Subtle pH variation around pH 4.0 affects aggregation kinetics and aggregate characteristics of recombinant human insulin

Insulin is a biotherapeutic protein, which, depending on environmental conditions such as pH, has been shown to form a large variety of aggregates with different structures and morphologies. This work focuses on the formation and characteristics of insulin particulates, dense spherical aggregates having diameters spanning from nanometre to low-micron size. An in-depth investigation of the system is obtained by applying a broad range of techniques for particle sizing and characterisation. An interesting observation was achieved regarding the formation kinetics and aggregate characteristics of the particulates; a subtle change in the pH from pH 4.1 to pH 4.3 markedly affected the kinetics of the particulate formation and led to different particulate sizes, either nanosized or micronsized particles. Also, a clear difference between the secondary structure of the protein particulates formed at the two pH values was observed, where the nanosized particulates had an increased content of aggregated β-structure compared to the micronsized particles. The remaining characteristics of the particles were identical for the two particulate populations. These observations highlight the importance of carefully studying the formulation design space and of knowing the impact of parameters such as pH on the aggregation to secure a drug product in control. Furthermore, the identification of particles only varying in few parameters, such as size, are considered highly valuable for studying the effect of particle features on the immunogenicity potential.Drug Delivery Technolog

Open Strings in Exactly Solvable Model of Curved Spacetime and PP-Wave Limit

In this paper we study the superstring version of the exactly solvable string model constructed by Russo and Tseytlin. This model represents superstring theory in a curved spacetime and can be seen as a generalization of the Melvin background. We investigate D-branes in this model as probes of the background geometry by constructing the boundary states. We find that spacetime singularities in the model become smooth at high energy from the viewpoint of open string. We show that there always exist bulk (movable) D-branes by the effect of electric flux. The model also includes Nappi-Witten model as the Penrose limit and supersymmetry is enhanced in the limit. We examine this phenomenon in the open string spectrum. We also find the similar enhancement of supersymmetry can be occurred in several coset models.Comment: Latex, 32 pages, typos corrected, references added, to appear in JHEP, eq.(2.22) correcte

Teoria și practica aderenței: manual pentru clinicieni

Adherence to antiretroviral (ARV) treatment during adolescence and young adulthood is a significant clinical issue for the current management of the HIV/AIDS epidemic in Romania. Understanding patients' own perceptions of their adherence behaviours and related psychological barriers is instrumental for developing robust interventions, and developing psychometrically sound instruments is essential for measuring adherence in this population. We adapted to Romanian an internationally validated questionnaire for the evaluation of ARV treatment adherence. We subsequently conducted a cross-sectional survey to examine its psychometric properties and investigate the relations between self-reported aspects of adherence and established indicators of adherence and health status: Pill count, doctor's assessment of patient's adherence and viral load. Results suggest that low self-reported adherence is particularly associated with experiencing side effects and emotional distress, as well as perceptions of high treatment difficulty and time demands, low self-efficacy, low treatment efficacy and low treatment satisfaction. Perceptions of improvements in health status were overall associated with increased adherence, but feeling good physically sometimes preceded non-adherence behaviours. The questionnaire proved psychometrically sound according to classical test theory criteria (e.g. Cronbach's α = 0.77, significant associations with adherence and health status indicators). Addressing adherence barriers in clinical practice with this population may help reduce their potential impact on behaviours

Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries

It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions—warmth and competence—plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges