Usefulness of augmented reality in radiological protection education and training for interventional radiologists.

OBJECTIVE: The aim of this work is to evaluate the usefulness of using augmented reality (AR) to train medical professionals in radiological protection (RP) in fluoroscopy. METHODS: A Microsoft HoloLens 2 device has been used to simulate a fluoroscopic device. The teaching scenario considers a Philips Azurion able to rotate to pre-defined gantry positions,a dorsal decubitus patient and a ceiling shield. Radiation exposures were simulated using the FLUKA Monte Carlo code. 11 radiologists were asked to reproduce their positioning as per a clinical procedure and to correctly position the ceiling shield. Then, they were presented with the radiation exposure of their choices and were able to further optimise it. After the session, they were asked to complete a questionnaire. RESULTS: Users rated the AR educational approach as Intuitive and relevant to RP education (35%) and inspiring to deepen their knowledge (18%). Nevertheless, a negative aspect was mainly the difficulty in dealing with the system (58%). Although the participants were radiologists, a minority recognised themselves as having accurate knowledge of the RP (18%), indicating a relevant knowledge gap. CONCLUSION: The usefulness of using AR in RP education for radiologists has been shown. The visual aid of such technology is likely to improve the consolidation of practical knowledge. ADVANCES IN KNOWLEDGE: The use of interactive teaching techniques has the possibility to both help radiology professionals consolidate their radiation protection training and confidence in their practices.

A chemically defined biomimetic surface for enhanced isolation efficiency of high-quality human mesenchymal stromal cells under xenogeneic/serum-free conditions.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are one of the most frequently used cell types in regenerative medicine and cell therapy. Generating sufficient cell numbers for MSC-based therapies is constrained by (i) their low abundance in tissues of origin, which imposes the need for significant ex vivo cell expansion; (ii) donor-specific characteristics, including MSC frequency/quality, that decline with disease state and increasing age; and (iii) cellular senescence, which is promoted by extensive cell expansion and results in decreased therapeutic functionality. The final yield of a manufacturing process is therefore primarily determined by the applied isolation procedure and its efficiency in isolating therapeutically active cells from donor tissue. To date, MSCs are predominantly isolated using media supplemented with either serum or its derivatives, which poses safety and consistency issues. METHODS: To overcome these limitations while enabling robust MSC production with constant high yield and quality, the authors developed a chemically defined biomimetic surface coating called isoMATRIX (denovoMATRIX GmbH, Dresden, Germany) and tested its performance during isolation of MSCs. RESULTS: The isoMATRIX facilitates the isolation of significantly higher numbers of MSCs in xenogeneic (xeno)/serum-free and chemically defined conditions. The isolated cells display a smaller cell size and higher proliferation rate than those derived from a serum-containing isolation procedure and a strong immunomodulatory capacity. The high proliferation rates can be maintained up to 5 passages after isolation and cells even benefit from a switch towards a proliferation-specific MSC matrix (myMATRIX MSC) (denovoMATRIX GmbH, Dresden, Germany). CONCLUSION: In sum, isoMATRIX promotes enhanced xeno/serum-free and chemically defined isolation of human MSCs and supports consistent and reliable cell performance for improved stem cell-based therapies.

A Novel Synthetic, Xeno-Free Biomimetic Surface for Serum-Free Expansion of Human Mesenchymal Stromal Cells.

Human mesenchymal stromal cells (hMSCs) have enormous potential for the treatment of various inflammatory and degenerative diseases. Their manufacturing for cell-based therapies requires extensive ex vivo expansion and optimal growth conditions. To support cell adhesion, spreading, and growth in serum-free culture conditions, the applied plasticware needs to be functionalized with essential biochemical cues. By employing a recently developed screening tool, a chemically defined functional matrix composed of dextran sulfate and a bone-related extracellular matrix peptide is identified, which supports long-term culture of bone marrow-derived hMSCs in serum-free culture conditions. Cells grown under these conditions display rapid proliferation and high viability while maintaining their differentiation and immunomodulatory capacity, characteristic cell morphology, expression of hMSC-specific surface antigens as well as important markers of stemness and differentiation potential. The chemically defined, serum-free culture environment enables reliable and reproducible expansion of hMSCs important for cell based-therapies, drug screening, and disease modeling.

A Geospatial Analysis of Access to Ethnic Food Retailers in Two Michigan Cities: Investigating the Importance of Outlet Type within Active Travel Neighborhoods.

To date, the research that examines food accessibility has tended to ignore ethnic food outlets. This void leaves us with a limited understanding of how such food stores may, or may not, impact food security. The study discussed herein addressed this by conducting a geospatial assessment of ethnic food outlet accessibility in two U.S. cities: Flint and Grand Rapids, Michigan. We used Geographic Information Systems (GIS) tools to create a revealed accessibility index for each food outlet, and used the index to determine access within active travel service areas. We utilized an ordinary least squares regression (OLS), and two local models: spatial autoregression (SAR) and geographically weighted regression (GWR) to enhance our understanding of global and localized relationships between outlet accessibility and type (while controlling for known covariates). The results show that the local models outperformed (R2 max = 0.938) the OLS model. The study found that there was reduced access to ethnic restaurants in all service areas of Grand Rapids. However, in Flint, we observed this association in the bicycling areas only. Also notable were the influences that demographic characteristics had on access in each city. Ultimately, the findings tell us that nuanced planning and policy approaches are needed in order to promote greater access to ethnic food outlets and reduce overall food insecurity.

Coacervation-Mediated Combinatorial Synthesis of Biomatrices for Stem Cell Culture and Directed Differentiation.

Combinatorial screening represents a promising strategy to discover biomaterials for tailored cell culture applications. Although libraries incorporating different biochemical cues have been investigated, few simultaneously recapitulate relevant biochemical, physical, and dynamic features of the extracellular matrix (ECM). Here, a noncovalent system based on liquid-liquid phase separation (coacervation) and gelation mediated by glycosaminoglycan (GAG)-peptide interactions is reported. Multiple biomaterial libraries are generated using combinations of sulfated glycosaminoglycans and poly(ethylene glycol)-conjugated peptides. Screening these biomaterials reveals preferred biomatrices for the attachment of six cell types, including primary mesenchymal stromal cells (MSCs) and primary neural precursor cells (NPCs). Incorporation of GAGs sustains the expansion of all tested cell types comparable to standard cell culture surfaces, while osteogenic differentiation of MSC and neuronal differentiation of NPC are promoted on chondroitin and heparan biomatrices, respectively. The presented noncovalent system provides a powerful tool for developing tissue-specific ECM mimics.

Photopatterning of multifunctional hydrogels to direct adult neural precursor cells.

Matrix-metalloproteinase and photosensitive peptide units are combined with heparin and poly(ethylene glycol) into a light-sensitive multicomponent hydrogel material. Localized degradation of the hydrogel matrix allows the creation of defined spatial constraints and adhesive patterning for cells grown in culture. Using this matrix system, it is demonstrated that the degree of confinement determines the fate of neural precursor cells in vitro.

Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus.

Adult neurogenesis, the lifelong production of new neurons in the adult brain, is under complex genetic control but many of the genes involved remain to be identified. In this study, we have integrated publicly available gene expression data from the BXD and CXB recombinant inbred mouse lines to discover genes co-expressed in the adult hippocampus with Nestin, a common marker of the neural precursor cell population. In addition, we incorporated spatial expression information to restrict candidates to genes with high differential gene expression in the hippocampal dentate gyrus. Incorporating data from curated protein-protein interaction databases revealed interactions between our candidate genes and those already known to be involved in adult neurogenesis. Enrichment analysis suggested a link to the Wnt/ß-catenin pathway, known to be involved in adult neurogenesis. In particular, our candidates were enriched in targets of Lef1, a modulator of the Wnt pathway. In conclusion, our combination of bioinformatics approaches identified six novel candidate genes involved in adult neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. Further, we propose a role for Lef1 transcriptional control in the regulation of adult hippocampal precursor cell proliferation.

A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB). Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol. CONCLUSIONS/SIGNIFICANCE: The current work presents the characterization and trafficking behavior of a novel sphingolipid-binding fluorescent probe, the SBD peptide. We show that SBD binding to membranes is dependent on the presence of cholesterol, sphingomyelin, and complex glycolipids. In addition, SBD targeting through the endolysosomal pathway in neurons is highly sensitive to cholesterol perturbations, making it a potentially useful tool for the analysis of sphingolipid trafficking in disease models that involve changes in cholesterol metabolism and storage.

Interrater reliability and coding guide for nonpsychotic formal thought disorder.

Reliable and valid assessment of abnormal speech patterns may enable earlier recognition of nonpsychotic disorders through characteristic speech patterns. This study sought to establish interrater reliability using a standardized guide for scoring. A scoring guide defining 27 elements (e.g., inappropriate self-reference, simple loss of goal, circumstantiality) of disordered thought was developed. The seminal work of Andreasen's and Holzman's groups provided 12 elements, and 15 new elements were suggested by clinical literature. Audiotaped interviews with 12 psychiatric inpatients, adults of both sexes and various ages hospitalized for acute management of nonpsychotic psychiatric disorders, provided speech samples for observation of disordered thought by two independent raters. Using the guide's definitions and accompanying examples of elements of disordered thought, reliability in scoring was high (kappa of .85 for agreement on the presence of any abnormal speech element and kappa values from .66 to 1.00 for agreement on the presence of individual elements).

What does the Keane PTSD scale of the MMPI measure? Repeated measurements in a group of patients with major depression.

We looked at a group of depressed patients in a treatment study, none of whom by study design had Posttraumatic Stress Disorder (PTSD). High scores on the PTSD (PK) scale could only be due to factors other than PTSD. Despite the absence of PTSD, we observed an extremely high false positive rate in a group given the MMPI on multiple occasions. 92% of the subjects had at least one T score at or above 65 on the PK scale. 44% of the men and the women had at least one score at or above the more conservative cutoff (a raw score of 28) recommended by Lyons and Keane. The PK scale is sensitive to depression as well as anxiety and PTSD. The PK scale showed multiple high correlations with clinical and validity scales. It was concluded, in agreement with Miller, Goldberg, and Streiner (1995) and Moody and Kish (1989), that the PK scale is primarily a measure of general dysphoria. In populations with considerable psychopathology, the PK scale does not appear to discriminate between patients with and without PTSD.

Relative effects of nutrient enrichment and grazing on epiphyte-macrophyte (Zostera marina L.) dynamics.

The independent and interactive effects of nutrient concentration and epiphyte grazers on epiphyte biomass and macrophyte growth and production were examined in Zostera marina L. (eelgrass) microcosms. Experiments were conducted during early summer, late summer, fall, and spring in a greenhouse on the York River estuary of Chesapeake Bay. Nutrient treatments consisted of ambient or enriched (3× ambient) concentrations of inorganic nitrogen (ammonium nitrate) and phosphate. Grazer treatments consisted of the presence or absence of field densities of isopods, amphipods, and gastropods. epiphyte biomass increased with both grazer removal and nutrient enrichment during summer and spring experiments. The effect of grazers was stronger than that of nutrients. There was little epiphyte response to treatment during the fall, a result possibly of high ambient nutrient concentrations and low grazing pressure. Under low grazer densities of early summer, macrophyte production (g m-2 d-1) was reduced by grazer removal and nutrient enrichment independently. Under high grazer densities of late summer, macrophyte production was reduced by enrichment only with grazers absent. During spring and fall there were no macrophyte responses to treatment. The relative influence of epiphytes on macrophyte production may have been related to seasonally changing water temperature and macrophyte requirements for light and inorganic carbon.

Concurrent and Close Temporal Administration of Lithium and ECT.

The clinical effects of concurrent and close temporal administration of electroconvulsive therapy (ECT) and lithium (Li) were investigated by chart review. Three groups of patients were compared on the basis of ECT-related complications, total length of hospital stay (LOS), and post-ECT hospital stay. The groups consisted of patients administered concurrent ECT and Li (n = 27); patients administered Li within 24 h prior to ECT or within 48 h post-ECT (n = 49); and patients administered ECT without concurrent or close temporal administration of Li (n = 100). Prolonged or severe post-ECT confusion was significantly associated with close timing of administration of Li relative to the ECT course. The groups did not differ in the number of complications or the total LOS, although the post-ECT LOS was significantly longer in the group administered Li in close temporal association with ECT. These data suggest that caution should be exercised in the combined use of these treatment modalities.