Surface-mediated spontaneous emulsification of the acylated peptide, semaglutide.

Acylated peptides composed of glucagon-like peptide-1 receptor agonists modified with a fatty acid side chain are an important class of therapeutics for type 2 diabetes and obesity but are susceptible to an unusual physical instability in the presence of hydrophobic surfaces, i.e., spontaneous emulsification, also known as ouzo formation in practice.

Micelle Formation and Phase Separation of Poloxamer 188 and Preservative Molecules in Aqueous Solutions Studied by Small Angle X-ray Scattering.

Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution.

Aggregation Kinetics of Polysorbate 80/-Cresol Solutions: A Small-Angle Neutron Scattering Study.

Polysorbate 80 (PS80), a nonionic surfactant used in pharmaceutical formulation, is known to be incompatible with -cresol, an antimicrobial agent for multi-dose injectable formulations. This incompatibility results in increased turbidity caused by micelle aggregation progressing over weeks or longer, where storage temperature, ionic strength, and component concentration influence the aggregation kinetics. Small-angle neutron scattering (SANS) analysis of PS80/-cresol solutions over a pharmaceutically relevant concentration range of each component reveals the cause of aggregation, the coalescence mechanism, and aggregate structure.

Preservative Induced Polysorbate 80 Micelle Aggregation.

Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology.

Development of an avian avulavirus 1 (AAvV-1) L-gene real-time RT-PCR assay using minor groove binding probes for application as a routine diagnostic tool.

Newcastle disease is a devastating disease of poultry caused by Newcastle disease virus (NDV), a virulent form of avian avulavirus 1 (AAvV-1). A rapid, sensitive and specific means for the detection of NDV is fundamental for the control of this notifiable transboundary virus. Although several real-time RT-PCR assays exist for the detection of AAvV-1, diagnostic sensitivity and specificities can be sub-optimal.

Altered premotor cortical oscillations during repetitive movement in persons with Parkinson's disease.

Premotor areas play a critical role in the control of repetitive movements. While research has shown that movement-related oscillations are abnormal during repetitive movements in persons with Parkinson's disease (PD), there is limited research examining the contribution of premotor areas, such as the contralateral dorsal premotor area (PMd) and supplementary motor area (SMA), to this impairment. This study compared movement-related oscillations over premotor regions between participants with PD and control participants.

Motor cortical oscillations are abnormally suppressed during repetitive movement in patients with Parkinson's disease.

Objective: Impaired repetitive movement in persons with Parkinson's disease (PD) is associated with reduced amplitude, paradoxical hastening and hesitations or arrest at higher movement rates. This study examined the effects of movement rate and medication on movement-related cortical oscillations in persons with PD.

Methods: Nine participants with PD were studied off and on medication and compared to nine control participants.

Early and unintentional release of planned motor actions during motor cortical preparation.

Voluntary movements are often preceded by a movement-related potential beginning as much as two seconds prior to the onset of movement. In light of evidence that motor actions can be prepared and initiated in less than 200 ms, the function of this early activity has remained enigmatic. We hypothesized that the movement-related potential reflects the state of preparation of the planned movement.

Rate-dependent impairments in repetitive finger movements in patients with Parkinson's disease are not due to peripheral fatigue.

Performance of repetitive finger movements is an important clinical measure of disease severity in patients with Parkinson's disease (PD) and is associated with a dramatic deterioration in performance at movement rates near 2 Hz and above. The mechanisms contributing to this rate-dependent movement impairment are poorly understood. Since clinical and experimental testing of these movements involve prolonged repetition of movement, a loss of force-generating capacity due to peripheral fatigue may contribute to performance deterioration.

Suppression of deep brain stimulation artifacts from the electroencephalogram by frequency-domain Hampel filtering.

Objective: Currently, electroencephalography (EEG) cannot be used to record cortical activity during clinically effective DBS due to the presence of large stimulation artifact with components that overlap the useful spectrum of the EEG. A filtering method is presented that removes these artifacts whilst preserving the spectral and temporal fidelity of the underlying EEG.

Methods: The filter is based on the Hampel identifier that treats artifacts as outliers in the frequency domain and replaces them with interpolated values.

Time-frequency analysis of movement-related spectral power in EEG during repetitive movements: a comparison of methods.

During dynamic voluntary movements, power in the alpha- and beta-bands resulting from synchronized neuronal activity is modulated in a manner that is time-locked to movement onset. These signals can be readily recorded from the scalp surface using electroencephalography. Abnormalities in the magnitude and timing of these oscillations are present in a wide variety of movement disorders including Parkinson's disease and dystonia.

A frequency domain Hampel filter for blind rejection of sinusoidal interference from electromyograms.

A frequency domain filtering method is presented for the removal of power-line and other sinusoidal interference from electromyograms. The presence of such interference results in spikes in the complex-valued fast Fourier transform which can be considered to be outliers. The filter uses the outlier-robust Hampel identifier to detect spikes and replaces them with the median value of local values.