Peptidoglycan recognition protein genes and risk of Parkinson's disease.

Increased gut permeability, inflammation, and colonic α-synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four PGLYRP genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 5'untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95%CI 0.4-0.9], CC OR 0.15 [95%CI 0.04-0.6]; log-additive P-trend, 0.0004). Common variants in PGLYRP genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD.

Head injury, α-synuclein Rep1, and Parkinson's disease.

OBJECTIVE: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk. METHODS: Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury. RESULTS: Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95-2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9-1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5-19; SEARCH OR, 2.3; 95% CI, 0.6-9.2; pooled OR, 3.5; 95% CI 1.4-9.2, p-interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03). INTERPRETATION: While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential.

Expedient synthesis and design strategies for new peptoid construction.

[reaction: see text] A range of peptoids can be prepared efficiently using microwave-assisted solid-phase chemistry in a commercial reactor. This method is most effective for the installation of electronically deactivated benzylic amines. The systematic incorporation of these amines into peptoids can deliver oligomers capable of displaying unique and stable structural motifs-microwave-assisted solid-phase synthesis will enable their future study and application.

Occupation and risk of parkinsonism: a multicenter case-control study.

BACKGROUND: We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. OBJECTIVE: To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. DESIGN: Case-control. SETTING: Eight movement disorders centers in North America. PARTICIPANTS: Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. MAIN OUTCOME MEASURES: This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis

Functional limitations and well-being in injured municipal workers: a longitudinal study.

Two instruments, the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36), were used to document both the immediate and short-term effects of workplace injuries in municipal workers. Telephone interviews were conducted up to 3 months following the injury. One hundred fourteen subjects agreed to participate in the study; 90 workers completed at least one useable interview. The relationship between functional limitation and lost days was evaluated using Cox proportional hazards models. At 3 months following the onset of injury, SF-36 scores for physical function, role-physical, and bodily pain differed significantly from population norms. Using one standard deviation of change, statistically significant hazard ratios were seen in subjects with lower SF-36 physical component summary, physical function, and bodily pain scores, and higher HAQ disability and fatigue scores. Functional limitations persisted in workers after relatively minor workplace injuries despite a 91% return to work rate.