distinct pharmacological agents used to treat thrombocythaemia associated with myeloproliferative disorders. Although both drugs have been in clinical use for a number of years, comparative studies of their selectivity and mode of action are still lacking. Here, we have evaluated the activities of ANA and HC on the growth and differentiation of human haematopoietic progenitor cells in liquid culture. Both drugs inhibited thrombopoietin-induced megakaryocytopoiesis in a dose-dependent manner, but with strikingly different potencies (IC(50)=26 nM for ANA and 30 muM for HC) and modes of action. Whereas HC inhibited cell proliferation, ANA acted primarily on the differentiation process. At doses that abrogated megakaryocytopoiesis, HC also inhibited the expansion of CD34(+) cells stimulated by stem cell factor, interleukin-3 and Flt-3 ligand and also induced apoptosis. Furthermore, HC inhibited erythroid and myelomonocytic cell growth, induced by erythropoietin or granulocyte-macrophage colony-stimulating factor, respectively. In contrast, ANA showed none of these additional effects. Taken together, these results demonstrate that ANA is a potent and selective inhibitor of megakaryocytopoiesis, having no significant activity against haematopoietic progenitor cell expansion or differentiation into other lineages. In contrast, the anti-megakaryocytopoietic activity of HC cannot be dissociated from its more general cytoreductive and cytotoxic actions.

The isolation and synthesis of novel nematocidal dithiocyanates from an Australian marine sponge, Oceanapia sp.

Bioassay-directed fractionation of the EtOH extract of an Oceanapia sp. collected off the northern Rottnest Shelf, Australia, has yielded three novel dithiocyanates, thiocyanatins A (1), B (2a), and C (2b). The structures were determined by detailed spectroscopic analysis and confirmed by total synthesis. In addition to featuring an unprecedented dithiocyanate functionality, thiocyanatins possess an unusual 1,16-difunctionalized n-hexadecane carbon skeleton and are revealed as a hitherto unknown class of nematocidal agent.

Routine neonatal examination: effectiveness of trainee paediatrician compared with advanced neonatal nurse practitioner.

OBJECTIVE: To compare the effectiveness of routine neonatal examination performed by senior house officers (SHOs) and advanced neonatal nurse practitioners (ANNPs). DESIGN: A prospective study of all infants referred to specialist orthopaedic, ophthalmology, and cardiology clinics. A standardised proforma was used to record details of the professional performing the neonatal check, any abnormalities discovered, source of ultimate referral to the specialist clinic, and specialist findings. RESULTS: 527 eligible infants were recruited. For hip abnormalities, ANNPs displayed greater sensitivity than SHOs (96% v 74%; p < 0.05). Similarly for eye abnormalities, ANNPs were more sensitive (100% v 33%; p < 0.05). There were no significant differences between ANNPs and SHOs in terms of positive predictive values or effectiveness of detecting cardiac abnormalities. There was no difference in underlying incidence of abnormalities between the two hospitals. CONCLUSION: ANNPs are significantly more effective in detecting abnormalities during the neonatal check. This has implications both for future workforce planning and current methods of medical training.

Lorneamides A and B: two new aromatic amides from a southern Australian marine actinomycete.

A marine actinomycete (MST-MA190) isolated from a sample of beach sand collected near Lorne on the southwest coast of Victoria, Australia, has yielded two new aromatic amides, lorneamide A (1) and lorneamide B (2). The lorneamides belong to a novel class of tri-alkyl-substituted benzenes, and their structures were determined by spectroscopic methods.

Geodin A magnesium salt: A novel nematocide from a southern australian marine sponge, geodia

A Geodia species collected from southern Australian waters of the Great Australian Bight has yielded a potent new in vitro nematocidal agent identified as geodin A Mg salt (1), a new macrocyclic polyketide lactam tetramic acid magnesium salt. The structure for 1 was assigned on the basis of detailed spectroscopic analysis.

Individualised bereavement care.

The stories of nine women who have lost a child in the neonatal period were obtained using semi-structured interviews. Interviews were transcribed, 'anonymised' and sorted into categories. Although the data can be grouped in sections according to predominant themes such as 'discontinuation of treatment', 'photographs and memories', 'partners' and 'conflict over treatment', the stories highlight the individual nature of each bereavement experience. Some of the women were satisfied with the individualised care they had received, but there were examples of staff providing care based on assumptions that would be appropriate for most women, but not for the person concerned.

The antianginal agent ranolazine is a weak inhibitor of the respiratory complex I, but with greater potency in broken or uncoupled than in coupled mitochondria.

Ranolazine (RS-43285) has shown antianginal effects in clinical trials and cardiac anti-ischaemic activity in several in vivo and in vitro animal models, but without affecting haemodynamics. Its mechanism is thought to mainly involve a switch in substrate utilisation from fatty acids to glucose to, thus, improve efficiency of O2 use; however, its precise molecular target(s) are unknown. In studies to investigate its action further, using isolated rat heart mitochondria, ranolazine was found to weakly inhibit (pIC50 values > 300 microM) respiration by coupled mitochondria provided with NAD(+)-linked substrates but not with succinate. With broken mitochondrial membranes or submitochondrial particles, ranolazine inhibited NADH but not succinate oxidation and with pIC50 values in the lower range of 3-50 microM. Studies with different electron acceptors and respiratory inhibitors indicated that it inhibits respiratory Complex I at a site between ferricyanide and menadione and ubiquinone-1 reduction (i.e. at a similar locus to rotenone). However, unlike rotenone, ranolazine was an uncompetitive inhibitor with respect to ubiquinone-1. Ranolazine inhibition of Complex I was reversible and occurred also with mitochondria from pig, guinea pig, and human heart, and rat liver. Further studies using rat heart mitochondria in different energisation states (i.e. broken, uncoupled, or coupled) showed a 50-100-fold shift to greater potency of ranolazine in the broken compared to the coupled; with the uncoupled it was about 2-fold less potent than the broken. These shifts in potency were not found with rotenone or amytal. Studies with radiolabelled ranolazine showed that it bound to mitochondrial membranes with greater affinity in the broken compared to the coupled or uncoupled conditions. Rotenone displaced radiolabelled ranolazine from its binding site. This property of ranolazine may play some role in its anti-ischaemic activity.