Global Connectivity and Function of Descending Spinal Input Revealed by 3D Microscopy and Retrograde Transduction

The brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. This complexity presents a major challenge to interpreting functional outcomes from therapies that target supraspinal connectivity after injury or disease, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate that injection of AAV2-Retro to the cervical spinal cord of adult female mice results in highly efficient transduction of supraspinal populations throughout the brainstem, midbrain, and cortex. Some supraspinal populations, including corticospinal and rubrospinal neurons, were transduced with \u3e90% efficiency, with robust transgene expression within 3 d of injection. In contrast, propriospinal and raphe spinal neurons showed much lower rates of retrograde transduction. Using tissue clearing and light-sheet microscopy we present detailed visualizations of descending axons tracts and create a mesoscopic projectome for the spinal cord. Moreover, chemogenetic silencing of supraspinal neurons with retrograde vectors resulted in complete and reversible forelimb paralysis, illustrating effective modulation of supraspinal function. Retrograde vectors were also highly efficient when injected after spinal injury, highlighting therapeutic potential. These data provide a global view of supraspinal connectivity and illustrate the potential of retrograde vectors to parse the functional contributions of supraspinal inputs

Supply Chains and Corporate Social Responsibility Orientation: An Interpretive Structural Modeling Approach

Corporate social responsibility (CSR) operations are becoming increasingly important for businesses throughout the world. It is critical to understand how stakeholders perceive these actions to achieve the intended CSR advantages. The nature of CSR motivation has been extensively discussed, yet there are still gaps in the literature, including CSR orientation. Individual enterprises are no longer pitted against one another in modern global competitiveness; instead, a company’s supply chains (SCs) are opposed to those of its competitors. To be competitive, SC partners must be aware of stakeholders’ expectations, which are increasingly focused on sustainable practices. Apart from financial performance, organizations are increasingly held liable for the environmental and social impacts of not just their own operations, but also the operations of their whole SCs, which may include second, third, or higher-tier suppliers. As a result, from raw material extraction through product recycling, an integrated approach to SC management necessitates the development and maintenance of relational capacities across SC partners. In SC collaborations, a company’s commitment to CSR can be a critical aspect. Managing CSR becomes more difficult as SCs get more sophisticated and multitiered, and it attracts greater attention. In this paper, the key drivers that shape CSR orientation are identified based on the literature and are classified into three categories: internal, external, and SC related. A conceptual model is formulated using interpretative structural modeling and MICMAC to identify interrelationships among these drivers, based on the opinions of experts from the Greek market and academia. Keywords: supply chain, corporate social responsibility, drivers, interpretive structural modeling, Greec

Design Principles for Closed Loop Supply Chains

In this paper we study design principles for closed loop supply chains. Closed loop supply chains aim at closing material flows thereby limiting emission and residual waste, but also providing customer service at low cost. We study 'traditional' and 'new' design principles known in the literature. It appears that setting up closed loop supply chains requires some additional design principles because of sustainability requirements. At the same time however, we see that traditional principles also apply. Subsequently we look at a business situation at Honeywell. Here, only a subset of the relevant design principles is applied. The apparent low status of reverse logistics may provide an explanation for this. To some extent, the same mistakes are made again as were 20 years ago in, for instance, inbound logistics. Thus, obvious improvements can be made by applying traditional principles. Also new principles, which require a life cycle driven approach, need to be applied. This can be supported by advanced management tools such as LCA and LCC.reverse logistics;case-study;closed loop supply chains

Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

Context: Ischemia-reperfusion injury is a fascinating topic which has drawn a lot of interest in the last several years. Hepatic ischemia reperfusion injury may occur in a variety of clinical situations. These include transplantation, liver resection, trauma, and vascular surgery. Evidence Acquisition: The purpose of this review was to outline the molecular mechanisms underlying hepatic I/R injury and present the latest approaches, both surgical and pharmacological, regarding the prevention of it. A comprehensive electronic literature search in MEDLINE/PubMed was performed to identify relative articles published within the last 2 years. Results: The basic mechanism of hepatic ischemia – reperfusion injury is one of blood deprivation during ischemia, followed by the return of flow during reperfusion. It involves a complex series of events, such as mitochondrial deenergization, adenosine-5'-triphosphate depletion, alterations of electrolyte homeostasis, as well as Kupffer cell activation, oxidative stress changes and upregulation of proinflammatory cytokine signaling. The great number of variable pathways, with several mediators interacting with each other, leads to a high number of candidates for potential therapeutic intervention. As far as surgical approaches are concerned, the modification of existing clamping techniques and the ischemic preconditioning are the most promising techniques till recently. In the search for novel techniques of protecting against hepatic ischemia reperfusion injury, many different strategies have been used in experimental models. The biggest part of this research lies around antioxidant therapy, but other potential solutions have been explored as well. Conclusions: The management of hepatic trauma, in spite of the fact that it has become increasingly nonoperative, there still remains the possibility of hepatic resection in the hepatic trauma setting, especially in severe injuries. Hence, clinicians should be familiar with the concept of hepatic ischemia-reperfusion injury and respond appropriately and timely