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It is currently impossible to perform an evidence-based risk assessment for medication use during breastfeeding. The ConcePTION project aims to provide information about the use of medicines during lactation. The study aimed to develop and characterize an in vitro model of the blood–milk barrier to determine the extent of the milk transfer of xenobiotics, relying on either on human mammary epithelial cells (hMECs) or immortalized cell lines derived from breast tissue. The hMECs were cultured and characterized for epithelial markers; further, the ability to form an epithelial barrier was investigated. Drug transporter functionality in the cultured hMECs was analyzed with specific probe substrates. The hMECs showed an epithelial morphology and the expression of epithelial markers and tight junctions. They formed a reproducible tight barrier with a transepithelial electrical resistance greater than 400 Ωcm2, unlike immortalized cell lines. Different levels of mRNA expression were detected for 81 genes of membrane transporters. Functional assays showed no evidence for the transporter-mediated secretion of medicines across the hMECs. Nevertheless, the hMEC-based in vitro model covered a 50-fold range of permeability values, differentiating between passive transcellular and paracellular-mediated transport. The cultured hMECs proved to be a promising in vitro model for biorelevance; the wide characterization of hMECs makes them useful for studying medicine partitioning in milk. [ABSTRACT FROM AUTHOR]

Aim: The osteogenic potential of new premixed calcium‐silicate‐containing bioceramic sealers (Ca‐Si sealers) was tested with porcine vascular wall‐mesenchymal stem cells (pVW‐MSCs). Methodology: Two Ca‐Si‐containing sealers: Ceraseal (MetaBiomed, Cheong‐si, South Korea) and AH Plus Bioceramic (Maruchi, Wonju‐si, South Korea), and an epoxy resin sealer (AH Plus; Dentsply, Konstanz, Germany) as a control, were prepared according to the manufacturers' indications. All samples were allowed to set for 100% of their setting time in a sterile humid cabinet at 37°C and 95% relative humidity. pVW‐MSC seeding efficiency and osteogenic differentiation were analysed as marker of gene/protein expression for up to 12 days. Mineralization assay and immunofluorescence staining were performed and evaluated over a period of 21 days. Statistical analyses were conducted using one‐way analysis of variance (p <.05). Additional samples were prepared and stored under the same conditions and inspected using an environmental scanning electron microscope equipped with an energy dispersive X‐ray spectroscopy system. Results: Significantly higher cell seeding efficiency (p <.05) was observed for both Ca‐Si sealers from day 8. pVW‐MSCs showed a significant shift towards the osteogenic lineage only when seeded in contact with Ca‐Si sealers. Gene expression of osteopontin was upregulated significantly. Collagen I and osteocalcin were clearly expressed by cells in contact with Ca‐Si sealers. Mineralization granules were observed in Alizarin red assays and confocal laser scanning microscopy analysis of both Ca‐Si sealers. No gene expression or granule mineralization were observed on the epoxy resin sealer. Conclusions: Premixed Ca‐Si sealers displayed a higher potential for osteogenic activity on pVW‐MSCs. Epoxy resin sealer was unable to induce any osteogenic activity. The properties of both Ca‐Si sealers suggest their potential as osteoinductive platforms for vascular MSCs in periapical bone. [ABSTRACT FROM AUTHOR]

There is a lack of operable methods, criteria and tools that enable public authorities to purchase goods, services and works that contribute to both climate change mitigation and adaptation. Based on our experience as coordinators of 8 public procurement procedures within an ongoing Horizon Europe project, we suggest a new approach to climate proofing of public procurement, identify urgent research developments and recommend the amendment of public procurement policies to incorporate new criteria. [ABSTRACT FROM AUTHOR]

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We consider the following prescribed Q -curvature problem: Δ 2 u = (1 − | x | p) e 4 u on  ℝ 4 , Λ : = ∫ ℝ 4 (1 − | x | p) e 4 u d x  <  ∞. (1) We show that for every polynomial P of degree 2 such that lim | x | → + ∞ P = − ∞ , and for every Λ ∈ (0 , Λ s p h) , there exists at least one solution to problem  (1) which assumes the form u = w + P , where w behaves logarithmically at infinity. Conversely, we prove that all solutions to  (1) have the form v + P , where v (x) = 1 8 π 2 ∫ ℝ 4 log | y | | x − y | (1 − | y | p) e 4 u d y and P is a polynomial of degree at most two bounded from above. Moreover, if u is a solution to  (1), it has the following asymptotic behavior: u (x) = − Λ 8 π 2 log | x | + P + o (log | x |) , as  | x | → + ∞. As a consequence, we give a geometric characterization of solutions in terms of the scalar curvature at infinity of the associated conformal metric e 2 u | d x | 2 . [ABSTRACT FROM AUTHOR]