5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

Rotavirus infection

Q1Q1Artículo original1-16Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children 200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of the neurotransmitter serotonin from intestinal sensory enterochromaffin cells, in vitro and ex vivo. Interestingly, serotonin is known to be a mediator of both diarrhea and vomiting. Moreover, mice pups infected with rotavirus responded with central nervous system (CNS) activation in brain structures associated with vomiting, thus indicating a cross-talk between the gut and brain in rotavirus disease. Our finding that rotavirus infection activates the CNS led us to address the hypothesis that rotavirus infection not only activates the vagus nerve to stimulate vomiting, but also suppresses the inflammatory response via the cholinergic anti-inflammatory pathway, both of which are mediated by activated vagal afferent nerve signals into the brain stem. We found that mice lacking an intact vagus nerve, and mice lacking the α7 nicotine acetylcholine receptor (nAChR), being involved in cytokine suppression from macrophages, responded with a higher inflammatory response. Moreover, stimulated cytokine release from macrophages, by the rotavirus toxin NSP4, could be attenuated by nicotine, an agonist of the α7 nAChR. Thus, it seems most reasonable that the cholinergic anti-inflammatory pathway contributes to the limited inflammatory response during rotavirus infection. Moreover, rotavirus-infected mice displayed increased intestinal motility at the onset of diarrhea, which was not associated with increased intestinal permeability. The increased motility and diarrhea in infant mice could be attenuated by drugs acting on the enteric nervous system, indicating the importance and contribution of nerves in the rotavirus mediated disease. In conclusion, this thesis provides further insight into the pathophysiology of diarrhea and describe for the first time how rotavirus and host cross-talk to induce the vomiting reflex and limit inflammation. Results from these studies strongly support our hypothesis that serotonin and activation of the enteric nervous system and CNS contributes to diarrhea, vomiting and suppression of the inflammatory response in rotavirus disease

Rotavirus Sickness Symptoms: Manifestations of Defensive Responses from the Brain

Rotavirus is infamous for being extremely contagious and for causing diarrhea and vomiting in infants. However, the symptomology is far more complex than what could be expected from a pathogen restricted to the boundaries of the small intestines. Other rotavirus sickness symptoms like fever, fatigue, sleepiness, stress, and loss of appetite have been clinically established for decades but remain poorly studied. A growing body of evidence in recent years has strengthened the idea that the evolutionarily preserved defensive responses that cause rotavirus sickness symptoms are more than just passive consequences of illness and rather likely to be coordinated events from the central nervous system (CNS), with the aim of maximizing the survival of the individual as well as the collective group. In this review, we discuss both established and plausible mechanisms of different rotavirus sickness symptoms as a series of CNS responses coordinated from the brain. We also consider the protective and the harmful nature of these events and highlight the need for further and deeper studies on rotavirus etiology

Vietnamesiska sjuksköterskors uppfattning om patientsäkerhet.

Introduction: Building a safety net, leadership and containing quality, are some of many responsibilities that comes with the profession nursing. To maintain health care of highest quality knowledge about patient safety is important. Patient safety means prevent medical errors that may cause the patient physical or psychological damage or in worst case scenario, death. Aim: To describe Vietnamese nurses’ conceptions of patient safety. Method: The study had a qualitative design. Data were collected from interviewing nurses at Hué University Hospital with open-ended questions. The collected data has been transcribed and condensed to categories through content analysis to find key sentences which explained Vietnamese nurses’ conception of patient safety. Result: Data analysis regarding Vietnamese nurse´s conception of patient safety resulted in seven categories which affect patient safety in Hue University Hospital, Equipment effecting the patient safety, Knowledge to provide safer care, Procedures used to increase patient safety, Infections in relation to poor patient safety, Nurses´ conception of communication, Documentation effecting patient safety and Inadequate number of nurses. Conclusion: This study shows that lack of good hygiene, insufficient equipment and the great number of patients are the most common factors to affect the patient safety in a negative way in Vietnam. The study shows that the nurses are well aware of what factors affecting the patient safety as well as how to improve patient safety

Understanding the Central Nervous System Symptoms of Rotavirus : A Qualitative Review

This qualitative review on rotavirus infection and its complications in the central nervous system (CNS) aims to understand the gut-brain mechanisms that give rise to CNS driven symptoms such as vomiting, fever, feelings of sickness, convulsions, encephalitis, and encephalopathy. There is substantial evidence to indicate the involvement of the gut-brain axis in symptoms such as vomiting and diarrhea. The underlying mechanisms are, however, not rotavirus specific, they represent evolutionarily conserved survival mechanisms for protection against pathogen entry and invasion. The reviewed studies show that rotavirus can exert effects on the CNS trough nervous gut-brain communication, via the release of mediators, such as the rotavirus enterotoxin NSP4, which stimulates neighboring enterochromaffin cells in the intestine to release serotonin and activate both enteric neurons and vagal afferents to the brain. Another route to CNS effects is presented through systemic spread via lymphatic pathways, and there are indications that rotavirus RNA can, in some cases where the blood brain barrier is weakened, enter the brain and have direct CNS effects. CNS effects can also be induced indirectly as a consequence of systemic elevation of toxins, cytokines, and/or other messenger molecules. Nevertheless, there is still no definitive or consistent evidence for the underlying mechanisms of rotavirus-induced CNS complications and more in-depth studies are required in the future.Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-02862]</p

Remote Leadership

Introduction At the start of 2020 Sweden gets their first documented case of Covid -19. On March 16th the Public Health Agency of Sweden recommended that schools and universities should conduct their education on distance mode. These recommendations would also apply to businesses all around Sweden where it is possible to work remotely. Previous studies have shown that working remotely requires that leadership must take more responsibility. Additionally, the need for clear management control and communication. Purpose The purpose of this study is to research how management control and communication works and have changed within knowledge intensive organizations where daily operations has gone on distance mode due to the corona pandemic. Method The research has been conducted using a qualitative method where both managers and employees have been interviewed. The interviewed people represent three different organizations, a management company, the industrial unit within the Swedish Environmental Protection Agency and a legal unit within Swedish Public Employment Service. Result and contribution According to our research, remote work during the Covid-19 pandemic has led to informal meetings on the workplace has been heavily reduced or completely seized. This change has affected managers ability to retain a healthy relationship to their employees. The study show that a management control based on trust and a leadership based on trust has been an advantage, especially within knowledge intensive organizations. The underlying challenge for the managers has been missing communication and knowledge sharing.Inledning  Den 31 januari 2020 får Sverige sitt första konstaterade fall av Covid-19. Den 16 Mars presenterar Folkhälsomyndigheten rekommendationerna om att svenska gymnasieskolor, universitet, högskolor och övrig utbildning att ske på distans. Dessa rekommendationer kommer även att gälla för samtliga verksamheter i Sverige som har möjlighet att arbeta på distans. Under distansarbete visar tidigare forskningen på ett ökat behov av en medveten och välutvecklad arbetsledning, samt behovet av en tydligare styrning och kommunikation.  Syfte  Syftet med uppsatsen är att studera hur styrningen och kommunikationen fungerar samt förändrats inom kunskapsorganisationer där verksamheten har gått över till distansarbete, som en följd av pandemin.   Metod  Undersökningen är utförd med en kvalitativ metod där vi har intervjuat chefer och medarbetare. De olika kunskapsorganisationer vi undersökt är ett managementbolag, Industrienheten inom Naturvårdsverket och rättsavdelningen på Arbetsförmedlingen. Resultat och bidrag Distansarbetet har enligt samtliga respondenter, lett till att informella möten på arbetsplatsen minskat eller helt upphört. Det har påverkat chefernas förmåga att upprätthålla en viktig relation till medarbetarna, men även inverkat på informationsflödet. Denna studie visar att en tillitsbaserad styrning och ett tillitsbaserat ledarskap är fördelaktigt under distansarbetet, speciellt inom kunskapsorganisationer. De stora utmaningarna för de chefer som intervjuats kan härledas till bortfall av kommunikation och kunskapsdelning.

Organizational Subculture And Circular Economy : A Case Study Of Circular Purchasing In The Municipality Of Malmö

To this day, literature has mainly been focused on the implementation of Circular Economy in the business sector, but as more and more nations adopt the approach of Circular Economy there is a need to further research the role of public agencies in this transition. The City of Malmö is seen as a progressive actor in the field of climate issues and has integrated sustainability objectives widely across the entire organizational culture. However, behaviors and understandings of sustainability are not only connected to organizational culture, but also to organizational subculture. To successfully implement sustainable and circular practices in a public agency there is therefore a need to understand organizational subculture. To initiate the transition towards a circular economy, the municipality of Malmö procured a contract in 2019 that gave the departments of the city an opportunity to purchase circular furniture instead of new. On this foundation, the purpose of this paper was to qualitatively explore what possible subcultures that exist in the City of Malmö and how subcultures can influence circular purchasing practices within a public agency. Empirical data was gathered from semi-structured interviews, individual Organizational Culture Assessment Instrument surveys and strategic documents from five of Malmö’s departments. By analyzing the collected data from the theoretical lens of organizational culture, subculture and Competing Values Framework, this study reached three major findings. Firstly, the study indicates the existence of several organizational subcultures within the City of Malmö, that in various ways influence circular purchasing practices within the municipality. Secondly, circular purchasing is not only affected by subcultural values but also individual values and understandings of sustainability. Finally, multiple barriers and motivators for purchasing circular furniture were identified, where the main barrier shows a cultural and physical distance between the umbrella organization of the municipality and the departments. 2.12.0.02.12.0.0</p

Rotavirus Downregulates Tyrosine Hydroxylase in the Noradrenergic Sympathetic Nervous System in Ileum, Early in Infection and Simultaneously with Increased Intestinal Transit and Altered Brain Activities

Previous studies have investigated the mechanisms of rotavirus diarrhea mainly by focusing on intrinsic intestinal signaling. Although these observations are compelling and have provided important mechanistic information on rotavirus diarrhea, no information is available on how the gut communicates with the central nervous system (CNS) during rotavirus infection or on how this communication initiates sickness symptoms. While rotavirus diarrhea has been considered to occur only due to intrinsic intestinal effects within the enteric nervous system, we provide evidence for central nervous system control underlying the clinical symptomology. Our data visualize infection by large-scale three-dimensional (3D) volumetric tissue imaging of a mouse model and demonstrate that rotavirus infection disrupts the homeostasis of the autonomous system by downregulating tyrosine hydroxylase in the noradrenergic sympathetic nervous system in ileum, concomitant with increased intestinal transit. Interestingly, the nervous response was found to occur before the onset of clinical symptoms. In adult infected animals, we found increased pS6 immunoreactivity in the area postrema of the brain stem and decreased phosphorylated STAT5-immunoreactive neurons in the bed nucleus of the stria terminalis, which has been associated with autonomic control, including stress response. Our observations contribute to knowledge of how rotavirus infection induces gut-nerve-brain interaction early in the disease. IMPORTANCE Previous studies have investigated the mechanisms of rotavirus diarrhea mainly by focusing on intrinsic intestinal signaling. Although these observations are compelling and have provided important mechanistic information on rotavirus diarrhea, no information is available on how the gut communicates with the central nervous system (CNS) during rotavirus infection or on how this communication initiates sickness symptoms. We show that rotavirus infection presymptomatically disrupts the autonomic balance by downregulating the noradrenergic sympathetic nervous system in ileum, concomitant with increased intestinal transit and altered CNS activity, particularly in regions associated with autonomic control and stress response. Altogether, these observations reveal that the rotavirus-infected gut communicates with the CNS before the onset of diarrhea, a surprising observation that brings a new understanding of how rotavirus gives rise to sickness symptoms.Funding Agencies|Swedish Research Council [2018-02862, 2020-06116]; Hjarnfonden [PS2021-0063]</p

Viral Gastroenteritis: Sickness Symptoms and Behavioral Responses

Viral infections have a major impact on physiology and behavior. The clinical symptoms of human rotavirus and norovirus infection are primarily diarrhea, fever, and vomiting, but several other sickness symptoms, such as nausea, loss of appetite, and stress response are never or rarely discussed. These physiological and behavioral changes can be considered as having evolved to reduce the spread of the pathogen and increase the chances of survival of the individual as well as the collective. The mechanisms underlying several sickness symptoms have been shown to be orchestrated by the brain, specifically, the hypothalamus. In this perspective, we have described how the central nervous system contributes to the mechanisms underlying the sickness symptoms and behaviors of these infections. Based on published findings, we propose a mechanistic model depicting the role of the brain in fever, nausea, vomiting, cortisol-induced stress, and loss of appetite.Funding Agencies|Swedish Research Council [2018-02862, 2020-06116]; Hjarnfonden [PS2021-0063]; Region OEstergoetland [ALF ROE-969520]</p