Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations

The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow‐wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty‐eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night‐time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired‐associate word list task, while procedural memory was tested using the mirror‐tracing task. All participants underwent high‐resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow‐wave sleep as previously conceptualized.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy

Mutations in the sodium channel genes SCN1A and SCN2A have been identified in monogenic childhood epilepsies, but SCN3A has not previously been investigated as a candidate gene for epilepsy. We screened a consecutive cohort of 18 children with cryptogenic partial epilepsy that was classified as pharmacoresistant because of nonresponse to carbamazepine or oxcarbazepine, antiepileptic drugs that bind sodium channels. The novel coding variant SCN3A-K354Q was identified in one patient and was not present in 295 neurological normal controls. Twelve novel SNPs were also detected. K354Q substitutes glutamine for an evolutionarily conserved lysine residue in the pore domain of SCN3A. Functional analysis of this mutation in the backbone of the closely related gene SCN5A demonstrated an increase in persistent current that is similar in magnitude to epileptogenic mutations of SCN1A and SCN2A. This observation of a potentially pathogenic mutation of SCN3A (Nav1.3) indicates that this gene should be further evaluated for its contribution to childhood epilepsy.     

Disclosure,confidentiality, and families: experiences and attitudes of those with genetic versus nongenetic medical conditions

Despite policy attention to medical privacy and patient confidentiality, little empirical work exists documenting and comparing experiences of persons with genetic versus nongenetic medical conditions concerning persons' disclosure to others as well as their views about appropriate confidentiality to and within families. The goal of this cross-sectional interview study with nearly 600 participants was to document and compare the experiences, attitudes, and beliefs of persons with strictly genetic conditions to those of persons with or at risk for other serious medical conditions in terms of the degree to which they have disclosed to others that they have the condition and their views about how others ought to maintain the confidentiality of that information. While almost all participants reported that family members knew about their condition, results suggest participants want to control that disclosure themselves and do not want doctors to disclose information to family members without their knowledge. Similarly, participants do not think family members should be able to get information about them without their knowledge but feel overwhelmingly that it is a person's responsibility to disclose information about hereditary conditions to other family members. Ambivalence about confidentiality was evident: while most participants did not mind doctors sharing information with other doctors when it was for their benefit, the majority also felt that doctors should be punished for releasing information without their permission. The views and experiences reported here generally did not differ by whether participants had genetic versus nongenetic conditions, suggesting that the extensive policy focus on genetic information may be unwarranted.     

Neuronal activity in macaque supplementary eye field during planning of saccades in response to pattern and spatial cues

The aim of this study was to determine whether neuronal activity in the macaque supplementary eye field (SEF) is influenced by the rule used for saccadic target selection. Two monkeys were trained to perform a variant of the memory-guided saccade task in which any of four visible dots (rightward, upward, leftward, and downward) could be the target. On each trial, the cue identifying the target was either a spot flashed in superimposition on the target (spatial condition) or a foveally presented digitized image associated with the target (pattern condition). Trials conforming to the two conditions were interleaved randomly. On recording from 439 SEF neurons, we found that two aspects of neuronal activity were influenced by the nature of the cue. 1) Activity reflecting the direction of the impending response developed more rapidly following spatial than following pattern cues. 2) Activity throughout the delay period tended to be higher following pattern than following spatial cues. We consider these findings in relation to the possible involvement of the SEF in processes underlying attention, arousal, response-selection, and motor preparation.     

Health-related quality of life among people with HIV disease: Results from the Multicenter AIDS Cohort Study

To examine the effect of HIV status, symptomatology and CD4+ lymphocyte level on health-related quality of life, the Medical Outcomes Study Short-Form Health Survey (SF-36) was administered to 2,295 gay men enrolled in the Multicenter AIDS Cohort Study (MACS) in 1994. Distinct physical and mental health factors of the SF-36 were found. Seropositive asymptomatic individuals and seropositive individuals with CD4+ lymphocytes 500/mm³ scored as well as seronegative participants on all of the mental health domain scales, but lower on the general health perceptions and physical health composite score. Seropositive individuals with at least one symptom or with CD4+ lymphocytes below 200/mm³ scored significantly lower on all of the SF-36 scales and summary scores than seronegative controls. The SF-36 was found to exhibit similar mental and physical health factors for an adult gay male population to that previously seen in general population samples and in patient groups with other diseases. In conclusion, HIV-positive men who are asymptomatic or have CD4+ lymphocytes above 500/mm³ have similar perceived mental health but worse perceived physical health than seronegative men. HIV-positive men who are symptomatic or have CD4+ lymphocytes below 200/mm³ have worse perceived mental and physical health than seronegative men.