A General Small-Angle X-ray Scattering-Based Screening Protocol for Studying Physical Stability of Protein Formulations

A fundamental step in developing a protein drug is the selection of a stable storage formulation that ensures efficacy of the drug and inhibits physiochemical degradation or aggregation. Here, we designed and evaluated a general workflow for screening of protein formulations based on small-angle X-ray scattering (SAXS). Our SAXS pipeline combines automated sample handling, temperature control, and fast data analysis and provides protein particle interaction information. SAXS, together with different methods including turbidity analysis, dynamic light scattering (DLS), and SDS-PAGE measurements, were used to obtain different parameters to provide high throughput screenings. Using a set of model proteins and biopharmaceuticals, we show that SAXS is complementary to dynamic light scattering (DLS), which is widely used in biopharmaceutical research and industry. We found that, compared to DLS, SAXS can provide a more sensitive measure for protein particle interactions, such as protein aggregation and repulsion. Moreover, we show that SAXS is compatible with a broader range of buffers, excipients, and protein concentrations and that in situ SAXS provides a sensitive measure for long-term protein stability. This workflow can enable future high-throughput analysis of proteins and biopharmaceuticals and can be integrated with well-established complementary physicochemical analysis pipelines in (biopharmaceutical) research and industry.

Working Memory Impairment in Transient Ischaemic Attack: N-back as a Sensitive Measure for Detection

Background: Transient ischaemic attack (TIA) can lead to lasting changes in brain structure and function resulting in cognitive impairment. Cognitive screening tools may lack sensitivity for detecting cognitive impairments, particularly executive function, which tends to be the earliest affected domain in vascular cognitive impairment. Aim: In this preliminary study, we examine a working memory (WMem) task as a sensitive measure of cognitive impairment in TIA. Method: Patients referred to a TIA clinic for transient neurological symptoms completed a general cognitive screening tool (Montreal Cognitive Assessment; MoCA), and a WMem task (2-N-back) in a cross-sectional design. Results: TIA patients (n = 12) showed significantly reduced WMem performance on the N-back compared to patients diagnosed with mimic clinical conditions with overlapping symptoms (n = 16). No group differences were observed on the MoCA. Conclusions: Assessing WMem may provide a sensitive measure of cognitive impairment after TIA, with implications for cognitive screening in TIA services to triage patients for further neuropsychological support, or for interventions to prevent vascular dementia.

Energy and Exhaustion May Explain Different Subdomains of Perceived Fatigability

Fatigability is a more sensitive measure of one’s perception of fatigue. To identify an appropriate fatigue question when a fatigability measure is unavailable, we examined associations between widely used global fatigue questions and perceived physical and mental fatigability. Participants (N=896, age=74.7±6.6, 58.1% women) from two aging research registries completed the valid Pittsburgh Fatigability Scale (PFS, 0-50) and five global fatigue questions: energy level (0-10), running out of energy (0-5), feeling energetic (0-6), feeling tired (0-6), and feeling exhausted (0-6) over past four weeks. All fatigue measures were correlated (p<0.0001) with physical (|r| range=0.48-0.57) and mental fatigability (|r| range=0.31-0.39). “Energy level” and “feeling exhausted” had strongest associations with physical and mental fatigability, respectively, in age, sex, BMI-adjusted regression models (p’s<0.001), suggesting older adults can distinguish between physical and mental domains. Future work will explore how these constructs are distinct but related, and confirm the optimal proxy for the two fatigability subdomains.

Analisis Sensitivitas Respon Mahasiswa Terhadap Perluasan Merek Shampo Lifebuoy

The purpose of this study was to determine the level of sensitivity of students to brand expansion of Lifebuoy shampoo at the State University of Padang and to find out the direction of the response of UNP students to brand expansion of Lifebuoy shampoo. This type of research is a survey with a descriptive approach. The population of this research is the students of Padang State University (UNP). The sample in this study was based on the Chocran formula as many as 100 respondents who were selected using the Non-Probability sampling method and purposive sampling technique. Using primary data obtained through distributing questionnaires to UNP students with certain criteria. The method used is the analysis of the direction of the consumer's response by calculating the strength of the response and stimuli as well as the sensitivity analysis of the response. The results showed that (1) The sensitivity of the response of UNP students from bar soap to lifebuoy shampoo was 2.41. because the size of this sensitivity is greater than 1, the sensitivity is considered a sensitive measure. (2) the response strength of UNP students from Lifebuoy bath soap to Lifebuoy brand shampoo is negative 157. Keywords : brand extension, sensitivity, direction of response