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| 2. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 4. |
- Pauls, Dennis, et al.
(författare)
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Endocrine signals fine-tune daily activity patterns in Drosophila
- 2021
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 31:18, s. 4076-
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Tidskriftsartikel (refereegranskat)abstract
- Animals need to balance competitive behaviors to maintain internal homeostasis. The underlying mechanisms are complex but typically involve neuroendocrine signaling. Using Drosophila, we systematically manipulated signaling between energy-mobilizing endocrine cells producing adipokinetic hormone (AKH), octopaminergic neurons, and the energy-storing fat body to assess whether this neuroendocrine axis involved in starvation-induced hyperactivity also balances activity levels under ad libitum access to food. Our results suggest that AKH signals via two divergent pathways that are mutually competitive in terms of activity and rest. AKH increases activity via the octopaminergic system during the day, while it prevents high activity levels during the night by signaling to the fat body. This regulation involves feedback signaling from octopaminergic neurons to AKH-producing cells (APCs). APCs are known to integrate a multitude of metabolic and endocrine signals. Our results add a new facet to the versatile regulatory functions of APCs by showing that their output contributes to shape the daily activity pattern under ad libitum access to food.
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| 5. |
- Süess, Philip, 1988-
(författare)
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Unraveling the regulatory mechanisms of pupal diapause termination
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diapause is an essential part of many insect’s life cycle and is a developmental halt induced by environmental cues in advance of deteriorating conditions. Insects typically enter diapause to avoid unfavorable environmental conditions like low temperatures, poor food quality and the absence of conspecifics. The aim of my PhD thesis was to describe how diapause is regulated and what determines its termination timing in the green-veined white butterfly Pieris napi. Answers to these questions deepens the knowledge about species distribution and population dynamics in times of a rapidly changing climate. In ectothermic insects, developmental rate generally follows a thermal performance curve (TPC) with higher temperatures leading to a faster development. However, in the diapause of P. napi low temperatures result in a higher proportion of terminations. In Chapter I, I assessed the thermal performance of diapause termination rate in P. napi by exposing them to several different temperature treatments. The diapause termination rate follows a left-shifted TPC with an optimum termination rate at 0°C and slower termination rates toward higher temperatures. This left-shifted TPC prevents the precocious termination of diapause in autumn while at the same time enabling populations to remain synchronized over a long period. Development in insects is regulated by the major developmental hormones, insulins, juvenile hormones, ecdysone, and the prothoracicotropic hormone (PTTH). The pupal diapause is regulated by the neuropeptide PTTH produced in the brain and ecdysone produced in the prothoracic glands. In Chapter II I studied this hormonal axis by assessing PTTH levels and injections with 20-hydroxyecdysone (20E), the active form of the ecdysone pathway. The PTTH neuropeptide shows diapause stage dependent changes to haemolymph levels and intracellular structure and the sensitivity to 20E returns in a time- and temperature dependent manner correlating with diapause termination progression. This indicates that diapause termination timing is regulated by the PTTH ecdysone axis and that the ecdysteroid receptor has a central part in the regulation. Diapause is a prolonged period without the ability to replenish energy resources, insects therefore accumulate resources before diapause and reduce the metabolic rate to a minimum. In Chapter III, I investigated how the diapause physiology as well as the reduced metabolic rate affect the mode of respiration. Respiratory patterns change with diapause stages and in diapause, discontinuous gas exchange is defended even at high temperatures, supporting the finding that the diapause physiology affects the metabolic rate and with it the respiratory patterns. In Chapter IV I followed up the lead from Chapter II and tested a hypothesis on the hormonal regulation of diapause termination in which the transcription factor Foxo, the ecdysteroid receptor as well as insulin interact to regulate ecdysone sensitivity. While many findings in the transcriptome and the protein levels support the hypothesis we need further investigations into this mechanism. Furthermore, the protein levels of most proteins studied do not correlate with the mRNA levels, and while this has been described under direct developing conditions too it would be interesting to study where those different levels stem from. These findings show that the three levels, temperature, metabolic rate and the hormonal pathways are tightly linked to the diapause physiology and are most likely involved in the regulation of diapause termination timing.
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| 6. |
- Zandawala, Meet, et al.
(författare)
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A neuroendocrine pathway modulating osmotic stress in Drosophila
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown of CrzR in Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila.
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