Human hippocampus and viewpoint dependence in spatial memory

Virtual reality was used to sequentially present objects within a town square and to test recognition of object locations from the same viewpoint as presentation, or from a shifted viewpoint. A developmental amnesic case with focal bilateral hippocampal pathology showed a massive additional impairment when tested from the shifted viewpoint compared with a mild, list length-dependent, impairment when tested from the same viewpoint. While the same-view condition could be solved by visual pattern matching, the shifted-view condition requires a viewpoint independent representation or an equivalent mechanism for translating or rotating viewpoints in memory. The latter mechanism was indicated by control subjects' response latencies in the shifted-view condition, although the amnesic case is not impaired in tests of mental rotation of single objects. These results show that the human hippocampus supports viewpoint independence in spatial memory, and suggest that it does so by providing a mechanism for viewpoint manipulation in memory. In addition, they suggest an extremely sensitive test for human hippocampal damage, and hint at the nature of the hippocampal role in episodic recollection.     

A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface

Presenilin 1 (PS1) and presenilin 2 play a critical role in the gamma-secretase processing of amyloid precursor protein (APP) and Notch1. Here, we investigate maturation and intracellular trafficking of APP and other membrane proteins in cells expressing an experimental PS1 deletion mutant (deltaM1,2). Stable expression of deltaM1,2 impairs gamma-secretase processing of Notch1 and delays Abeta secretion. Kinetic studies show enhanced O-glycosylation and sialylation of holo-APP and marked accumulation of APP COOH-terminal fragments (CTFs). Surface biotinylation, live staining, and trafficking studies show increased surface accumulation of holo-APP and CTFs in deltaM1,2 cells resulting from enhanced surface delivery of newly synthesized APP. Expression of a loss-of-function PS1 mutant (D385A) or incubation of cells with gamma-secretase inhibitors also increases surface levels of holo-APP and CTFs. In contrast to APP, glycosylation and surface accumulation of another type I membrane protein, nicastrin, are markedly reduced in deltaM1,2 cells. Finally, expression of deltaM1,2 results in the increased assembly and surface expression of nicotinic acetylcholine receptors, illustrating that PS1's influence on protein trafficking extends beyond APP and other type I membrane protein substrates of gamma-secretase. Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins.     

Direct B-mode NASCET-style stenosis measurement and Doppler ultrasound as parameters for assessment of internal carotid artery stenosis

Doppler ultrasound grading of internal carotid artery (ICA) stenosis using the two parameters of spectral analysis and internal carotid to common carotid artery peak systolic velocity (ICA/CCA PSV) ratio is well established. The improvements in B-Mode ultrasound image quality now make direct ultrasound NASCET-style stenosis measurement possible. We demonstrate that longitudinal B-mode imaging can produce accurate North American Symptomatic Carotid Endarterectomy Trial (NASCET) style measurements which have good correlation with angiographic images. Ultrasound B-mode stenosis measurement provides a third parameter which can be used in conjunction with the two Doppler parameters for the assessment of ICA stenosis. Taking the highest grade of stenosis of the three parameters produces a sensitivity of 100% for the detection of greater than 50% and greater than 80% stenosis with specificity of 66 and 90%, respectively. The performance of satisfactory B-mode imaging against digital subtraction angiography (DSA) was very encouraging. When the B-mode stenosis measurement showed a normal ICA, the positive predictive value (PPV) of the DSA being normal was 94%. When the B-mode stenosis measurement was 35% or less, the PPV of the DSA stenosis being 35% or less was 93%. These excellent results support the use of good quality B-Mode NASCET style stenosis measurement as the initial ultrasound measurement, with Doppler ultrasound only being performed when the B-mode stenosis measurement is greater than 35% or if the B-mode image is unsatisfactory. This approach would save considerable time enabling better utilization of ultrasound resources.     

Magnetic resonance imaging of Trilucent TM breast implants

AIM: To demonstrate the magnetic resonance imaging (MRI) appearances of intact and ruptured Trilucent TM implants with imaging and surgical correlation. The appearances of the implant transponder artefact are also described MATERIALS AND METHODS: A retrospective review of the MRI findings in 34 patients with bilateral subpectoral Trilucent TM breast implants (Lipomatrix, Inc./Collagen Aesthetics International Inc., Neuchatel, Switzerland) was performed. Patients under implant surveillance and those with suspected implant rupture formed the study group. Imaging findings were correlated with surgical appearances. RESULTS: Surgical correlation was available in 53% of patients. Fifty per cent (18/36) of implants were intact at surgery, 50% (18/36) of implants were ruptured. Of the 18 ruptured implants, 17 were intracapsular ruptures and one an extracapsular rupture. The sensitivity of MRI for detection of intracapsular rupture in Trilucent TM breast implants was 82% specificity 76%, positive predictive value 78%, negative predictive value 81% and accuracy 79% in this study group. No case of implant rupture was obscured by the transponder artefact. Four implants were found to have 'pseudocapsules' at surgery (5.9%), the implants were intact with fluid present between the implant and capsule. Only one pseudocapsule was demonstrated on MRI. CONCLUSION: Magnetic resonance imaging is currently the most accurate technique for diagnosis of implant rupture in Trilucent TM breast implants. Transponder artefact does not appear to interfere with the assessment of implant rupture.     

Estimating risk and rate levels,ratios and differences in case-control studies

Classic (or 'cumulative') case-control sampling designs do not admit inferences about quantities of interest other than risk ratios, and then only by making the rare events assumption. Probabilities, risk differences and other quantities cannot be computed without knowledge of the population incidence fraction. Similarly, density (or 'risk set') case-control sampling designs do not allow inferences about quantities other than the rate ratio. Rates, rate differences, cumulative rates, risks, and other quantities cannot be estimated unless auxiliary information about the underlying cohort such as the number of controls in each full risk set is available. Most scholars who have considered the issue recommend reporting more than just risk and rate ratios, but auxiliary population information needed to do this is not usually available. We address this problem by developing methods that allow valid inferences about all relevant quantities of interest from either type of case-control study when completely ignorant of or only partially knowledgeable about relevant auxiliary population information.     

Gradients in risk for youth injury associated with multiple-risk behaviours: a study of 11,329 Canadian adolescents

This study used the Canadian version of the World Health Organization-Health Behaviour in School-Aged Children (WHO-HBSC) Survey to examine the role of multiple risk behaviours and other social factors in the etiology of medically attended youth injury. 11,329 Canadians aged 11-15 years completed the 1997-1998 WHO-HBSC, of which 4152 (36.7%) reported at least one medically attended injury. Multiple logistic regression analyses failed to identify an expected association between lower socio-economic status and risk for injury. Strong gradients in risk for injury were observed according to the numbers of multiple risk behaviours reported. Youth reporting the largest number (7) of risk behaviours experienced injury rates that were 4.11 times (95% CI: 3.04-5.55) higher than those reporting no high risk behaviours (adjusted odds ratios for 0-7 reported behaviours: 1.00, 1.13, 1.49, 1.79, 2.28, 2.54, 2.62, 4.11; p(trend) < 0.001). Similar gradients in risk were observed within subgroups of young people defined by grade, sex, and socio-economic level, and within restricted analyses of various injury types (recreational, sports, home, school injuries). The gradients were especially pronounced for severe injury types and among those reporting multiple injuries. The analyses suggest that multiple risk behaviours may play an important role in the social etiology of youth injury, but these same analyses provide little evidence for a socio-economic risk gradient. The findings in turn have implications for preventive interventions.     

The doctor as God's mechanic? Beliefs in the Southeastern United States

Spiritual practice and beliefs related to healing are described using data from a telephone survey. Questions in the survey address the practice of prayer and spiritual beliefs related to healing. Questions explore belief in miracles, that God acts through religious healers, the importance of God's will in healing, and that God acts through physicians. Questions also ask whether people discuss spiritual concerns with their physician and whether they would want to if seriously ill. We create a composite index to compare religious faith in healing across race, gender, education, income denomination, and health status. Logistic regression predicts types of patients who believe God acts through physicians and those inclined to discuss spiritual concerns when ill. The most important findings are that: 80% of respondents believe God acts through physicians to cure illness, 40% believe God's will is the most important factor in recovery, and spiritual faith in healing is stronger among women. African-Americans, Evangelical Protestants, the poorer, sicker, and less educated. Those who believe that God acts through physicians are more likely to be African-American than White (OR = 1.9) and 55 or older (OR = 3.5). Those who discuss spiritual concerns with a physician are more likely to be female (OR = 1.9) and in poor health (OR = 2.1). Although 69% say they would want to speak to someone about spiritual concerns if seriously ill, only 3% would choose to speak to a physician. We conclude that religious faith in healing is prevalent and strong in the southern United States and that most people believe that God acts through doctors. Knowledge of the phenomena and variation across the population can guide inquiry into the spiritual concerns of patients.     

Escherichia coli O157:H7 infection in cows and calves in a beef cattle herd in Alberta,Canada

Escherichia coli O157:H7 infection of cows and calves in a naturally-infected beef cattle herd in Alberta, Canada, was investigated over 2 years, encompassing two calf production cycles. In both years of the study, E. coli O157:H7 was isolated from the faeces of cows shortly after but not before parturition in late winter: 6/38 (16%) in 1996 and 13/50 (26%) in 1997. At < 1 week post-partum, 13/52 (25%) calves born in 1997 were shedding the organism. Faecal shedding of E. coli O157:H7 by cows and calves continued over the 7 weeks that they were in the calving pens, with the organism being isolated from the faeces of 2-18% of cows and 23-26% of calves during this period. Five weeks after they were moved onto a native grass pasture, all the calves and all but one cow in 1997 had ceased shedding the organism. When the calves were weaned in the fall, E. coli O157:H7 was isolated from the faeces of 0-1.5% of the calves 1 week prior to weaning and from 6-14% of the calves within 2 weeks after weaning. Parturition, calving pens and weaning appear to be important factors in maintaining E. coli O157:H7 infections in this beef cattle herd. Isolates from cows and calves during the immediate post-partum period were mostly of the same pulsed-field gel electrophoresis (PFGE) type of E. coli O157:H7. Similarly, at weaning a common PFGE type of E. coli O157:H7, which differed slightly from the post-partum PFGE type, was isolated from the calves. These typing data suggest a common source of infection for the animals as well as demonstrate clonal turnover of resident populations of this pathogen.     

Human cytomegalovirus infection and expression in human malignant glioma

Malignant gliomas are the most common primary brain tumors in adults, have no known etiology, and are generally rapidly fatal despite current therapies. Human cytomegalovirus (HCMV) is beta-herpesvirus trophic for glial cells that persistently infects 50-90% of the adult human population. HCMV can be reactivated under conditions of inflammation and immunosuppression, and HCMV gene products can dysregulate multiple cellular pathways involved in oncogenesis. Here we show that a high percentage of malignant gliomas are infected by HCMV and multiple HCMV gene products are expressed in these tumors. These data are the first to show an association between HCMV and malignant gliomas and suggest that HCMV may play an active role in glioma pathogenesis.