Cerebrospinal fluid cytokines in Lyme neuroborreliosis

Background: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB.Methods: CSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method.Results: Distinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF.Conclusions: Despite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB

Environment simulator for studying automatic crop farming

Agricultural machines capable of utilizing variable rate application technology are tackling spatial variability in agricultural fields.  Agricultural field robots are the next step in technology, robots which are capable of utilizing sensor and actuating technologies without human contact and operate only areas of interest.  However, agricultural field robots are still under research.  Robots are just one part of the next generation of crop farming having more advanced tools to do the work which currently requires humans.  The next generation of crop farming, in the vision of the authors, is based on automation, which incorporates stationary and moving sensors systems, robots, model based decision making, automated operation planning which adapts to spatial variability according to the measurements as well as to weather conditions.  This article presents a top-down approach of automated crop farming using simulation, trying to cover all the component parts on a fully automated farm.  In the article, the developed simulation platform is presented as well as sample simulation results.  The environment simulator is based on crop growth models, weed growth models, soil models, spatial variation generation and weather statistics.  Models for the environment were found in literature and were tailored and tuned to fit the simulation purposes, to form a collection of models.  The collection of models was evaluated by using sensitivity analysis.  Furthermore, a full scale scenario was simulated over one season, incorporating 9000 spatial cells in five fields of a farm.   Keywords: robots, crop growth models, soil water models, decision making, operation plannin

The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects

Background:Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects. Methods:Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration foreach subject. Results: The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Rα, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-γ-induced protein 10 and monokine induced by IFN-γ, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF. Conclusions:Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms. Trial registration: Before subject enrollment, the study was registered in the European Clinical Trials database(EudraCT number 2013–001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013).</p

Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness

Background: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery.Methods: Healthy participants received dexmedetomidine (n = 23) or propofol (n = 24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed.Results: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously.Conclusion: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness.</p

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes.</p

Soluble CD73 in Critically Ill Septic Patients Data from the Prospective FINNAKI Study

Background CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality. Methods This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012. Plasma samples of 588 patients admitted with severe sepsis/shock or with developing severe sepsis were analyzed at 0h (ICU admission) and 24h, and additionally, on day 3 or day 5 from a subset of the patients. Results The median [IQR] sCD73 levels at 0h were 5.11 [3.29-8.28] ng/mL and they decreased significantly from 0h to 4.14 [2.88-7.11] ng/mL at 24h, P Conclusions Compared to normal population, the sCD73 levels were generally low at 0h, showed a decrease to 24h, and later an increase by day 5. The sCD73 levels do not seem useful in predicting the development of AKI or 90-day mortality among patients with severe sepsis or shock.Peer reviewe

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study

Introduction: The highly selective alpha(2)-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses.Methods: One hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml (1); n=40), propofol (1.7 mu g ml (1); n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 mu g ml (1); n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. F-18-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions.Results: At the time of [F-18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (PConclusions: At equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia.</p

The incidence of unpleasant dreams after sub-anaesthetic ketamine

Ketamine is an N-methyl-D-aspartate (NMDA)receptor antagonist with psychotogenic effects and for whichthere are diverse reports of whether pleasant or unpleasantdreams result during anaesthesia, post-operatively or aftersub-anaesthetic use. The aim was to assess in healthy volunteers the incidence ofunpleasant dreams over the three nights after receiving asub-anaesthetic dose of ketamine, in comparison to placebo,and with retrospective home nightmare frequency as acovariate.Thirty healthy volunteers completed questionnairesabout retrospective home dream recall and were then giveneither ketamine or placebo. Ketamine resulted in significantly more meandream unpleasantness relative to placebo and caused athreefold increase in the odds ratio for the incidence of anunpleasant dream. The number of dreams reported over thethree nights did not differ between the groups. Theincidence of unpleasant dreams after ketamine use waspredicted by retrospectively assessed nightmare frequencyat home.Ketamine causes unpleasant dreams over thethree post-administration nights. This may be evidence of aresidual psychotogenic effect that is not found on standardself-report symptomatology measures or a result of disturbedsleep electrophysiology. The results have theoretical implications for the relationship between nightmares and schizotypy

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease

Objective This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.Methods BMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI-driven cytokines on risk of obesity-related diseases. Results Observationally, BMI was associated with 19 cytokines. For every SD increase in BMI, causal effect estimates were strongest for hepatocyte growth factor, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and were as ratios of geometric means 1.13 (95% CI: 1.08-1.19), 1.08 (95% CI: 1.04-1.14), and 1.13 (95% CI: 1.04-1.21), respectively. TRAIL was associated with a small increase in the odds of coronary artery disease (odds ratio: 1.03; 95% CI: 1.00-1.06). There was inconsistent evidence for a protective role of MCP-1 against inflammatory bowel diseases.Conclusions Observational and MR estimates of the effect of BMI on cytokine levels were generally concordant. There was little evidence for an effect of raised levels of BMI-driven cytokines on disease. These findings illustrate the challenges of MR when applied in the context of molecular mediation.</p