Development of a Highly Differentiated Human Primary Proximal Tubule MPS Model (aProximate MPS Flow)

\ua9 2023 by the authors.The kidney proximal tubule (PT) mediates renal drug elimination in vivo and is a major site of drug-induced toxicity. To reliably assess drug efficacy, it is crucial to construct a model in which PT functions are replicated. Current animal studies have proven poorly predictive of human outcome. To address this, we developed a physiologically relevant micro-physiological system (MPS) model of the human PT, the aProximate MPS Flow platform (Patent No: G001336.GB). In this model, primary human PT cells (hPTCs) are subjected to fluidic media flow and a shear stress of 0.01–0.2 Pa. We observe that these cells replicate the polarity of hPTCs and exhibit a higher expression of all the key transporters of SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A2 (OCT2), SLC47A1 (MATE1), SLC22A12 (URAT1), SLC2A9 (GLUT9), ABCB1 (MDR1), ABCC2 (MRP2), LRP2 (megalin), CUBN (cubilin), compared with cells grown under static conditions. Immunofluorescence microscopy confirmed an increase in OAT1, OAT3, and cilia protein expression. Increased sensitivity to nephrotoxic protein cisplatin was observed; creatinine and FITC-albumin uptake was significantly increased under fluidic shear stress conditions. Taken together, these data suggest that growing human PT cells under media flow significantly improves the phenotype and function of hPTC monolayers and has benefits to the utility and near-physiology of the model

Organ-on-a-Chip: Design and Simulation of Various Microfluidic Channel Geometries for the Influence of Fluid Dynamic Parameters

Shear stress, pressure, and flow rate are fluid dynamic parameters that can lead to changes in the morphology, proliferation, function, and survival of many cell types and have a determinant impact on tissue function and viability. Microfluidic devices are promising tools to investigate these parameters and fluid behaviour within different microchannel geometries. This study discusses and analyses different designed microfluidic channel geometries regarding the influence of fluid dynamic parameters on their microenvironment at specified fluidic parameters. The results demonstrate that in the circular microchamber, the velocity and shear stress profiles assume a parabolic shape with a maximum velocity occurring in the centre of the chamber and a minimum velocity at the walls. The longitudinal microchannel shows a uniform velocity and shear stress profile throughout the microchannel. Simulation studies for the two geometries with three parallel microchannels showed that in proximity to the micropillars, the velocity and shear stress profiles decreased. Moreover, the pressure is inversely proportional to the width and directly proportional to the flow rate within the microfluidic channels. The simulations showed that the velocity and wall shear stress indicated different values at different flow rates. It was also found that the width and height of the microfluidic channels could affect both velocity and shear stress profiles, contributing to the control of shear stress. The study has demonstrated strategies to predict and control the effects of these forces and the potential as an alternative to conventional cell culture as well as to recapitulate the cell- and organ-specific microenvironment

Variation in growth rates of branching corals along Australia's Great Barrier Reef

Coral growth is an important component of reef health and resilience. However, few studies have investigated temporal and/or spatial variation in growth of branching corals, which are important contributors to the structure and function of reef habitats. This study assessed growth (linear extension, density, and calcification) of three branching coral species (Acropora muricata, Pocillopora damicornis and Isopora palifera) at three distinct locations (Lizard Island, Davies/Trunk Reef, and Heron Island) along Australia’s Great Barrier Reef (GBR). Annual growth rates of all species were highest at Lizard Island and declined with increasing latitude, corresponding with differences in temperature. Within locations, however, seasonal variation in growth did not directly correlate with temperature. Between October 2012 and October 2014, the highest growth of A. muricata was in the 2013–14 summer at Lizard Island, which was unusually cool and ~0.5 °C less than the long-term summer average temperature. At locations where temperatures reached or exceeded the long-term summer maxima, coral growth during summer periods was equal to, if not lower than, winter periods. This study shows that temperature has a significant influence on spatiotemporal patterns of branching coral growth, and high summer temperatures in the northern GBR may already be constraining coral growth and reef resilience

Downside: The perpetrator of violence in the representations of social and health professionals

Gender-based violence is a widespread phenomenon and pandemic that affects women’s lives. Many interventions have been activated for perpetrators, but the dropout rate is still high. In order to draw up guidelines for responsibly and sustainably dealing with the phenomenon, this study is aimed at investigating the professionals’ perception of the perpetrator as a useful element in designing innovative intervention policies. Open interviews were carried out with welfare and health professionals and the Grounded Theory Methodology was used to analyze the collected data. These results detect attitudes of social health personnel and their feelings of impotence towards gender-based perpetrators because of the emergence of an inevitable repetitiveness of the violent behavior, as well as the “normality of violence” in a patriarchal culture and its “transversality”. This reflective knowledge allows for the opportunity to develop best transformative attitudes toward the phenomenon. According to the results, it is urgent to establish an active and convinced alliance with the healthy part of the man, through specific prevention paths, in order to activate an authentic motivation for change and its sustainability

Materials analysis and image-based modelling of transmissibility and strain behaviour in approved face mask microstructures

Data availability: The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.Copyright © The Author(s) 2022. Comparisons are made between six different approved face masks concerning their particle transmissibility allied to mechanical properties. The latter involves material testing and stretch or strain behaviour under load. SEM and X-ray elemental analyses showed contrasting structures between random and ordered fibre orientations. These constitute the mask designs where transmissibility is to be minimised. Airflow velocity measurement enabled filtration to be measured between the different mask designs, from two to six layers of different fabrics in combination. SEM provided the fibre diameter and pore size of each mask layer, up to a maximum of six. Stretching each complete mask showed its elasticity and recovery behaviour on an energy basis. The energy conversion involved in mask straining involves areas enclosed within steady and cyclic load-extension plots. Thus, the work done in extending a mask and the energy recovered from its release identified a hysteresis associated with an irrecoverable permanent stretch to the mask fabric. Failure of individual layers, which occurred successively in extended stretch tests, appeared as a drop in a load-extension response. That change is associated with permanent damage to each mask and friction contact within the rearrangement of loose fibre weaves. Masks with the greatest number of layers reduced particle transmissibility. However, woven or ordered mask fabrics in two layers with different orientations provided comparable performance. Simulation of each mechanical response, velocity streamlining and fibre distribution within the mask layers are also presented.Design Department at Brunel University London

Filtering Efficiency and Design Properties of Medical- and Non-Medical-Grade Face Masks: A Multiscale Modeling Approach

Data Availability Statement: The data presented in this study are available on request from the corresponding author due to privacy and ethical restrictions.Approved medical face masks have been shown to prevent the spread of respiratory droplets associated with coronavirus transmission in specific settings. The primary goal of this study was to develop a new strategy to assess the filtering and transmissibility properties of medical- and non-medical-grade face masks. In this study, we designed and assessed the filtering efficiency of particles through six different masks with a diverse set of fabrics, textures (woven and non-woven), fiber diameters, and porosity. The filtering and transmissibility properties of face mask layers individually and in combination have been assessed using mathematical analyses and new experimental data. The latter provided velocity profiles and filtration efficiencies for which the data were shown to be predictable. The filtration efficacy and pressure drop across each fabric have been tested using an aerosol particle spray and scanning electron microscopy. To assess clinical significance, the temperature and humidity of the masks were tested on a group of healthy volunteers spanning various age ranges (9–79 years old), utilizing an embedded temperature sensor disc. Also, a mask filter model was developed using fluid dynamic simulations (Solidworks Flow) to evaluate the aerodynamic dispersion of respiratory droplets. Overall, the FFP2 and FFP3 masks demonstrated the highest filtration efficiencies, each exceeding 90%, a feature of multi-layered masks that is consistent with simulations demonstrating higher filtering efficiencies for small particles (<5 µm). The velocity and temperature simulations of all six masks revealed a low air velocity (~1 m/s) inside the mask and a temperature variation of approximately 3 °C during the breathing cycle.No funding was received for conducting this study

High exposure to advanced glycation End-products could facilitate the occurrence of pediatric Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a major cause of upper gastrointestinal morbidity in the pediatric age. It has been hypothesized that the interaction between genetic and environmental factors (i.e., dietary habits) may induce the development of EoE. Among dietary factors, it has been postulated that advanced glycation end-products (AGEs), present at high level in ultra-processed foods (UPFs), could be involved in the pathogenesis of several inflammatory diseases, including food allergy. AGEs are ligands to the RAGE receptor and, mimicking signals provoked by tissue damage, are capable to increase tissue permeability, inflammation and Th2 response. We aimed to evaluate the potential pathogenic role elicited by AGEs in pediatric EoE

RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients

Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non–small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology