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.     

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     

Analysis of spike-wave discharges in rats using discrete wavelet transform

A feature is a distinctive or characteristic measurement, transform, structural component extracted from a segment of a pattern. Features are used to represent patterns with the goal of minimizing the loss of important information. The discrete wavelet transform (DWT) as a feature extraction method was used in representing the spike-wave discharges (SWDs) records of Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. The SWD records of WAG/Rij rats were decomposed into time-frequency representations using the DWT and the statistical features were calculated to depict their distribution. The obtained wavelet coefficients were used to identify characteristics of the signal that were not apparent from the original time domain signal. The present study demonstrates that the wavelet coefficients are useful in determining the dynamics in the time-frequency domain of SWD records.     

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%.     

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.     

An in vivo database model for pharmacological and physiological dosage for experimental animals

We developed a database compiling in vivo doses of compounds for various activities in certain animal species. The related database covers almost 100 years of experiments. The conceptual scheme of the database was created using concepts of the entity-relationship modeling principles. Using published references, dosages and their effects on laboratory animals were entered as data. As the next stage of our work, we have started to examine the available literature to information about the experimental dosages of various drugs used in other studies.The database provides various interfaces, including graphical-user interfaces and interfaces for Internet access. The database will be useful as a knowledge infrastructure for researchers who have to perform dose-scan experiments for a specific pharmacological activity. The basic benefit of that knowledge infrastructure is that it will enable virtual pharmacological experiments that will be considerably less expensive than conventional laboratory experiments, because the number of animals used and the number of dose-scan experiments will be greatly reduced. The developed database will also be helpful for new drug development studies and for responding to queries about animal types, drugs used, drug interactions, and results.     

Review of the Nutritional Implications of Farmers' Markets and Community Gardens: A Call for Evaluation and Research Efforts

The development and promotion of farmers' markets and community gardens is growing in popularity as a strategy to increase community-wide fruit and vegetable consumption. Despite large numbers of farmers' markets and community gardens in the United States, as well as widespread enthusiasm for their use as a health promotion tool, little is known about their influcence on dietary intake. This review examines the current scientific literature on the implications of farmers' market programs and community gardens on nutrition-related outcomes in adults. Studies published between January 1980 and January 2009 were identified via PubMed and Agricola database searches and by examining reference lists from relevant studies. Studies were included in this review if they took place in the United States and qualitatively or quantitatively examined nutrition-related outcomes, including dietary intake; attitudes and beliefs regarding buying, preparing, or eating fruits and vegetables; and behaviors and perceptions related to obtaining produce from a farmers' market or community garden. Studies focusing on garden-based youth programs were excluded. In total, 16 studies were identified for inclusion in this review. Seven studies focused on the impact of farmers' market nutrition programs for Special Supplemental Nutrition Program for Women, Infants, and Children participants, five focused on the influence of farmers' market programs for seniors, and four focused on community gardens. Findings from this review reveal that few well-designed research studies (eg, those incorporating control groups) utilizing valid and reliable dietary assessment methods to evaluate the influence of farmers' markets and community gardens on nutrition-related outcomes have been completed. Recommendations for future research on the dietary influences of farmers' markets and community gardens are provided.     

PERIOD2 Variants Are Associated with Abdominal Obesity, Psycho-Behavioral Factors, and Attrition in the Dietary Treatment of Obesity

The purpose of this research was to test for association between polymorphisms in the circadian clock-related gene PERIOD2 (PER2) and attrition in patients prone to withdrawal from a behavioral weight-reduction program based on the Mediterranean diet. A total of 454 overweight/obese participants (women=380, men=74), aged 20 to 65 years, who attended outpatient clinics specializing in obesity between January and December 2008, were studied. Anthropometric, biochemical, and dietary-intake variables were analyzed. Effectiveness of the program was assessed, and a questionnaire of barriers to weight loss was considered. Multivariate analysis and logistic regression models were performed. Results indicate that PER2 polymorphisms rs2304672C>G and rs4663302C>T were associated with abdominal obesity (P<0.05). Participants who withdrew from treatment were significantly more obese and had more barriers to lose weight (P<0.05). They also displayed a lower likelihood of planning eating in advance and experiencing stress with dieting than those who completed treatment. Frequency of rs4663307 minor allele was significantly greater in withdrawers than in those who successfully completed treatment (P<0.05). Logistic regression analysis showed that rs2304672 C>G minor allele carriers had a greater probability of dropping out, displaying extreme snacking, experiencing stress with dieting, eating when bored, and skipping breakfast than noncarriers. PER2 is implicated in attrition in weight-loss treatment and may modulate eating-behavior-related phenotypes. These findings could represent a step toward personalized health care and nutrition based on a combination of genotyping and psycho-behavioral characterization.     

Mediation Analyses: Applications in Nutrition Research and Reading the Literature

Mediation analysis is a newer statistical tool that is becoming more prominent in nutrition research. Its use provides insight into the relationship among variables in a potential causal chain. For intervention studies, it can define the influence of different programmatic components and, in doing so, allows investigators to identify and refine a program's critical aspects. We present an overview of mediation analysis, compare mediators with other variables (confounders, moderators, and covariates), and illustrate how mediation analysis permits interpretation of the change process. A framework is outlined for the critical appraisal of articles purporting to use mediation analysis. The framework's utility is demonstrated by searching the nutrition literature and identifying articles citing mediation cross referenced with the terms “nutrition,” “diet,” “food,” and “obesity.” Seventy-two articles were identified that involved human subjects and behavior outcomes, and almost half mentioned mediation without tests to define its presence. Tabulation of the 40 articles appropriately assessing mediation demonstrates an increase in these techniques' appearance and the breadth of nutrition topics addressed. Mediation analysis is an important new statistical tool. Familiarity with its methodology and a framework for assessing articles will allow readers to critically appraise the literature and make informed independent evaluations of works using these techniques.