A conscious mouse model of gastric ileus using clinically relevant endpoints

BACKGROUND: Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. METHODS: Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. RESULTS: Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. CONCLUSION: Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of stomach function appears to be simultaneous to colonic recovery

An inclusive Research and Education Community (iREC) model to facilitate undergraduate science education reform

Funding: This work was supported by Howard Hughes Medical Institute grants to DIH is GT12052 and MJG is GT15338.Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.Peer reviewe

Improving Stream Bank Erosion Estimates by Adjusting the Applied Shear Stress for Different Bank Characteristics

Stream bank erosion rates are commonly modeled using the excess shear stress equation εr = kd(τ-τc)a, where the exponent a is assumed to be unity. The coefficient of erodibility kd, and the critical shear stress τc [Tau c] are properties of the bank soil and the applied shear stress τ [Tau] is a function of the channel geometry and discharge. This equation appears to overstimate bank erosion likely due to effects of channel morphology and bank vegetation, among other factors. The objective of this study was to determine whether the excess shear stress equation could be parameterized with an α [alpha] coefficient to more accurately estimate stream bank erosion accounting for the effects of channel curvature and bank vegetation. The study included seven stream bank sites at Beaver, Bullrun, and Stock creeks located in Knox County, Tennessee with USGS gaging stations located downstream. Bank erosion pins were placed at four channel morphology/vegetation categories to measure retreat or soil deposition; they were straight and curved channels with and without woody bank vegetation. At each channel cross-section, 18-inch steel pins were installed vertically along the lower, middle, and upper portion of the banks. A mini-jet test device was used to approximate kd and the τc using the Blaisdell method (BM). Flows and stage heights were modeled with HEC-RAS to determine the τ at each pin. Pin erosion averages varied by category and bank position ranging from -0.03 to -0.78 feet during the one-year study period and were used as estimates of site erosion rates εr [Epsilon r]. With all the parameters being known alpha parameters in the modified excess shear stress equation were solved for each of the erosion pins for the different channel categories. The alpha values typically varied between about 0.001 and 0.73 showing that excess shear stress equation over predicts erosion. Due to the wide range of alpha values, further research is needed to better assess the factors that influence bank erosion and improve the predictability of bank retreat rates

Resource Disputes in South Asia: Water Scarcity and the Potential for Interstate Conflict

For PA 860: Workshop in International Public AffairsThis report explores the role of water shortages related to transboundary rivers in interstate disputes in South Asia. The report analyzes the history and status of disputes, looking at the relationships between India and neighboring Pakistan, Bangladesh, and Nepal. The core of the report analyzes supply and demand with projections based on the PODIUM model. Water likely will continue to be a major source of conflict, as shortages will occur in India, Bangladesh, and, especially, Pakistan

Characterizing the Influence of Print Parameters on Porosity and Resulting Density

Extrusion deposition additive manufacturing produces parts with inherent porosity, which typically manifests as easily accessible voids between beads. This open porosity can also be accompanied by voids within the beads themselves, and both types can impact a part’s desired performance. Porosity is influenced by a variety of factors, including infill percentage, layer height, nozzle diameter, print speed, and raster orientation. While their influence on mechanical properties and porosity have been studied previously, there has been minimal work connecting print parameters to porosity and subsequently to mechanical performance. This study investigates the relationships between print parameters, volumetric porosity, and mechanical performance. In addition, this study measures both open and closed porosity through use of a helium pycnometer rather than image analysis of a cross-section. Thus, this study will identify correlations between the volumetric density of parts and the resulting mechanical performance as a function of print parameters.Mechanical Engineerin

Increasing the Interlayer Bond of Fused Filament Fabrication Samples with Solid Cross-Sections using Z-Pinning

The mechanical properties of parts made by fused filament fabrication is highly anisotropic, with the strength across layers (z-axis) typically measuring ~50% lower than the strength along the direction of the extruded material (x-axis). A z-pinning method has been developed in which material is extruded in the z-direction to fill intentionally aligned voids in the x-y print pattern. In previous studies that involved a sparse rectilinear grid cross-section (35% infill), the z-pinning approach demonstrated more than a 3.5x increase in strength in the z-direction. The current study expanded these efforts to evaluate the use of z-pins in a printed sample with a solid cross-section. Although a solid cross-section is more common in structural components, it is much less forgiving of instabilities that may occur in the z-pinning approach (such as over-filling). Even though this study utilized a low pin volume (~43% fill factor), the pinning approach demonstrated a 40% increase in z-direction strength for solid samples that had similar printing times.Mechanical Engineerin

Recognition and management of perinatal depression in general practice: a survey of GPs and postnatal women

OBJECTIVE To identify ways to improve detection and access to treatment.\ud \ud METHODS A survey of general practitioners and postnatal women across Australia addressing knowledge of, and attitudes to, postnatal depression using case vignettes.\ud \ud RESULTS General practitioners were significantly more likely to recognise depression than postnatal women, who were likely to seek help for more general or baby related issues. Both GPs and women favoured help from partners and counselling, but GPs significantly favoured antidepressants and women, natural therapies.\ud \ud DISCUSSION Women have a low likelihood of presenting for depression, suggesting a role for screening by GPs. Women preferred psychological and social management than drugs for depression perinatally

Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction

© 2021 National Academy of Sciences. All rights reserved. In mammalian cells, nutrients and growth factors signal through an array of upstream proteins to regulate the mTORC1 growth control pathway. Because the full complement of these proteins has not been systematically identified, we developed a FACS-based CRISPR-Cas9 genetic screening strategy to pinpoint genes that regulate mTORC1 activity. Along with almost all known positive components of the mTORC1 pathway, we identified many genes that impact mTORC1 activity, including DCAF7, CSNK2B, SRSF2, IRS4, CCDC43, and HSD17B10. Using the genome-wide screening data, we generated a focused sublibrary containing single guide RNAs (sgRNAs) targeting hundreds of genes and carried out epistasis screens in cells lacking nutrient- and stress-responsive mTORC1 modulators, including GATOR1, AMPK, GCN2, and ATF4. From these data, we pinpointed mitochondrial function as a particularly important input into mTORC1 signaling. While it is well appreciated that mitochondria signal to mTORC1, the mechanisms are not completely clear. We find that the kinases AMPK and HRI signal, with varying kinetics, mitochondrial distress to mTORC1, and that HRI acts through the ATF4-dependent up-regulation of both Sestrin2 and Redd1. Loss of both AMPK and HRI is sufficient to render mTORC1 signaling largely resistant to mitochondrial dysfunction induced by the ATP synthase inhibitor oligomycin as well as the electron transport chain inhibitors piericidin and antimycin. Taken together, our data reveal a catalog of genes that impact the mTORC1 pathway and clarify the multifaceted ways in which mTORC1 senses mitochondrial dysfunction