Shear stress induced stimulation of mammalian cell metabolism

A flow apparatus was developed for the study of the metabolic response of anchorage dependent cells to a wide range of steady and pulsatile shear stresses under well controlled conditions. Human umbilical vein endothelial cell monolayers were subjected to steady shear stresses of up to 24 dynes/sq cm, and the production of prostacyclin was determined. The onset of flow led to a burst in prostacyclin production which decayed to a long term steady state rate (SSR). The SSR of cells exposed to flow was greater than the basal release level, and increased linearly with increasing shear stress. It is demonstrated that shear stresses in certain ranges may not be detrimental to mammalian cell metabolism. In fact, throughout the range of shear stresses studied, metabolite production is maximized by maximizing shear stress

Synchronised neural signature of creative mental imagery in reality and augmented reality

Creativity, transforming imaginative thinking into reality, is a mental imagery simulation in essence. It can be incorporeal, concerns sophisticated and/or substantial thinking, and involves objects. In the present study, a mental imagery task consisting of creating a scene using familiar (FA) or abstract (AB) physical or virtual objects in real (RMI) and augmented reality (VMI) environments, and an execution task involving effectively creating a scene in augmented reality (VE), were utilised. The beta and gamma neural oscillations of healthy participants were recorded via a 32 channel wireless 10/20 international EGG system. In real and augmented environments and for both the mental imagery and execution tasks, the participants displayed a similar cortico-cortical neural signature essentially based on synchronous vs asynchronous beta and gamma oscillatory activities between anterior (i.e. frontal) and posterior (i.e. parietal, occipito-parietal and occipito-temporal) areas bilaterally. The findings revealed a transient synchronised neural architecture that appears to be consistent with the hypothesis according to which, creativity, because of its inherent complexity, cannot be confined to a single brain area but engages various interconnected networks

The design of an optimal Bonus-Malus System based on the Sichel distribution

This chapter presents the design of an optimal Bonus-Malus System (BMS) using the Sichel distribution to model the claim frequency distribution. This system is proposed as an alternative to the optimal BMS obtained by the traditional Negative Binomial model [19]. The Sichel distribution has a thicker tail than the Negative Binomial distribution and it is considered as a plausible model for highly dispersed count data. We also consider the optimal BMS provided by the Poisson-Inverse Gaussian distribution (PIG), which is a special case of the Sichel distribution. Furthermore, we develop a generalised BMS that takes into account both the a priori and a posteriori characteristics of each policyholder. For this purpose we consider the generalised additive models for location, scale and shape (GAMLSS) in order to use all available information in the estimation of the claim frequency distribution. Within the framework of the GAMLSS we propose the Sichel GAMLSS for assessing claim frequency as an alternative to the Negative Binomial Type I (NBI) regression model used by Dionne and Vanasse [9, 10]. We also consider the NBI and PIG GAMLSS for assessing claim frequency

Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle

Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of “virulence factors” important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis

Flow-Dependent Mass Transfer May Trigger Endothelial Signaling Cascades

It is well known that fluid mechanical forces directly impact endothelial signaling pathways. But while this general observation is clear, less apparent are the underlying mechanisms that initiate these critical signaling processes. This is because fluid mechanical forces can offer a direct mechanical input to possible mechanotransducers as well as alter critical mass transport characteristics (i.e., concentration gradients) of a host of chemical stimuli present in the blood stream. However, it has recently been accepted that mechanotransduction (direct mechanical force input), and not mass transfer, is the fundamental mechanism for many hemodynamic force-modulated endothelial signaling pathways and their downstream gene products. This conclusion has been largely based, indirectly, on accepted criteria that correlate signaling behavior and shear rate and shear stress, relative to changes in viscosity. However, in this work, we investigate the negative control for these criteria. Here we computationally and experimentally subject mass-transfer limited systems, independent of mechanotransduction, to the purported criteria. The results showed that the negative control (mass-transfer limited system) produced the same trends that have been used to identify mechanotransduction-dominant systems. Thus, the widely used viscosity-related shear stress and shear rate criteria are insufficient in determining mechanotransduction-dominant systems. Thus, research should continue to consider the importance of mass transfer in triggering signaling cascades

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

Skin Cancer:Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches

Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice