Search

Introduction: Subarachnoid hemorrhage (SAH) is a devastating disease. A third of the patients die and a large percentage of the survivors require support in daily living and suffers from reduced quality of life. As part of clinical practice for these patients, a cerebral microdialysis catheter may be placed to monitor cerebral metabolic function. Using this monitoring technique, the patients often demonstrate an increase in the lactate-pyruvate ratio, despite adequate supply of glucose and oxygen, which may be an indirect marker of mitochondrial dysfunction. We wanted to identify a possible mitochondrial dysfunction in a rat SAH model at different time points by directly measuring mitochondrial function in brain tissue ex vivo . Method: The pre-chiasmatic single injection model of SAH was used. Oroboros Oxygraph high resolution respirometry was used to evaluate the electron transport chain of the mitochondria. We also analyzed ROS generation simultaneously at the same time points using the Oroboros LED2 module. We measured tissue from the cortex and the hippocampus. Results: 45 rats at four different timepoints, 6-, 24-, 48- and 96 hours after surgery, were included. We identified a significant reduction in respiration through complexes I and II of the electron transport chain in hippocampal tissue at 96 hours after SAH compared to sham. The respiration of cortical tissue at the same time point was reduced compared to sham but did not reach significance. No differences were identified at other time points and no differences in ROS generation were identified. Conclusion: We conclude that the SAH model can be used as a suitable model to identify mitochondrial dysfunction and that the respiratory capacity of the electron transport chain is reduced in the hippocampus at 96 h post insult in this rat model of SAH.

Climate change communication spans multiple disciplines which in many cases have insufficient understanding of each other’s research traditions and, therefore, there has not been a solid interdisci...

Sodium fluoroacetate (FA) is a metabolic poison that systemically inhibits the tricarboxylic acid (TCA) cycle, causing energy deficiency and ultimately multi-organ failure. It poses a significant threat to society because of its high toxicity, potential use as a chemical weapon and lack of effective antidotal therapy. In this study, we investigated cell-permeable succinate prodrugs as potential treatment for acute FA intoxication. We hypothesized that succinate prodrugs would bypass FA-induced mitochondrial dysfunction, provide metabolic support, and prevent metabolic crisis during acute FA intoxication. To test this hypothesis, rats were exposed to FA (0.75 mg/kg) and treated with the succinate prodrug candidate NV354. Treatment efficacy was evaluated based on cardiac and cerebral mitochondrial respiration, mitochondrial content, metabolic profiles and tissue pathology. In the heart, FA increased concentrations of the TCA metabolite citrate (+ 4.2-fold, p 0.01) and lowered ATP levels (- 1.9-fold, p 0.001), confirming the inhibition of the TCA cycle by FA. High-resolution respirometry of cardiac mitochondria further revealed an impairment of mitochondrial complex V (CV)-linked metabolism, as evident by a reduced phosphorylation system control ratio (- 41%, p 0.05). The inhibition of CV-linked metabolism is a novel mechanism of FA cardiac toxicity, which has implications for drug development and which NV354 was unable to counteract at the given dose. In the brain, FA induced the accumulation of β-hydroxybutyrate (+ 1.4-fold, p 0.05) and the reduction of mitochondrial complex I (CI)-linked oxidative phosphorylation (OXPHOS

Digital platforms, with their ever-increasing reach and power, are reshaping many aspects of society. China is experiencing a platformization of society akin to what has occurred in the West. By mapping the algorithmic news distribution field in China, this study shows how the key players (including digital platforms, news organizations, and state regulators) compete, collaborate, and work symbiotically with each other in this changing ecology. We explore a particularly key player—Jinri Toutiao, led by ByteDance (parent company of the popular app TikTok)—as a case that exemplifies the platform logic in China’s news ecosystem and how it involves a delicate dance with the public and regulators in a politically restrictive environment. We find that the mutual shaping of platforms and society is not a given but rather a dynamic process. Indeed, we show that Toutiao’s tremendous success is partially because of the state’s laissez-faire policy in the earlier years, and that its move to assume greater social responsibility is a response to recent tightening of regulations. Amid widespread questions about the role and influence of Big Tech and platforms in society, the case of China enriches our understanding of the platformization of news outside the Western context.

Journalism and other institutions clash over automated news generation, algorithmic distribution and content ownership worldwide. AI policies are the main mechanisms that establish and organise the hierarchies among these institutions. Few studies, however, have explored the normative dimension of AI in policymaking in journalism, especially beyond the West. This case study inspects the copyright law's impact on AI innovation in newsrooms in the unexamined Chinese context. Using neo-institutional theory and policy network theory, the study investigates the Third Amendment to the Chinese Copyright Law, exemplary court cases regarding automated journalism copyright disputes (such as Tencent v. Yingxun and Film v. Baidu), and other supporting documents. The findings show how China's copyright legal framework separates authorship and ownership; defines "originality" and "creativity" in human-machine collaboration; and prioritises tech companies while undermining journalistic autonomy. We argue that the law's eager embrace of AI may give tech companies an advantage over news organisations that do not necessarily have a strategy to adopt AI. Moreover, it favours state-owned, resource-rich official media over the private sector. An implication of this shifting power dynamic is the possibility of privately owned news media being marginalised, resulting in even stronger state control over media production and information flow.

News dissemination online is driven by three gatekeeping logics: the gatekeeping logic of the news media (publishing), the gatekeeping logic of social actors (sharing), and the gatekeeping logic of platform algorithms (spreading), each guided by different values and with a different relationship to content. Using a reverse engineering approach, this study applies a 2015 dataset to empirically explore how a Facebook algorithm changed the overall composition of the news users saw, highlighting the ongoing issue of how the different gates and associated gatekeeping logics – especially that of platforms – influence news distribution. In contrast to previous studies, we find the relationship between news properties and the distribution of news online to be non-linear. Results point to Facebook's role in the overall composition of online news, both directly and in interaction with other gatekeepers. As news stories become more widely spread online, algorithmic logics take precedence over user behaviour and preferences.

Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4–8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood–brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.

Editorial offices are being shut down in small municipalities, raising the question of whether hyperlocal media can fill the gap left by legacy media. However, very little is known about the shape of this gap and thus to what extent it can be filled by hyperlocal media. To inform this line of research, this study asks: what happens to the news coverage of a municipality when there is no permanent presence of journalists? A quantitative content analysis (N = 606), measuring news topics, framing, style, original reporting and sourcing practices, was performed regarding the news coverage of 12 Swedish municipalities – six with editorial offices of a legacy media organisation and six without. The results indicate that municipalities receive less original coverage, community news receives less attention and institutional actors are quoted more often when there is no permanent presence of journalists. Implications for communities and hyperlocal media are discussed.

By fusing key incongruities between New Materialism and OOO, this chapter offers a re-reading of the lyrical subject in Sylvia Plath’s poetry, showing the life of Plath’s subject to be in various ways entwined with the life of things. More specifically, the chapter offers a close reading of Plath’s late poem “Tulips”, which is selected as a prime example of how nonhuman things – for Plath – are cast as hostile and intrusive, intervening with egotistical notions of subjecthood, but at the same time are shown to be the very thing that sustains and grounds the subject. To appreciate this paradoxical nature of things in Plath’s poetry, the chapter mixes the thing-ontology of Martin Heidegger, New Materialism and OOO in order to show that nonhuman things exist in a tension between the relational and non-relational. As such, the chapter vouches for the use of literature to challenge and complicate theoretical assumptions, especially when it comes to thinking human-nonhuman-relations.

All phase III trials evaluating medical treatments for traumatic brain injury (TBI), performed to date, have failed. To facilitate future success there is a need for novel outcome metrics that can bridge pre-clinical studies to clinical proof of concept trials. Our objective was to assess diffusion tensor imaging (DTI) and biofluid-based biomarkers as efficacy outcome metrics in a large animal study evaluating the efficacy of cyclosporine in TBI. This work builds on our previously published study that demonstrated a reduced volume of injury by 35% with cyclosporine treatment based on magnetic resonance imaging (MRI) results. A focal contusion injury was induced in piglets using a controlled cortical impact (CCI) device. Cyclosporine in a novel Cremophor/Kolliphor EL-free lipid emulsion, NeuroSTAT, was administered by continuous intravenous infusion for 5 days. The animals underwent DTI on day 5. Glial fibrillary acidic protein (GFAP), as a measure of astroglia injury, and neurofilament light (NF-L), as a measure of axonal injury, were measured in blood on days 1, 2, and 5, and in cerebrospinal fluid (CSF) on day 5 post-injury. Normalized fractional anisotropy (FA) was significantly (

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) reportedly elevates arterial blood pressure (ABP) during non-traumatic cardiac arrest. Objectives This randomized, blinded trial of cardiac arrest in pigs evaluated the effect of automated REBOA two minutes after balloon inflation on ABP (primary endpoint) as well as arterial blood gas values and markers of cerebral haemodynamics and metabolism. Methods Twenty anesthetized pigs were randomized to REBOA inflation or sham-inflation (n = 10 in each group) followed by insertion of invasive monitoring and a novel, automated REBOA catheter (NEURESCUE® Catheter & NEURESCUE® Assistant). Cardiac arrest was induced by ventricular pacing. Cardiopulmonary resuscitation was initiated three min after cardiac arrest, and the automated REBOA was inflated or sham-inflated (blinded to the investigators) five min after cardiac arrest. Results In the inflation compared to the sham group, mean ABP above the REBOA balloon after inflation was higher (inflation: 54 (95%CI: 43–65) mmHg; sham: 44 (33–55) mmHg; P = 0.06), and diastolic ABP was higher (inflation: 38 (29–47) mmHg; sham: 26 (20–33) mmHg; P = 0.02), and the arterial to jugular oxygen content difference was lower (P = 0.04). After return of spontaneous circulation, mean ABP (inflation: 111 (95%CI: 94–128) mmHg; sham: 94 (95%CI: 65–123) mmHg; P = 0.04), diastolic ABP (inflation: 95 (95%CI: 78−113) mmHg; sham: 78 (95%CI: 50−105) mmHg; P = 0.02), CPP (P = 0.01), and brain tissue oxygen tension (inflation: 315 (95%CI: 139−491)% of baseline; sham: 204 (95%CI: 75−333)%; P = 0.04) were higher in the inflation compared to the sham group. Conclusion Inflation of REBOA in a porcine model of non-traumatic cardiac arrest improves central diastolic arterial pressure as a surrogate marker of coronary artery pressure, and cerebral perfusion. Institutional protocol number 2017-15-0201-01371.

Background Hyperoxia during cardiopulmonary resuscitation (CPR) may lead to oxidative injury from mitochondrial‐derived reactive oxygen species, despite guidelines recommending 1.0 inspired oxygen during CPR . We hypothesized exposure to 1.0 inspired oxygen during CPR would result in cerebral hyperoxia, higher mitochondrial‐derived reactive oxygen species, increased oxidative injury, and similar survival compared with those exposed to 21% oxygen. Methods and Results Four‐week‐old piglets (n=25) underwent asphyxial cardiac arrest followed by randomization and blinding to CPR with 0.21 (n=10) or 1.0 inspired oxygen (n=10) through 10 minutes post return of spontaneous circulation. Sham was n=5. Survivors received 4 hours of protocolized postarrest care, whereupon brain was obtained for mitochondrial analysis and neuropathology. Groups were compared using Kruskal‐Wallis test, Wilcoxon rank‐sum test, and generalized estimating equations regression models. Both 1.0 and 0.21 groups were similar in systemic hemodynamics and cerebral blood flow, as well as survival (8/10). The 1.0 animals had relative cerebral hyperoxia during CPR and immediately following return of spontaneous circulation (brain tissue oxygen tension, 85% [interquartile range, 72%–120%] baseline in 0.21 animals versus 697% [interquartile range, 515%–721%] baseline in 1.0 animals; P =0.001 at 10 minutes postarrest). Cerebral mitochondrial reactive oxygen species production was higher in animals treated with 1.0 compared with 0.21 ( P P P Conclusions Exposure to 1.0 inspired oxygen during CPR caused cerebral hyperoxia during resuscitation, and resultant increased mitochondrial‐derived reactive oxygen species and oxidative injury following cardiac arrest.

Background Despite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first. Methods One-month-old piglets (n = 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10–20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO2]) and noninvasive (diffuse correlation spectroscopy and diffuse optical spectroscopy) measurements of CBF and cerebral tissue oxygenation were simultaneously recorded. Effects of subsequent epinephrine doses were compared to the first. Results With the first epinephrine dose during CPR, CBF and cerebral tissue oxygenation increased by > 10%, as measured by each of the invasive and noninvasive measures (p p p Conclusions This model suggests that epinephrine increases CBF and cerebral tissue oxygenation, but that effects wane following the third dose. Noninvasive measurements of neurological health parameters hold promise for developing and directing resuscitation strategies.

This study investigates the kinds of transparency that appeal to different parts of the public and the extent to which transparency can be a remedy for declining trust in journalism. It uses a representative survey of Swedes, and the results show that there are three distinct forms of transparency, including the previously unreported ambient transparency, and that they appeal to different people. News consumption or social media use has little or no effect on transparency. The strongest positive effect on transparency comes from appreciation of the current quality of journalistic performance, high trust in journalists and media, and having news media and authorities as the preferred channels of information. Those most skeptical about journalism are also least positive about transparency. The results suggest that transparency has very limited reach as a cure for declining trust in, and the trustworthiness of, journalism, possibly since the acts of transparency themselves remain non-transparent.

Transparency has emerged as an ethical principle in contemporary journalism and is contended to improve accountability and credibility by journalists and scholars alike. However, to date, few attempts have been made to record the public’s views on transparency. This study enriches current knowledge by using data from an experiment, survey and focus groups in Sweden collected between 2013 and 2015. Overall, the results suggest that the respondents are not particularly moved by transparency in any form; it does not produce much effect in the experiments and is not brought up in the focus groups. While that is the key finding of this study, it should also be noted that various forms of user participation are evaluated negatively, while providing hyperlinks, explaining news selection and framing, and correcting errors are viewed positively. Implications for journalism practice and research are discussed.

Attempts to define journalism are often normative in nature but do not add to our theoretical understanding of what journalism is. There is a need for journalism scholarship to recognize explicitly ...

The article presents a network analysis of 22,861,013 geocoded external hyperlinks, collected from 230 Danish, 220 Norwegian and 208 Swedish news websites in 2016. The analysis asks what the structural properties of the Scandinavian media systems—including its geography and ownership structures—mean for news outlets’ centrality within the hyperlinked news ecology. The analysis finds that whereas incumbent legacy media occupy central positions, about one third of the network is absent from the hyperlinked interaction, primarily local, independently owned newspapers. A multiple linear regression analysis shows that national distribution and corporate ownership correlates to network centrality more than other predictors. As brokers in the network consist of the large, legacy, capital-based news organisations, hyperlink connectivity is primarily characterised by proximity to the centres of power, corporate ownership, agenda setting incumbency and national distribution. The article presents a network analysis of 22,861,013 geocoded external hyperlinks, collected from 230 Danish, 220 Norwegian and 208 Swedish news websites in 2016. The analysis asks what the structural properties of the Scandinavian media systems—including its geography and ownership structures—mean for news outlets’ centrality within the hyperlinked news ecology. The analysis finds that whereas incumbent legacy media occupy central positions, about one third of the network is absent from the hyperlinked interaction, primarily local, independently owned newspapers. A multiple linear regression analysis shows that national distribution and corporate ownership correlates to network centrality more than other predictors. As brokers in the network consist of the large, legacy, capital-based news organisations, hyperlink connectivity is primarily characterised by proximity to the centres of power, corporate ownership, agenda setting incumbency and national distribution.

Many in-hospital cardiac arrests are precipitated by hypotension, often associated with systemic inflammation. These patients are less likely to be successfully resuscitated, and novel approaches to their treatment are needed.To determine if the addition of inhaled nitric oxide (iNO) to hemodynamic-directed cardiopulmonary resuscitation (HD-CPR) would improve short-term survival from cardiac arrest associated with shock and systemic inflammation.In 3-month-old swine (n = 21), LPS was intravenously infused, inducing systemic hypotension. Ventricular fibrillation was induced, and animals were randomized to blinded treatment with either: 1) HD-CPR with iNO, or 2) HD-CPR without iNO. During HD-CPR, chest compression depth was titrated to peak aortic compression pressure of 100 mm Hg, and vasopressor administration was titrated to coronary perfusion pressure greater than or equal to 20 mm Hg. Defibrillation attempts began after 10 minutes of resuscitation. The primary outcome was 45-minute survival.The iNO group had higher rates of 45-minute survival (10 of 10 vs. 3 of 11; P = 0.001). During cardiopulmonary resuscitation, the iNO group had lower pulmonary artery relaxation pressure (mean ± SEM, 10.9 ± 2.4 vs. 18.4 ± 2.4 mm Hg; P = 0.03), higher coronary perfusion pressure (21.1 ± 1.5 vs. 16.9 ± 1.0 mm Hg; P = 0.005), and higher aortic relaxation pressure (36.6 ± 1.6 vs. 30.4 ± 1.1 mm Hg; P 0.001) despite shallower chest compressions (5.88 ± 0.25 vs. 6.46 ± 0.40 cm; P = 0.02) and fewer vasopressor doses in the first 10 minutes (median, 4 [interquartile range, 3-4] vs. 5 [interquartile range, 5-6], P = 0.03).The addition of iNO to HD-CPR in LPS-induced shock-associated cardiac arrest improved short-term survival and intraarrest hemodynamics.

OBJECTIVESControversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia–reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model.METHODSTwenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis.RESULTSDHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P CONCLUSIONSDHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.