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In the present study, a customized device (Epi-ExPer) was designed and fabricated to facilitate an epithelial organ culture, allowing for controlled exposure to exogenous chemical stimuli and accommodating the evaluation of permeation of the tissue after treatment. The Epi-ExPer system was fabricated using a stereolithography (SLA)-based additive manufacturing (AM) method. Human and porcine oral epithelial mucosa tissues were inserted into the device and exposed to resinous monomers commonly released by dental restorative materials. The effect of these xenobiotics on the morphology, viability, permeability, and expression of relevant markers of the oral epithelium was evaluated. Tissue culture could be performed with the desired orientation of air-liquid interface (ALI) conditions, and exposure to xenobiotics was undertaken in a spatially guarded and reproducible manner. Among the selected monomers, HEMA and TEGDMA reduced tissue viability at high concentrations, while tissue permeability was increased by the latter. Xenobiotics affected the histological image by introducing the vacuolar degeneration of epithelial cells and increasing the expression of panCytokeratin (pCK). Epi-ExPer device offers a simple, precise, and reproducible study system to evaluate interactions of oral mucosa with external stimuli, providing a biocompatibility and permeability assessment tool aiming to an enhanced in vitro/ex vivo-to-in vivo extrapolation (IVIVE) that complies with European Union (EU) and Food and Durg Administration (FDI) policies. [ABSTRACT FROM AUTHOR]

Placental structure is linked to function across morphological scales. In the placenta, changes to gross anatomy, such as surface area, volume, or blood vessel arrangement, are associated with suboptimal physiological outcomes. However, quantifying each of these metrics requires different laborious semi-quantitative methods. Here, we demonstrate how, with minimal sample preparation, whole-organ computed microtomography (microCT) can be used to calculate gross morphometry of the equine placenta and a range of additional metrics, including branching morphometry of placental vasculature, non-destructively from a single dataset. Our approach can be applied to quantify the gross structure of any large mammalian placenta. • Using a walk-in microCT system, we quantitatively imaged a whole equine placenta. • From our microCT dataset, we could quantify key anatomical metrics. • Our approach is transferrable to quantifying any large mammalian placenta. [ABSTRACT FROM AUTHOR]

Thalattosuchian crocodylomorphs were a ubiquitous component of shallow marine ecosystems during the Jurassic and Early Cretaceous. Alas, their origins remain a mystery. Here we describe three specimens from the Sinemurian (and possibly Early Pliensbachian) of the UK: a partial cranial rostrum, a series of cervical vertebrae, and two dorsal vertebrae adhered with matrix. These specimens are amongst the oldest known thalattosuchian fossils, with the partial cranial rostrum being the oldest known non-neothalattosuchian thalattosuchian. This partial cranial rostrum has a unique combination of rostral characters never seen before in any crocodylomorph, and helps to elucidate early thalattosuchian internal rostrum evolution, suggesting that the reduction in thalattosuchian paranasal sinuses was not related to either the reorganization of rostral neurovasculature seen in later diverging taxa or the increased cancellous bone microstructure. Based on our CT sample, a shift in cranial bone microstructure occurred in the Eoneustes  + Metriorhynchidae subclade, one that coincided with the enlargement of the salt glands and decoupling of the external antorbital fenestra from the paranasal sinuses. Without extensive histological sampling we cannot determine whether the shift to an obligate aquatic lifestyle occurred prior to the evolution of Metriorhynchidae. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a persistent epidemic, and the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) presents a global healthcare threat. While some new agents have been successfully introduced, innovative technologies to evaluate emerging anti-TB compounds are required to inform transformative approaches. Mtb is an obligate human pathogen, and consequently utilizing models that are consistent with human disease is likely to be critical. We have developed a human 3-dimensional (3-D) cell culture model that reflects human disease gene expression patterns and causes Mtb to become pyrazinamide sensitive in vitro. Here, we identify key differences in virulence between the standard laboratory strain, Mtb H37Rv, and clinical isolates. We demonstrate that Mtb H37Rv is attenuated in the 3-D system, more susceptible to antibiotics and hyperinflammatory compared to clinical isolates. Prolonged in vitro culture of a clinical strain leads to attenuation. We then characterise antibiotic sensitivity of multi-drug-resistant Mtb within the 3-D model and define relative bactericidal activity. Finally, we demonstrate that verapamil increases efficacy of bedaquiline and delamanid antibiotic therapy. Taken together, our findings suggest that studying virulent clinical strains in an advanced cell culture system is a powerful adjunct to established methodologies to evaluate new interventions for TB. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown. [ABSTRACT FROM AUTHOR]

Radiolabelled bisphosphonates (BPs) and [18F]NaF (18F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [18F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging. These two radiotracers bind calcium mineral deposits via different mechanisms, with BPs chelating to calcium ions and thus being non-selective, and [18F]NaF being selective for hydroxyapatite (HAp) which is the main component of bone mineral. Considering that the composition of EC has been reported to include a diverse range of non-HAp calcium minerals, we hypothesised that BPs may be more sensitive for imaging EC due to their ability to bind to both HAp and non-HAp deposits. We report a comparison between the 68Ga-labelled BP tracer [68Ga]Ga-THP-Pam and [18F]NaF for PET imaging in a rat model of EC that develops macro- and microcalcifications in several organs. Macrocalcifications were identified using preclinical computed tomography (CT) and microcalcifications were identified using µCT-based 3D X-ray histology (XRH) on isolated organs ex vivo. The morphological and mineral analysis of individual calcified deposits was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). PET imaging and ex vivo analysis results demonstrated that while both radiotracers behave similarly for bone imaging, the BP-based radiotracer [68Ga]Ga-THP-Pam was able to detect EC more sensitively in several organs in which the mineral composition departs from that of HAp. Our results strongly suggest that BP-based PET radiotracers such as [68Ga]Ga-THP-Pam may have a particular advantage for the sensitive imaging and early detection of EC by being able to detect a wider array of relevant calcium minerals in vivo than [18F]NaF, and should be evaluated clinically for this purpose. [ABSTRACT FROM AUTHOR]