Pain after total knee arthroplasty (TKA) is a well‐known clinical problem potentially delaying ambulation and recovery. Perioperative glucocorticoids reduce pain and facilitate early recovery, but ...the optimal timing and dose are still unknown. High pain catastrophizers have an increased risk of poorly controlled postoperative pain, and moderate to severe pain at 24 h is associated with a risk of pain relapse at 48 h. To evaluate the effect of a repeat moderate dose of glucocorticoids after TKA in high pain catastrophizers presenting with moderate to severe pain 24 h postoperatively, having received preoperative high‐dose glucocorticoids. High pain catastrophizers (Pain Catastrophizing Scale > 20) undergoing TKA are screened 24 h postoperatively and are included if they experience moderate to severe pain (VAS > 30) during a 5 m walk test. The included patients will receive either oral 24 mg dexamethasone (n = 55) or placebo (n = 55) on the evening of Day 1 (~30–37 h) after surgery. In addition, patients receive a standard multimodal analgesic regimen, including paracetamol, celecoxib, local infiltration analgesia, and preoperative dexamethasone (1 mg/kg). Patients will fill out a pain diary for 7 days after surgery. The primary outcome is moderate to severe pain (VAS > 30) during a 5 m walk test on the morning of Day 2 after surgery. The secondary outcomes include cumulated pain at rest and during ambulation, cumulated use of rescue analgesics, quality of sleep, lethargy, dizziness, nausea, satisfaction with the analgesic regimen, length of stay, morbidity, mortality, and reasons for readmissions. Follow‐up is at 8 and 30 days. The data from this study will provide evidence for the effect of a repeated dose of dexamethasone as an analgesic adjuvant in patients undergoing TKA with a high risk of postoperative pain.
Disruptions of brain energy and neurotransmitter metabolism are associated with several pathological conditions including neurodegenerative diseases such as Alzheimer’s disease. Transgenic rodent ...models, and in vitro preparations hereof, are often applied for studying pathological aspects of brain metabolism. However, despite the conserved cerebral development across mammalian species, distinct differences in cellular composition and structure may influence metabolism of the rodent and human brain. To address this, we investigated the metabolic function of acutely isolated brain slices and non-synaptic mitochondria obtained from the cerebral cortex of mice and neurosurgically resected neocortical tissue of humans. Utilizing dynamic isotope labeling with
13
C-enriched metabolic substrates, we show that metabolism of glucose, acetate, β-hydroxybutyrate, and glutamine operates at lower rates in human cerebral cortical slices when compared to mouse slices. In contrast, human cerebral cortical slices display a higher capacity for converting exogenous glutamate into glutamine, which subsequently supports neuronal GABA synthesis, whereas mouse slices primarily convert glutamate into aspartate. In line with the reduced metabolic rate of the human brain slices, isolated non-synaptic mitochondria of the human cerebral cortex have a lower oxygen consumption rate when provided succinate as substrate. However, when provided pyruvate and malate, human mitochondria display a higher coupled respiration and lower proton leak, signifying a more efficient mitochondrial coupling compared to mouse mitochondria. This study reveals key differences between mouse and human brain metabolism concerning both neurons and astrocytes, which must be taken into account when applying in vitro rodent preparations as a model system of the human brain.
Trophic Strategies of Unicellular Plankton Chakraborty, Subhendu; Nielsen, Lasse Tor; Andersen, Ken H.
The American naturalist,
04/2017, Letnik:
189, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Unicellular plankton employ trophic strategies ranging from pure photoautotrophs over mixotrophy to obligate heterotrophs (phagotrophs), with cell sizes from 10−8 to 1 μg C. A full understanding of ...how trophic strategy and cell size depend on resource environment and predation is lacking. To this end, we develop and calibrate a trait-based model for unicellular planktonic organisms characterized by four traits: cell size and investments in phototrophy, nutrient uptake, and phagotrophy. We use the model to predict how optimal trophic strategies depend on cell size under various environmental conditions, including seasonal succession. We identify two mixotrophic strategies: generalist mixotrophs investing in all three investment traits and obligate mixotrophs investing only in phototrophy and phagotrophy. We formulate two conjectures: (1) most cells are limited by organic carbon; however, small unicellulars are colimited by organic carbon and nutrients, and only large photoautotrophs and smaller mixotrophs are nutrient limited; (2) trophic strategy is bottom-up selected by the environment, while optimal size is top-down selected by predation. The focus on cell size and trophic strategies facilitates general insights into the strategies of a broad class of organisms in the size range from micrometers to millimeters that dominate the primary and secondary production of the world’s oceans.
Summary
In a well‐defined fast‐track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra‐operative local anaesthetic infiltration and oral celecoxib, ...gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1–10 and 30 days postoperatively. Fast‐track total hip and knee arthroplasty with early discharge (< 3 days) resulted in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30–59 mm), and 16% severe pain (VAS ≥ 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation.
Polymerase chain reaction (PCR) and antigen tests have been used extensively for screening during the severe acute respiratory syndrome coronavirus 2 pandemics. However, the real‐world sensitivity ...and specificity of the two testing procedures in the field have not yet been estimated without assuming that the PCR constitutes a gold standard test. We use latent class models to estimate the in situ performance of both tests using data from the Danish national registries. We find that the specificity of both tests is very high (>99.7%), while the sensitivities are 95.7% (95% confidence interval CI: 92.8%–98.4%) and 53.8% (95% CI: 49.8%–57.9%) for the PCR and antigen tests, respectively. These findings have implications for the use of confirmatory PCR tests following a positive antigen test result: we estimate that serial testing is counterproductive at higher prevalence levels.
Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales
. However, insights into the population dynamics in the contact zones are hampered by a lack of ...ancient genomic data sampled at high spatiotemporal resolution
. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (
C and
N content), mobility (
Sr/
Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
ObjectivesTo evaluate the feasibility and reliability of hand-held ultrasound (HUD) examinations with real-time automatic decision-making software for ejection fraction (autoEF) and mitral annular ...plane systolic excursion (autoMAPSE) by novices (general practitioners), intermediate users (registered cardiac nurses) and expert users (cardiologists), respectively, compared to reference echocardiography by cardiologists in an outpatient cohort with suspected heart failure (HF).DesignFeasibility study of a diagnostic test.Setting and participants166 patients with suspected HF underwent HUD examinations with autoEF and autoMAPSE measurements by five novices, three intermediate-skilled users and five experts. HUD results were compared with a reference echocardiography by experts. A blinded cardiologist scored all HUD recordings with automatic measurements as (1) discard, (2) accept, but adjust the measurement or (3) accept the measurement as it is.Primary outcome measureThe feasibility of automatic decision-making software for quantification of left ventricular function.ResultsThe users were able to run autoEF and autoMAPSE in most patients. The feasibility for obtaining accepted images (score of ≥2) with automatic measurements ranged from 50% to 91%. The feasibility was lowest for novices and highest for experts for both autoEF and autoMAPSE (p≤0.001). Large coefficients of variation and wide coefficients of repeatability indicate moderate agreement. The corresponding intraclass correlations (ICC) were moderate to good (ICC 0.51–0.85) for intra-rater and poor (ICC 0.35–0.51) for inter-rater analyses. The findings of modest to poor agreement and reliability were not explained by the experience of the users alone.ConclusionNovices, intermediate and expert users were able to record four-chamber views for automatic assessment of autoEF and autoMAPSE using HUD devices. The modest feasibility, agreement and reliability suggest this should not be implemented into clinical practice without further refinement and clinical evaluation.Trial registration numberNCT03547076.
Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. ...These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies.
In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein. Using a specific PLK-2 inhibitor (compound 37), we demonstrate that endogenous PLK-2 phosphorylates S129 only in some cells, but increases α-synuclein protein levels in all tested cell cultures and brain slices. PLK-2 is found to regulate the transcription of α-synuclein mRNA from both the endogenous mouse SNCA gene and transgenic vectors that only contain the open reading frame. Moreover, we are the first to show that regulation of α-synuclein by PLK-2 is of physiological importance since 10days' inhibition of endogenous PLK-2 in wt C57BL/6 mice increases endogenous α-synuclein protein levels.
Our findings collectively demonstrate that PLK-2 regulates α-synuclein levels by a previously undescribed transcription-based mechanism. This mechanism is active in cells and brain tissue, opening up for alternative strategies for modulating α-synuclein levels and thereby for the possibility of modifying disease progression in synucleinopaties.
•Polo-like kinase 2 (PLK-2) inhibition rapidly increases α-synuclein protein levels by increasing α-synuclein mRNA production.•α-synuclein mRNA increase depends on the kinase activity of PLK-2, but not on phosphorylation of S129 on α-synuclein.•PLK-2 activity regulates α-synclein protein levels in vivo.
Ultra-low dose computed tomography (ULD-CT) assessed by non-radiologists in a medical Emergency Department (ED) has not been examined in previous studies. To (i) investigate intragroup agreement ...among attending physicians caring for ED patients (i.e., radiologists, senior- and junior clinicians) and medical students for the detection of acute lung conditions on ULD-CT and supine chest X-ray (sCXR), and (ii) evaluate the accuracy of interpretation compared to the reference standard. In this prospective study, non-traumatic patients presenting to the ED, who received an sCXR were included. Between February and July 2019, 91 patients who underwent 93 consecutive examinations were enrolled. Subsequently, a ULD-CT and non-contrast CT were performed. The ULD-CT and sCXR were assessed by 3 radiologists, 3 senior clinicians, 3 junior clinicians, and 3 medical students for pneumonia, pneumothorax, pleural effusion, and pulmonary edema. The non-contrast CT, assessed by a chest radiologist, was used as the reference standard. The results of the assessments were compared within each group (intragroup agreement) and with the reference standard (accuracy) using kappa statistics. Accuracy and intragroup agreement improved for pneumothorax on ULD-CT compared with the sCXR for all groups. Accuracy and intragroup agreement improved for pneumonia on ULD-CT when assessed by radiologists and for pleural effusion when assessed by medical students. In patients with acute lung conditions ULD-CT offers improvement in the detection of pneumonia by radiologists and the detection of pneumothorax by radiologists as well as non-radiologists compared to sCXR. Therefore, ULD-CT may be considered as an alternative first-line imaging modality to sCXR for non-traumatic patients who present to EDs.
Escapes of domesticated fish from aquaculture, followed by interbreeding with wild conspecifics, represent a threat to the genetic integrity and evolutionary trajectory of natural populations. ...Approximately fifty years of Atlantic salmon production has left an unprecedented legacy of widespread introgression of domesticated escapees in wild Norwegian populations. A major question, however, is whether current aquaculture practice will lead to additional introgression in the near future. As part of the updated Norwegian risk assessment of fish farming, we conducted a risk assessment for further introgression of domesticated escapees in wild populations in Norway. Extensive data of reported numbers of escapees, observed proportions of escapees in rivers, removal of escapees pre‐spawning, and the resilience of wild populations through demographic and genetic status informed the risk assessment. The analysis revealed that rivers in 10 of the 13 aquaculture production zones covering Norway display a moderate or high risk of further introgression of domesticated escapees. This comes in addition to widespread introgression that is already documented. We therefore conclude that so long as aquaculture production continues at its present level and form, there is a moderate‐to‐high risk of further introgression of domesticated salmon in many native populations throughout much of Norway.
PDF
