Inhaled carbon monoxide protects against the development of shock and mitochondrial injury following hemorrhage and resuscitation

Aims: Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. Results: Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). Conclusion: These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted

Molecular mechanisms and cellular functions of cGAS-STING signalling

The cGAS–STING signalling axis, comprising the synthase for the second messenger cyclic GMP–AMP (cGAS) and the cyclic GMP–AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGAS–STING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGAS–STING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-κB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquid–liquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved

[Letter from H. R. Nassour to Meyer Bodansky - September 1, 1939]

Letter to Dr. Meyer Bodansky from H. R. Nassour, Jr., dated September 1, 1939. The letter thanks Dr. Bodansky for advice that he gave two years prior. Mr. Nassour updates Dr. Bodansky on his current situation in regards to his medical education, and states that he would like to visit him

Learning of Central Pattern Generator Coordination in Robot Drawing

How do robots learn to perform motor tasks in a specific condition and apply what they have learned in a new condition? This paper proposes a framework for motor coordination acquisition of a robot drawing straight lines within a part of the workspace. Then, it addresses transferring the acquired coordination into another area of the workspace while performing the same task. Motor patterns are generated by a Central Pattern Generator (CPG) model. The motor coordination for a given task is acquired by using a multi-objective optimization method that adjusts the CPGs' parameters involved in the coordination. To transfer the acquired motor coordination to the whole workspace we employed (1) a Self-Organizing Map that represents the end-effector coordination in the Cartesian space, and (2) an estimation method based on Inverse Distance Weighting that estimates the motor program parameters for each SOM neuron. After learning, the robot generalizes the acquired motor program along the SOM network. It is able therefore to draw lines from any point in the 2D workspace and with different orientations. Aside from the obvious distinctiveness of the proposed framework from those based on inverse kinematics typically leading to a point-to-point drawing, our approach also permits of transferring the motor program throughout the workspace

[Correspondence between Meyer Bodansky and H. R. Nassour - November-December 1939]

Letter from Dr. Meyer Bodansky to Mr. H. R. Nassour, Jr. sending his greetings and thanks for a letter written in November, 1939. Mr. Nassour's attached letter states his regrets at not being able to see Dr. Bodansky the last time he visited Texas

A Techno-Economic Analysis of Sustainable Material Recovery Facilities: The Case of Al-Karak Solid Waste Sorting Plant, Jordan

Solid waste sorting facilities are constructed and operated to properly manage solid waste for both material and energy recovery. This paper investigates the possible technical and economic performance of the Al-Karak solid waste sorting plant in order to achieve financial sustainability and increase the profits that return on the plant to cover its operating costs. A standard procedure was followed to quantify and characterize the input materials of commercial solid waste by determining the recyclable materials in the sorting products. Thus, possible different equipment and material flows through the plant were proposed. An economic model was used in order to know the feasibility of the proposed options of the plant according to three economic factors, which are net present worth (NPW), return on investment (ROI), and payback period values. The results inferred that the characterization of the input materials contains a high portion of recyclable materials of paper, cardboard, plastic, and metals, which accounted for 63%. In this case, the mass of rejected waste to be landfilled was 9%. Results for the proposed options showed that the economic analysis is feasible when working loads on three and two shifts with ROI values of 4.4 and 3.5 with a payback period of the initial cost in 2 and 3 years, respectively. Working load on one shift was not feasible, which resulted in an ROI value of less than 2 and a payback period larger than 5 years. This paper recommended operating the sorting plant at a higher input feed with a working load on three shifts daily to ensure a maximum profit and to reduce the amount of commercial solid waste prior to landfilling through the concept of sorting and recycling