Medical Extended Reality (MXR), encompassing augmented reality (AR), virtual reality (VR), and mixed reality (MR), presents a novel paradigm in radiology training by offering immersive, interactive, and realistic learning experiences in healthcare. While traditional educational tools in the field of radiology are essential, it is necessary to capitalize on the innovative and emerging educational applications of XR technologies. At the most basic level of learning anatomy, XR has been extensively utilized with an emphasis on its superiority over conventional learning methods, especially in spatial understanding and recall. For imaging interpretation, XR has fostered the concepts of virtual reading rooms by enabling collaborative learning environments and enhancing image analysis and understanding. Moreover, image-guided interventions in interventional radiology have witnessed an uptick in XR utilization, illustrating its effectiveness in procedural training and skill acquisition for medical students and residents in a safe and risk-free environment. However, there remain several challenges and limitations for XR in radiology education, including technological, economic, ergonomic, and integration into existing curricula. This review explores the transformative potential of MXR in radiology education and training along with insights on the future of XR in radiology education, forecasting advancements in immersive simulations, AI integration for personalized learning, and the potential of cloud-based XR platforms for remote and collaborative training. In summation, MXR\'s burgeoning role in reshaping radiology education offers a safer, scalable, and more efficient training model that aligns with the dynamic healthcare landscape.

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work, we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2 on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here, we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation-incompetent T362A, or the phosphorylation-mimicking T362E variants in this loop had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.

Human activities such as agriculture and urbanization generate a large number of substances like personal care products, pharmaceutical compounds, and pesticides, which often reach aquatic environments and represent a threat to biodiversity. Many organisms have developed different evolutionary strategies to remove pervasive substances from their bodies, allowing them to persist even in polluted environments, and one of these is the multixenobiotic resistance (MXR) mechanism associated with the expression of membrane proteins like P-glycoprotein (P-gp). Numerous chemical compounds with diverse functions and structures can modulate this mechanism, which can be employed as a pollution biomarker. We examined the MXR activity in two species of snails that inhabit Patagonian freshwaters. Functional assay measurements of MXR were conducted on the native Chilina dombeiana and the exotic Physella acuta in stream reaches affected by anthropogenic impacts. Results indicated that at agricultural sites, C. dombeiana snails had a more active MXR system than organisms sampled at reference and moderately disturbed urban sites, whereas P. acuta snails from agricultural and highly disturbed urban sites showed better detoxifying activity than organisms from reference sites. Only in exotic snails, part of this activity was due to the action of P-gp. The most important environmental variables explaining MXR activity were ammonium, nitrate and nitrite, phosphates, and electrical conductivity. These results show the promise of measuring MXR activity in native and exotic snails, as a biomarker in the environmental monitoring of Patagonian freshwaters.

The mussel Mytilus galloprovincialis is one of the most important aquaculture species in Europe. Its main production problem is the accumulation of toxins during coastal blooms, which prevents mussel commercialization. P-glycoprotein (ABCB1/MDR1/P-gp) is part of the multixenobiotic resistance system in aquatic organisms, and okadaic acid, the main DSP toxin, is probably a substrate of the P-gp-mediated efflux. In this study, the presence and possible role of P-gp in the okadaic acid detoxification process was studied in M. galloprovincialis. We identified, cloned, and characterized two complete cDNAs of mdr1 and mdr2 genes. MgMDR1 and MgMDR2 predicted proteins had the structure organization of ABCB full transporters, and were identified as P-gp/MDR/ABCB proteins. Furthermore, the expression of mdr genes was monitored in gills, digestive gland, and mantle during a cycle of accumulation-elimination of okadaic acid. Mdr1 significantly increased its expression in the digestive gland and gills, supporting the idea of an important role of the MDR1 protein in okadaic acid efflux out of cells in these tissues. The expression of M. galloprovincialismrp2, a multidrug associated protein (MRP/ABCC), was also monitored. As in the case of mdr1, there was a significant induction in the expression of mrp2 in the digestive gland, as the content of okadaic acid increased. Thus, P-gp and MRP might constitute a functional defense network against xenobiotics, and might be involved in the resistance mechanisms to DSP toxins.

Neonicotinoids are the most widely used synthetic insecticides in the world. These insecticides are widely distributed in the ecosystem, indicating that more attention should be paid to the potential risks regarding their use in agriculture. Due their intensive use, non-target species in the environment are also exposed to their putative effects. Within acute exposure trials, the time related effect of sublethal dose of the neonicotinoid preparation APACS 50 WG was investigated on swimming behaviour and the multi-xenobiotic resistance system (MXR) activity, as a first line defence pathway of adult Dikerogammarus villosus. Results showed that treated animals manifested an increased swimming activity. Exposed animals were monitored by the rhodamine B accumulation assay, and APACS 50 WG exerted distinct changes in the MXR activity as well. Our results suggested that application of neonicotinoid at a low concentration (3.9 ng/l) contributed to the activation of locomotor activity and at the same concentration range the transmembrane transport mechanisms was altered too.

ATP-binding cassette (ABC) efflux pumps mediate the activity of the Multixenobiotic Resistance (MXR) mechanism and have been proposed as a biomarker of environmental pollution mainly in aquatic invertebrates. MXR activity was never investigated in Collembola and represents a potential tool for soil biomonitoring. This study aimed to characterize for the first time the activity of ABC efflux pumps in the gut of collembolan species, and investigate its responsiveness to cadmium (Cd), a common stressor found in polluted soils. We performed in vitro rhodamine-B accumulation assays in the presence of model inhibitors of ABC efflux pumps: verapamil hydrochloride as P-gp (P-glycoprotein) inhibitor, and MK571, as MRPs (multidrug resistance-related proteins) inhibitor. We also performed rhodamine-B accumulation assays under Cd-exposure (209 μg/L;1 μM). Our results showed that all species presented basal (noninduced) level of MXR activity in their gut. Efflux pumps P-gp and/or MRPs activity were confirmed in Cyphoderus innominatus, Cyphoderus similis, and Folsomia candida, the standard species. The rhodamine-B accumulation assays performed with Cd, applied as soil pollutant, showed that the gut of non-standard species C. similis and Trogolaphysa sp. presented an increase of MXR activity for both P-gp and MRP transporters, indicating the potential of these species as test organisms for soil ecotoxicology studies in Neotropical region. Our findings suggest a functional role of ABC transporters in the collembolan gut and their cellular involvement in Cd defense response, corroborating that MXR phenotype in Collembola can be a promising tool for bioindication of soil contamination.

Cristina N. Horak and Yanina A. Assef (2017) P-glycoprotein (P-gp) mediated multixenobiotic resistance (MXR) is a mechanism analogous to multidrug resistance, which has been extensively characterized in mammalian tumours. The expression and function of the MXR mechanism has been demonstrated in numerous aquatic organisms and has been proposed as a biomarker for pollution assessment. A close relationship between thermal stress and MXR response has been reported in some aquatic organisms. Seasonal studies in freshwater organisms are scarce and conducted mainly in zebra mussel (Dreissena polymorpha), whose presence has not been reported in South America. The general purpose of the present study was to evaluate seasonal variation of a biomarker, the MXR mechanism, in the worldwide distributed freshwater snail P. acuta. We analyzed the in situ influence of temperature on the biomarker response over an 18-month field study. MXR defence system was evaluated by a combination of functional assays (RB accumulation) and molecular approaches to analyse P-gp expression. The results demonstrated a linear correlation between MXR response, at activity and expression level, and water temperature at sample site, in P. acuta snails. The characterization of the MXR system in worldwide distributed species, including the study of their seasonal fluctuations, could contribute to the increasing interest to incorporate this biomarker to provide an integrated assessment of mussel health status. This work supports the possible use of P. acuta snails with this purpose and also highlights that the occurrence of variations in MXR response related to water temperature has to be taken into account in the interpretation of in situ monitoring studies.

We investigated the activity of the multixenobiotic resistance (MXR) phenotype, a biological defense system in aquatic organisms, in the fish assemblages of two tropical estuaries with different degrees of environmental impacts, the Paraiba River and Mamanguape River Estuaries. The aim of this work was to compare the activity of the MXR phenotype of different fishes to test the hypothesis that each species has an inherent activity level and to use this activity as a bioindicator of aquatic contamination. We assessed the MXR activity of the gills, using rhodamine B (RB) accumulation assay. The results demonstrated a species-specific difference in the MXR activity of fishes caught in the same estuarine zone. Also, the pelagic species Eucinostomus melanopterus, Eucinostomus argenteus, and Lutjanus jocu had higher RB accumulation, while the demersal species Sphoeroides testudineus and Sphoeroides greeleyi had the lowest RB accumulation, suggesting that the ecological characteristic of fish in the water column exerts an influence on MXR activity. Besides, we demonstrated the potential of using the gill MXR activity of the key estuarine species, the Brazilian silversides Atherinella brasiliensis, as a tool for biomonitoring estuaries.

The literature indicates that exotic species have a greater tolerance to environmental stressors compared with native species. In recent decades, the introduction of contaminants into the environment has increased as a result of industrialization. The objective of this study was to verify the resistance of bivalve mollusks from freshwater native (Anodontites trapesialis) and exotic (Limnoperna fortunei) species to chemical contamination using an ex vivo/in vitro approach. Gill and muscle tissues were exposed to two different types of environmental stressors, copper (metal), and Roundup Transorb® (herbicide). The tissues were submitted to a cytotoxicity test in which the lysosomal integrity was assessed, from the adaptation of a method to isolated cells, and multixenobiotic resistance (MXR) test which evaluated cellular defense. In the exotic species, only copper at 9000 μg/L and Roundup Transorb® at 5000 μg/L were cytotoxic. In the native species, copper cytotoxicity at 900 and 9000 μg/L and Roundup Transorb® at 50 and 5000 μg/L were observed. Results were the same in both tissues. The MXR, responsible for the extrusion of contaminants (cell defense), was inhibited in both species when exposed to the contaminants, this cell defense system seems to be more inhibited in the native species, when exposed to both pollutants, indicating greater sensitivity. Therefore, cytotoxicity may be related to the lack of capacity of cellular defense. In relation to lysosomal integrity, the native species was more sensitive to cytotoxic pollutants, where a greater number of experimental conditions of metals and herbicide showed cytotoxicity, as well as more experimental situations inhibited its ability to defend itself.

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics; thus the relatively frequent polymorphic and mutant ABCG2 variants in the population may significantly alter disease conditions and pharmacological effects. Low-level or non-functional ABCG2 expression may increase individual drug toxicity, reduce cancer drug resistance, and result in hyperuricemia and gout. In the present work we have studied the cellular expression, trafficking, and function of nine naturally occurring polymorphic and mutant variants of ABCG2. A comprehensive analysis of the membrane localization, transport, and ATPase activity, as well as retention and degradation in intracellular compartments was performed. Among the examined variants, R147W and R383C showed expression and/or protein folding defects, indicating that they could indeed contribute to ABCG2 functional deficiency. These studies and the applied methods should significantly promote the exploration of the medical effects of these personal variants, promote potential therapies, and help to elucidate the specific role of the affected regions in the folding and function of the ABCG2 protein.