Separation of electrocardiographic and encephalographic components based on signal averaging and wavelet shrinkage techniques

During ambulatory monitoring, it is often required to record the electroencephalogram (EEG) and the electrocardiogram (ECG) simultaneously. It would be ideal if both EEG and ECG can be obtained with one measurement. We introduce an algorithm combining the wavelet shrinkage and signal averaging techniques to extract the EEG and ECG components from an EEG lead signal to a noncephalic reference (NCR). The evaluation using simulation data and measured data showed that the normalized power spectrum unvaried in all frequency bands for the EEG components, and the sensitivity and specificity of R-wave detection for the ECG component were nearly 100%.     

A Human Papillomavirus (HPV) In Vitro Neutralization Assay That Recapitulates the In Vitro Process of Infection Provides a Sensitive Measure of HPV L2 Infection-Inhibiting Antibodies

Papillomavirus L2-based vaccines have generally induced low-level or undetectable neutralizing antibodies in standard in vitro assays yet typically protect well against in vivo experimental challenge in animal models. Herein we document that mice vaccinated with an L2 vaccine comprising a fusion protein of the L2 amino acids 11 to 88 of human papillomavirus type 16 (HPV16), HPV18, HPV1, HPV5, and HPV6 were uniformly protected from cervicovaginal challenge with HPV16 pseudovirus, but neutralizing antibodies against HPV16, -31, -33, -45, or -58 were rarely detected in their sera using a standard in vitro neutralization assay. To address this discrepancy, we developed a neutralization assay based on an in vitro infectivity mechanism that more closely mimics the in vivo infectious process, specifically by spaciotemporally separating primary and secondary receptor engagement and correspondingly by altering the timing of exposure of the dominant L2 cross-neutralizing epitopes to the antibodies. With the new assay, titers in the 100 to 10,000 range were measured for most sera, whereas undetectable neutralizing activities were observed with the standard assay. In vitro neutralizing titers measured in the serum of mice after passive transfer of rabbit L2 immune serum correlated with protection from cervicovaginal challenge of the mice. This “L2-based” in vitro neutralization assay should prove useful in critically evaluating the immunogenicity of L2 vaccine candidates in preclinical studies and future clinical trials.     

An animal model of cortical and callosal pathology in multiple sclerosis

The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.     

Factors predictive of the perceived osteoporosis–fracture link in fragility fracture patients

Objective

Given the asymptomatic nature of osteoporosis, a fragility fracture provides an opportunity to make the issue of osteoporosis relevant to patients. Patients who link their fragility fracture with osteoporosis are more likely to initiate osteoporosis treatment, yet to date, we know little about who is likely to make this link. This study examined whether demographic, health, and osteoporosis belief factors predicted a perceived link between a fragility fracture and osteoporosis.

Study design

This longitudinal cohort study analyzed baseline and follow up data collected as part of a provincial osteoporosis screening initiative targeting fragility fracture patients. Logistic regression analysis was used to examine the relationship between hypothesized predictors and the outcome.

Main outcome measure

Patient perception of the osteoporosis–fracture link at follow up.

Results

At baseline, 93% (1615/1735) of patients did not believe their fracture could have been caused by osteoporosis. Of these, only 8.2% changed this perception at follow up. Adjusted analyses showed that baseline characteristics associated with making the osteoporosis–fracture link at follow up were: a previous fracture (odds ratio (OR) 1.7, confidence interval (CI) 1.2–2.6), perception of osteoporosis pharmacotherapy benefits OR 1.2 (CI 1.0–1.5), diagnosis of rheumatoid arthritis OR 2.6 (CI 1.4–4.9) and the perception of bones as “thin” OR 8.2 (CI 5.1–13.1).

Conclusion

These results shed more light on patient-level barriers to osteoporosis management following an osteoporosis educational programme. They may be used to identify patients less likely to make the link between their fracture and osteoporosis and to inform interventions for this patient group.     

A Novel System to Study the Impact of Epithelial Barriers on Cellular Metabolism

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O₂)₂ 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm² for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society. PAC00: 8716Uv, 8715Vv     

Overt use of a tactile/kinaesthetic strategy shifts to covert processing in rehabilitation of letter-by-letter reading

Background: Letter-by-letter readers identify each letter of the word they are reading serially in left to right order before recognising the word. When their letter naming is also impaired, letter-by-letter reading is inaccurate and can render even single word reading very poor. Tactile and/or kinaesthetic strategies have been reported to improve reading in these patients, but only under certain conditions or for a limited set of stimuli.

Aims: The primary aim of the current study was to determine whether a tactile/kinaesthetic treatment could significantly improve reading specifically under normal reading conditions, i.e., reading untrained words presented in free vision and read without overt use of the strategy.

Methods & Procedures: Three chronic letter-by-letter readers participated in a tactile/kinaesthetic treatment aimed at first improving letter-naming accuracy (phase 1) and then letter-by-letter reading speed (phase 2). In a multiple case series design, accuracy and speed of reading untrained words without overt use of the trained tactile/kinaesthetic strategy was assessed before phase 1, after phase 1, and again after phase 2.

Outcomes & Results: All three patients significantly improved both their speed and accuracy in reading untrained words without overt use of the trained tactile/kinaesthetic strategy. All three patients required the additional practice in phase 2 to achieve significant improvement. Treatment did not target sentence-level reading, yet two of the three patients became so adept that they could read entire sentences.

Conclusions: This study replicates previous findings on the efficacy of tactile/kinaesthetic treatment for letter-by-letter readers with poor letter naming. It further demonstrates that this treatment can alter cognitive processing such that words never specifically trained can be read in free vision without overtly using the trained strategy. The data suggest that an important element in achieving this level of generalisation is continuing training beyond the point of initial mastery (i.e., accurate letter naming).     

Endovascular Exclusion of a Postendarterectomy Carotid Pseudoaneurysm

Carotid pseudoaneurysms are rare occurrences. They often result from trauma, but can also present following carotid endarterectomy. Treating such pseudoaneurysms can be difficult due to previous surgery and limited access to the high internal carotid artery. A case involving a postendarterectomy carotid pseudoaneurysm treated via a femoral approach with a covered stent using endoluminal techniques is presented.     

The underlying mechanisms of semantic memory loss in Alzheimer's disease and semantic dementia

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.     

Fatigue: The forgotten symptom of sleep apnea

Objective

The present investigation was designed to explore the role and implications of both daytime sleepiness and fatigue in obstructive sleep apnea syndrome with respect to sleep, perceived health quality, and psychological functioning.

Methods

Our participants consisted of two groups: 124 older community volunteers who completed a polysomnographic sleep study and were diagnosed with sleep apnea, and 19 healthy controls. All participants completed self-report measures of sleepiness, fatigue, sleep quality, health quality, and psychological functioning.

Results

The apnea sample was divided according to clinically relevant cut-offs on sleepiness and fatigue. When those with mid-range scores were ruled out, the following groups remained: low sleepiness/low fatigue (LL, n=23), high sleepiness/high fatigue (HH, n=28), high sleepiness/low fatigue (HS, n=10) and low sleepiness/high fatigue (HF, n=13). The respiratory disturbance index did not differ significantly among these groups and only the two highly fatigued groups (HH and HF) experienced significantly lower average oxygen saturation than the control group. Analyses revealed that the HH group was significantly worse than the LL and control groups on most sleep, health quality, and psychological measures. On these same measures, the groups for whom fatigue was low (LL and HS), regardless of sleepiness, were similar to controls.

Conclusion

When patients with sleep apnea are classified into different sleepiness/fatigue categories, the results show that high fatigue is associated with more severe dysfunction than high sleepiness. The current debate on whether to treat apnea patients with low sleepiness needs to consider the impact of fatigue.