Standardizing Behavioral Health Triage: Using the HEADS-ED Tool

Background: In the past two years emergency departments across the country have experienced an increase in pediatric patients requiring behavioral health care. It is essential to provide efficient, early intervention to these vulnerable patients. The use of a standardized tool can improve management of pediatric patients and allow access to resources in a timely manner. Purpose: To evaluate the implementation of the HEADS-ED in a community hospital ED, to provide rapid behavioral health assessment. Methods: Education for staff was provided through various platforms and involved regular support for staff throughout the intervention. It was hypothesized that implementation of this tool would improve efficiency and ability to manage behavioral health patient needs and decrease the behavioral health length of stay. Results: While the length of stay decrease did not meet the project goal of 25%, there was a 15% decrease in the median length of stay. The screen was completed on 77 patients, 20.31% of all behavioral health patients and 1.97% of all pediatric ED patients, from age four to twenty. Of the patients screened, 61 patients or 79.2% screened were provided with a recommended resource. There was positive response from staff and there were found to be multiple statistically significant relationships between multiple different variables assessed with the HEADS-ED tool, highlighting areas for future study. Conclusion: This project outlines the steps required to implement a standardized tool for ED behavioral health triage, which staff reported as a positive intervention to provide rapid assessment and disposition planning

β-Catenin is a pH sensor with decreased stability at higher intracellular pH.

β-Catenin functions as an adherens junction protein for cell-cell adhesion and as a signaling protein. β-catenin function is dependent on its stability, which is regulated by protein-protein interactions that stabilize β-catenin or target it for proteasome-mediated degradation. In this study, we show that β-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster β-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase β-TrCP. While β-catenin phosphorylation was pH independent, higher pHi induced increased β-TrCP binding and decreased β-catenin stability. An evolutionarily conserved histidine in β-catenin (found in the β-TrCP DSGIHS destruction motif) is required for pH-dependent binding to β-TrCP. Expressing a cancer-associated H36R-β-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic β-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of β-catenin stability, functioning in coincidence with phosphorylation

extradenticle determines segmental identities throughout Drosophila development

extradenticle (exd) and the homeotic selector proteins together establish segmental identities by coordinately regulating the expression of downstream target genes. The inappropriate expression of these targets in exd mutant embryos results in homeotic transformations and aberrant morphogenesis. Here we examine the role of exd in adult development by using genetic mosaics and a hypomorphic exd allele caused by a point mutation in the homeodomain. exd continues to be essential for the specification of segmental identities, consistent with a continuing requirement for exd as cofactor of the homeotic selector proteins. Loss of exd results in the homeotic transformation of abdominal segments to an A5 or A6 segmental identity, the antenna and arista to leg, and the head capsule to dorsal thorax or notum. Proximal leg structures are particularly sensitive to the loss of exd, although exd does not affect the allocation of proximal positional values of the leg imaginal disc. Using heat-shocks to induce expression of a hsp70-exd fusion gene, we show that, in contrast to the homeotic selector genes, ubiquitously high levels of exd expression do not cause pattern abnormalities or segmental transformations

Regulation of Epithelial Morphogenesis by the G Protein-Coupled Receptor Mist and Its Ligand Fog

Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes

Rab11 Helps Maintain Apical Crumbs and Adherens Junctions in the Drosophila Embryonic Ectoderm

BackgroundTissue morphogenesis and organogenesis require that cells retain stable cell-cell adhesion while changing shape and moving. One mechanism to accommodate this plasticity in cell adhesion involves regulated trafficking of junctional proteins.Methodology/Principal FindingsHere we explored trafficking of junctional proteins in two well-characterized model epithelia, the Drosophila embryonic ectoderm and amnioserosa. We find that DE-cadherin, the transmembrane protein of adherens junctions, is actively trafficked through putative vesicles, and appears to travel through both Rab5-positive and Rab11-positive structures. We manipulated the functions of Rab11 and Rab5 to examine the effects on junctional stability and morphogenesis. Reducing Rab11 function, either using a dominant negative construct or loss of function alleles, disrupts integrity of the ectoderm and leads to loss of adherens junctions. Strikingly, the apical junctional regulator Crumbs is lost before AJs are destabilized, while the basolateral protein Dlg remains cortical. Altering Rab5 function had less dramatic effects, not disrupting adherens junction integrity but affecting dorsal closure.Conclusions/SignificanceWe contrast our results with what others saw when disrupting other trafficking regulators, and when disrupting Rab function in other tissues; together these data suggest distinct mechanisms regulate junctional stability and plasticity in different tissues

Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia

Hydrothermal interaction of solid wafers of Topopah Spring Tuff with J-13 water and distilled water at 90, 150, and 250{sup 0}C, using Dickson-type, gold-bag rocking autoclaves

The Nevada Nuclear Waste Storage Investigations Project has conducted experiments to study the hydrothermal interaction of rock and water representative of a potential high-level waste repository at Yucca Mountain, Nevada. The results of these experiments help define the near-field repository environment during and shortly after the thermal period that results from the emplacement of nuclear waste. When considered in conjunction with results contained in companion reports, these results can be used to assess our ability to accelerate tests using the surface area/volume parameter and/or temperature. These rock-water interaction experiments were conducted with solid polished wafers cut from both drillcore and outcrop samples of Topopah tuff, using both a natural ground water and distilled water as the reacting fluid. Pre- and post-test characterization of the reacting materials was extensive. Post-test identification and chemical analysis of secondary phases resulting from the hydrothermal interactions were aided by using monoliths of tuff rather than crushed material. All experiments were run in Dickson-type, gold-bag rocking autoclaves that were periodically sampled at in situ conditions. A total of nine short-term (up to 66-day) experiments were run in this series; these experiments covered the range from 90 to 250{sup 0}C and from 50 to 100 bar. The results obtained from the experiments have been used to evaluate the modeled results produced by calculations using the geochemical reaction process code EQ3/6. 31 refs., 37 figs., 7 tabs

Hydrothermal Interaction of Topopah Spring Tuff With J-13 Water as a Function of Temperature

In support of the Nevada Nuclear Waste Storage Investigations Project experiments were conducted to study the hydrothermal interaction of rock and water representative of a potential repository in tuff. These experiments provided data relevant to near-field repository conditions that can be used to: assess the ability to use accelerated tests based on the SA/V (surface area/volume) parameter and temperature; allow the measurement of chemical changes in phases present in the tuff before reaction as well as the identification and chemical analysis of secondary phases resulting from hydrothermal reactions; and demonstrate the usefulness of geochemical modeling in a repository environment using the EQ3/6 thermodynamic/kinetic geochemical modeling code. Crushed tuff and polished wafers of tuff were reacted with a natural ground water in Dickson-type gold-cell rocking autoclaves which were periodically sampled under in-situ conditions. Results were compared with predictions based on the EQ3/6 geochemical modeling code. Eight short-term experiments (2 to 3 months) at 150{sup 0}C and 250{sup 0}C have been completed using tuff from both drillcore and outcrop. Long-term experiments at 90{sup 0}C and 150{sup 0}C using drillcore polished wafers are in progress. This paper will focus on the results of the 150{sup 0}C and 250{sup 0}C experiments using drill core polished wafers. 11 references, 4 figures

Analysis of Compound Synergy in High-Throughput Cellular Screens by Population-Based Lifetime Modeling

Despite the successful introduction of potent anti-cancer therapeutics, most of these drugs lead to only modest tumor-shrinkage or transient responses, followed by re-growth of tumors. Combining different compounds has resulted in enhanced tumor control and prolonged survival. However, methods querying the efficacy of such combinations have been hampered by limited scalability, analytical resolution, statistical feasibility, or a combination thereof. We have developed a theoretical framework modeling cellular viability as a stochastic lifetime process to determine synergistic compound combinations from high-throughput cellular screens. We apply our method to data derived from chemical perturbations of 65 cancer cell lines with two inhibitors. Our analysis revealed synergy for the combination of both compounds in subsets of cell lines. By contrast, in cell lines in which inhibition of one of both targets was sufficient to induce cell death, no synergy was detected, compatible with the topology of the oncogenically activated signaling network. In summary, we provide a tool for the measurement of synergy strength for combination perturbation experiments that might help define pathway topologies and direct clinical trials