Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction

Pandemic Preparedness and Response in the Age of Technology

The Fourth Annual White Paper from the Scowcroft Institute of International Affairs at The Bush School of Government & Public Service at Texas A&M UniversityEffective pandemic preparedness and response depend on the quality as well as the speed of obtaining relevant information, especially from remote and hard to reach areas of the world, where most known and unknown disease outbreaks occur and originate. Equally important is the local/national ability to collate, analyze, and interpret the information in a form valuable for taking appropriate preventive action and response. For web-based surveillance systems to be more effective, it is important that the capacity to collate, analyze, interpret, and disseminate the information in a form that results in appropriate preventive action and response in the countries where these diseases originate. The COVID-19 pandemic has demonstrated the ability to obtain information from different sources and dissemination of such information globally. Despite the availability of information on the development of the pandemic from a Public Health Emergency of International Concern (PHEIC), many countries were unprepared when the pandemic finally reached their borders. It is not enough for countries to efficiently analyze disease surveillance data, they must actively prepare to prevent the entry of a disease into their territory and, at the same time, prepare plans and identify and initiate containment measures that need to be taken to prevent the establishment of the disease in the country

Global leadership at the crossroads: Are we prepared for the next pandemic?

"In this report, the Scowcroft Institute of International Affairs at The Bush School of Government & Public Service at Texas A&M University outlines eight priority areas and their accompanying recommended action items to address vulnerabilities in the current pandemic preparedness and response system. Collectively, they represent issues the international community should address in order to establish pandemic preparedness and response capabilities." -- p. 5

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Optimal postnodal lymphatic network structure that maximizes active propulsion of lymph

The lymphatic system acts to return lower-pressured interstitial fluid to the higher-pressured veins by a complex network of vessels spanning more than three orders of magnitude in size. Lymphatic vessels consist of lymphangions, segments of vessels between two unidirectional valves, which contain smooth muscle that cyclically pumps lymph against a pressure gradient. Whereas the principles governing the optimal structure of arterial networks have been identified by variations of Murray's law, the principles governing the optimal structure of the lymphatic system have yet to be elucidated, although lymph flow can be identified as a critical parameter. The reason for this deficiency can be identified. Until recently, there has been no algebraic formula, such as Poiseuille's law, that relates lymphangion structure to its function. We therefore employed a recently developed mathematical model, based on the time-varying elastance model conventionally used to describe ventricular function, that was validated by data collected from postnodal bovine mesenteric lymphangions. From this lymphangion model, we developed a model to determine the structure of a lymphatic network that optimizes lymph flow. The model predicted that there is a lymphangion length that optimizes lymph flow and that symmetrical networks optimize lymph flow when the lymphangions downstream of a bifurcation are 1.26 times the length of the lymphangions immediately upstream. Measured lymphangion lengths (1.14 ± 0.5 cm, n = 74) were consistent with the range of predicted optimal lengths (0.1–2.1 cm). This modeling approach was possible, because it allowed a structural parameter, such as length, to be treated as a variable