Bereitschaftspotential in Multiple System Atrophy.

Objective: Multiple system atrophy (MSA) is a neurodegenerative disorder manifesting as parkinsonism, cerebellar ataxia, and autonomic dysfunction. It is categorized into MSA with predominant parkinsonism (MSA-P) and into MSA with predominant cerebellar ataxia (MSA-C). The pathophysiology of motor control circuitry involvement in MSA subtype is unclear. Bereitschaftspotential (BP) is a feasible clinical tool to measure electroencephalographic activity prior to volitional motions. We recorded BP in patients with MSA-P and MSA-C to investigate their motor cortical preparation and activation for volitional movement. Methods: We included eight patients with MSA-P, eight patients with MSA-C, and eight age-matched healthy controls. BP was recorded during self-paced rapid wrist extension movements. The electroencephalographic epochs were time-locked to the electromyography onset of the voluntary wrist movements. The three groups were compared with respect to the mean amplitudes of early (1,500-500 ms before movement onset) and late (500-0 ms before movement onset) BP. Results: Mean early BP amplitude was non-significantly different between the three groups. Mean late BP amplitude in the two patient groups was significantly reduced in the parietal area contralateral to the movement side compared with that in the healthy control group. In addition, the late BP of the MSA-C group but not the MSA-P group was significantly reduced at the central parietal area compared with that of the healthy control group. Conclusions: Our findings suggest that patients with MSA exhibit motor cortical dysfunction in voluntary movement preparation and activation. The dysfunction can be practicably evaluated using late BP, which represents the cerebello-dentato-thalamo-cortical pathway.

Mortality and morbidity associated with ambient temperatures in Taiwan.

BACKGROUND: This study evaluated integrated risks of all-cause mortality, emergency room visits (ERVs), and outpatient visits associated with ambient temperature in all cities and counties of Taiwan. In addition, the modifying effects of socio-economic and environmental factors on temperature-health associations were also evaluated. METHODS: A distributed lag non-linear model was applied to estimate the cumulative relative risks (RRs) with confidence intervals of all-cause mortality, ERVs, and outpatient visits associated with extreme temperature events. Random-effect meta-analysis was used to estimate the pooled RR of all-cause mortality, ERVs, and outpatient visits influenced by socio-economic and environmental factors. RESULTS: Temperature-related risks varied with study area and health outcome. Meta-analysis showed greater all-cause mortality risk occurred in low temperatures than in high temperatures. Integrated RR of all-cause mortality was 1.71 (95% confidence interval [CI]:1.43-2.04) in the 5th percentile temperature and 1.10 (95% CI: 1.05-1.15) in the 95th percentile temperature, while the lowest mortality risk was in the 60th percentile temperature (22.2 °C). Risk for ERVs increased when temperature increased (RR was 1.21 [95% CI: 1.17-1.26] in 95th percentile temperature), but risk of outpatient visits increased at low temperatures (RR was 1.06 [95% CI: 1.01-1.12] in the 5th percentile temperature). Certain socio-economic factors significantly modified low-temperature-related mortality risks, including number of employed populations, elders living alone from lower-income families, and public and medical services. CONCLUSIONS: This study found that mortality and outpatient visits were higher at low temperature, while ERVs risk was higher at high temperature. Future plans for public health and emerging medical services responding to extreme temperatures should consider regional and integrated evaluations of temperature-related health risks and modifying factors.

In silico analysis reveals sequential interactions and protein conformational changes during the binding of chemokine CXCL-8 to its receptor CXCR1.

Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR) family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD) simulations. A multi-steps binding mode is proposed: (i) the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii) hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR) motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii) electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.