Automatic assessment of levodopa-induced dyskinesias in daily life by neural networks.

We developed an objective and automatic procedure to assess the severity of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease during daily life activities. Thirteen patients were continuously monitored in a home-like situation for a period of approximately 2.5 hours. During this time period, the patients performed approximately 35 functional daily life activities. Behavior of the patients was measured using triaxial accelerometers, which were placed at six different positions on the body. A neural network was trained to assess the severity of LID using various variables of the accelerometer signals. Neural network scores were compared with the assessment by physicians, who evaluated the continuously videotaped behavior of the patients off-line. The neural network correctly classified dyskinesia or the absence of dyskinesia in 15-minute intervals in 93.7, 99.7, and 97.0% for the arm, trunk, and leg, respectively. In the few cases of misclassification, the rating by the neural network was in the class next to that indicated by the physicians using the AIMS score (scale 0-4). Analysis of the neural networks revealed several new variables, which are relevant for assessing the severity of LID. The results indicate that the neural network can accurately assess the severity of LID and could distinguish LID from voluntary movements in daily life situations.     

Can a part of an inducer become incorporated into interferon?

Highly purified and concentrated interferons obtained from L cells or from mouse peritoneal leukocytes (MPL) after induction with³H-uridin labeled double-stranded RNA of f₂ phageE. coli (phage ds-RNA) were analysed by poly-acrylamide gel electrophoresis. A coincidence of the discrete radioactivity peak with one of the interferon activity peaks was demonstrated.     

BAG1 over-expression in brain protects against stroke

The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases.     

HIV testing within at-risk populations in the United States and the reasons for seeking or avoiding HIV testing

OBJECTIVES: We determined proportions of high-risk persons tested for HIV, the reasons for testing and not testing, and attitudes and perceptions regarding HIV testing, information that is critical for planning prevention programs. METHODS: Cross-sectional interview study of persons at high risk for HIV infection (men who have sex with men [MSM]; injection drug users [IDUs]; and heterosexual persons recruited from gay bars, street outreach, and sexually transmitted disease clinics) among six states participating in the HIV Testing Survey (HITS) in 1995 to 1996 (HITS-I) and 1998 to 1999 (HITS-II). RESULTS: Overall testing rates were lower in the HITS-I (1226/1599 [77%]) than in the HITS-II (1375/1711 [80%]) (p =.01). Persons <25 years old tested less frequently than those >or=25 years old (HITS-I: 71% vs. 78%, respectively, p=.007; HITS-II: 63% vs. 85%, respectively, p<.001). The main reasons for testing and not testing were the same in both surveys, but the proportions of reasons for not testing differed (e.g., "unlikely exposed to HIV" [HITS-I (17%) vs. HITS-II (30%), p<.0001], "afraid of finding out HIV-positive" [HITS-I (27%) vs. HITS-II (18%), p<.0001]). Attitudes regarding HIV testing differed among tested and untested respondents, especially among MSM. CONCLUSIONS: HIV testing rates were higher in the HITS-II, but testing rates decreased among the youngest respondents. Denial of HIV risk factors and fear of being HIV-positive were the principal reasons for not being tested. Availability of new HIV therapies may have contributed to decreased fear of finding out that one is HIV infected as a reason to avoid testing. The increased proportion of persons at risk who did not test because they believed they were unlikely to have been exposed highlights the need for prevention efforts to address risk perceptions.     

Influence of outdoor aeroallergens on hospitalization for asthma in Canada

BACKGROUND: The risk of hospitalization for asthma caused by outdoor aeroallergens is largely unknown. OBJECTIVE: The objective of this study was to determine the association between changes in outdoor aeroallergens and hospitalizations for asthma from the Pacific coast to the Atlantic coast of Canada. METHODS: A daily time series analysis was done to test the association between daily changes in aeroallergens and daily changes in hospitalizations for asthma during a 7-year period between 1993 and 2000 in 10 of the largest cities in Canada. Results were adjusted for long-term trends, day of the week, climate, and air pollution. RESULTS: A daily increase, equivalent to the mean value of each allergen, was associated with the following percentage increase in asthma hospitalizations: 3.3% (95% CI, 2.3 to 4.1) for basidiomycetes, 3.1% (95% CI, 2.8 to 5.7) for ascomycetes, 3.2% (95% CI, 1.6 to 4.8) for deuteromycetes, 3.0% (95% CI, 1.1 to 4.9) for weeds, 2.9% (95% CI, 0.9 to 5.0) for trees, and 2.0% (95% CI, 1.1 to 2.8) for grasses. After accounting for the independent effects of trees and ozone, the combination of the 2 was associated with an additional 0.22% increase in admissions averaged across cities (P <.05). CONCLUSION: These findings provide evidence for the hypothesis that aeroallergens are an important cause of severe asthma morbidity across Canada, and in some situations there might be a modest synergistic adverse effect of ozone and aeroallergens combined.     

Menstrual Cycle Phase is a Potential Confound in Psychophysiology Research

Effects of menstrual cycle phase on physiological levels and reactivity were studied in a withinsubject design with 20 women aged 18–30 years. Basal body temperature was monitored daily; follicular and luteal recording sessions occurred before and after the ovulatory temperature rise, respectively. The design consisted of task and rest periods, presented in counterbalanced order across phases. Half the subjects began during their follicular phase and half began during their luteal phase. Follicular and luteal phases were compared for differences between baseline resting levels, as well as for reactivity. The results showed menstrual phase differences in heart rate, pulse transit time, and EEG alpha, particularly during tasks, but no difference in reactivity. Habituation effects in the group that began during the follicular phase often masked luteal activation. In spite of the fact that not all statistical results achieved significance, the consistency of most trends supports the conclusion that physiological recording sessions with women might best be restricted to the follicular phase.     

CpG motifs of DNA vaccines induce the expression of chemokines and MHC class II molecules on myocytes

Determining how an immune response is initiated after in vivo transfection of myocytes with plasmids encoding foreign antigens is essential to understand the mechanisms of intramuscular (i. m.) genetic immunization. Since myocytes are facultative antigen-presenting cells lacking MHC class II and co-stimulatory molecules, it was assumed that their unique role upon DNA vaccination is to synthesize and secrete the protein encoded by the plasmid. Here we describe that i. m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes. Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes. A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific T cells. These findings suggest that one mechanism for the immunogenicity of DNA vaccines consists in the presentation of peptides to CD4 T cells by in vivo plasmid-transfected myocytes.