| 1. |
- Abbey-Lee, Robin, et al.
(författare)
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Experimental manipulation of monoamine levels alters personality in crickets
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Animal personality has been described in a range of species with ecological and evolutionary consequences. Factors shaping and maintaining variation in personality are not fully understood, but monoaminergic systems are consistently linked to personality variation. We experimentally explored how personality was influenced by alterations in two key monoamine systems: dopamine and serotonin. This was done using ropinirole and fluoxetine, two common human pharmaceuticals. Using the Mediterranean field cricket (Gryllus bimaculatus), we focused on the personality traits activity, exploration, and aggression, with confirmed repeatability in our study. Dopamine manipulations explained little variation in the personality traits investigated, while serotonin manipulation reduced both activity and aggression. Due to limited previous research, we created a dose-response curve for ropinirole, ranging from concentrations measured in surface waters to human therapeutic doses. No ropinirole dose level strongly influenced cricket personality, suggesting our results did not come from a dose mismatch. Our results indicate that the serotonergic system explains more variation in personality than manipulations of the dopaminergic system. Additionally, they suggest that monoamine systems differ across taxa, and confirm the importance of the mode of action of pharmaceuticals in determining their effects on behaviour.
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| 2. |
- Brundin, L., et al.
(författare)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 3. |
- Forsström, David, 1981-, et al.
(författare)
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Isolation and worry in relation to gambling and onset of gambling among psychiatry patients during the COVID-19 pandemic : A mediation study
- 2022
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- When the COVID-19 pandemic started spreading globally, there was a fear that addictive behaviors would increase due to changes in everyday life caused by restrictions due to COVID-19. Studies were carried out to explore if this was true for gambling, typically revealing no overall increase in gambling behavior, although individuals who had previous experience with gambling problems were more likely to increase gambling during the pandemic. However, these studies only included individuals with previous gambling problems. It remains unknown whether other vulnerable groups, such as individuals with common mental disorders increased their gambling. This study aimed to explore the level of gambling problems among individuals with a history of mental disorders, namely, (i) pre-pandemic gamblers and (ii) pandemic-onset gamblers. Furthermore, we explored if worry and isolation mediate gambling and problem gambling. The data were analyzed using descriptive statistics and a structural equation model to investigate mediation. The results showed a high prevalence of at-risk and problem gambling in both groups. The pre-pandemic gamblers had a high level of at-risk and problem gambling. Furthermore, the individuals that started to gamble during the pandemic had an even higher degree of at-risk and problem gambling. The mediation showed that the onset of gambling was linked with the worry of COVID-infection and that worry predicted the level of gambling problems. This study highlights that vulnerability factors, isolation, and worry can be triggers for individuals with common mental disorders to engage in gambling as well as the importance of screening this population for gambling problems.
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| 4. |
- Herlitz, Johan, 1949-, et al.
(författare)
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Över 100 doktorsavhandlingar inom den prehospitala akutsjukvården i Sverige
- 2023
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 1652-7518. ; 120
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Forskningsöversikt (refereegranskat)abstract
- HUVUDBUDSKAPÖver 100 avhandlingar har i dagsläget skrivits om den prehospitala akutsjukvården i Sverige.Dessa täcker ett omfattande kunskapsfält, allt ifrån prognostiska faktorer vid akut sjukdom till ambulans personalens psykiska och fysiska hälsa.Endast ett kunskapsområde har belysts mera om fattande, och det är hjärt–lungräddning vid plötsligt hjärtstopp.Vården av patienter med psykisk ohälsa har inte belysts i någon avhandling.Det finns stora kunskapsluckor, och vidare forskning inom området behövs.
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| 5. |
- Jiang, Hao, et al.
(författare)
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Protonation of Homocitrate and the E1 State of Fe-Nitrogenase Studied by QM/MM Calculations
- 2023
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Ingår i: Inorganic Chemistry. - 1520-510X. ; 62:48, s. 19433-19445
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Tidskriftsartikel (refereegranskat)abstract
- Nitrogenase is the only enzyme that can cleave the strong triple bond in N2, making nitrogen available for biological life. There are three isozymes of nitrogenase, differing in the composition of the active site, viz., Mo, V, and Fe-nitrogenase. Recently, the first crystal structure of Fe-nitrogenase was presented. We have performed the first combined quantum mechanical and molecular mechanical (QM/MM) study of Fe-nitrogenase. We show with QM/MM and quantum-refinement calculations that the homocitrate ligand is most likely protonated on the alcohol oxygen in the resting E0 state. The most stable broken-symmetry (BS) states are the same as for Mo-nitrogenase, i.e., the three Noodleman BS7-type states (with a surplus of β spin on the eighth Fe ion), which maximize the number of nearby antiferromagnetically coupled Fe–Fe pairs. For the E1 state, we find that protonation of the S2B μ2 belt sulfide ion is most favorable, 14–117 kJ/mol more stable than structures with a Fe-bound hydride ion (the best has a hydride ion on the Fe2 ion) calculated with four different density-functional theory methods. This is similar to what was found for Mo-nitrogenase, but it does not explain the recent EPR observation that the E1 state of Fe-nitrogenase should contain a photolyzable hydride ion. For the E1 state, many BS states are close in energy, and the preferred BS state differs depending on the position of the extra proton and which density functional is used.
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| 6. |
- Kjellman, Christian, et al.
(författare)
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Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier. - 1600-6135 .- 1600-6143. ; 21:12, s. 3907-3918
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Tidskriftsartikel (refereegranskat)abstract
- Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation.
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| 7. |
- Labori, Knut Jørgen, et al.
(författare)
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Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial
- 2024
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Ingår i: The Lancet Gastroenterology & Hepatology. - : The Lancet Group. - 2468-1253. ; 9:3, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.MethodsNORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.FindingsBetween Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.InterpretationThis phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
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| 8. |
- Lundgren, Kristoffer, et al.
(författare)
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Increased dietary 5-hydroxytryptophan reduces fearfulness in red junglefowl hens (Gallus gallus)
- 2023
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Ingår i: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Our production animals typically suffer poor welfare, which can be revealed by measuring the affective state these animals are in. Negative affective state is linked to poorer welfare, and can be measured as fearfulness. While continuing to research how to improve animal welfare, a compliment to reduce negative affective state could therefore be to reduce individuals fearfulness, similar to how negative affective states are medicated in humans. A proposed mechanism for this is via the monoaminergic systems. This is based on previous studies across species that have linked the serotonergic system and fear-related behaviour. We here aimed to experimentally manipulate the serotonergic system in red junglefowl hens (Gallus gallus), the main ancestor of all domesticated chickens. We measured fearfulness as latency remaining immobile in a tonic immobility test, and did so both before and after our experimental manipulation. We set out to experimentally manipulate the serotonergic system via sub-chronic dietary treatment of 5-hydroxytryptophan (the precursor to serotonin). Our dietary manipulation of 5-hydroxytryptophan significantly reduced measured fearfulness in the manipulated hens, while latency in tonic immobility did not significantly change in our unmanipulated, control hens. This finding is promising since it indicates that increased tryptophan levels can be used to reduce fearfulness. Additionally, our result suggests that this can be done non-invasively via food (instead of injections), thus presenting a potentially feasible manipulation also for larger settings. Nevertheless, the serotonergic system is complex and its role in modulating behaviour in the fowl should be explored further to evaluate our findings, and more directly explored also in a production setting.
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| 9. |
- Lundgren, Kristoffer, et al.
(författare)
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Manipulating monoamines reduces exploration and boldness of Mediterranean field crickets
- 2021
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Ingår i: Behavioural Processes. - : Elsevier. - 0376-6357 .- 1872-8308. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- Despite the prevalence and research interest of animal personality, its underlying mechanisms are not yet fully understood. Due to the essential role of monoamines in modulating behaviour, we manipulated the monoaminergic systems of Mediterranean field crickets (Gryllus bimaculatus) to explore whether this altered behavioural responses commonly used to describe animal personality. Previous work has shown that both serotonin and dopamine manipulations can alter cricket behaviour, although results differ depending on the drug in focus. Here, we investigate the effect of Fluphenazine, a dopamine antagonist which also interacts with serotonin receptors, on activity, exploration, boldness, and aggression. These results are compared with those of our earlier work that investigated the effect of drugs that more specifically target serotonin or dopamine systems (Fluoxetine and Ropinirole, respectively). Due to limited research on dose-effects of Fluphenazine, we created dose-response curves with concentrations ranging from those measured in surface waters up to human therapeutic doses. We show that compared to control animals, Fluphenazine manipulation resulted in lower levels of both exploration and boldness, but did not affect activity nor aggression. The effect on explorative behaviour contradicts our previous results of serotonin and dopamine manipulations. These results together confirm the causal role of monoamines in explaining variation in behaviour often used to describe animal personality, effects that can be both doseand behaviour-dependent. Further, our results suggest that previous results assigned specifically to the dopaminergic system, may at least partly be explained by effects of the serotonergic system. Thus, future studies should continue to investigate the explicit underlying roles of specific monoamines in explaining behavioural variation.
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| 10. |
- Rasmussen, Morten K., et al.
(författare)
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Stable Cation Inversion at the MgAl2O4(100) Surface
- 2011
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Ingår i: Physical Review Letters. - 1079-7114. ; 107:3
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Tidskriftsartikel (refereegranskat)abstract
- From an interplay of atom-resolved noncontact atomic force microscopy, surface x-ray diffraction experiments, and density functional theory calculations, we reveal the detailed atomic-scale structure of the (100) surface of an insulating ternary metal oxide, MgAl2O4 (spinel). We surprisingly find that the MgAl2O4(100) surface is terminated by an Al and O-rich structure with a thermodynamically favored amount of Al atoms interchanged with Mg. This finding implies that so-called Mg-Al antisites, which are defects in the bulk of MgAl2O4, become a thermodynamically stable and integral part of the surface.
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| 11. |
- Rozental, Alexander, 1985-, et al.
(författare)
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Mental health in individuals with self-reported psychiatric symptoms during the COVID-19 pandemic : Baseline data from a swedish longitudinal cohort study
- 2022
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Individuals with psychiatric disorders may be both vulnerable and sensitive to rapid societal changes that have occurred during the COVID-19 pandemic. To fully understand these impacts, repeated measurements of these individuals are warranted. The current longitudinal study set out to perform monthly assessment of individuals with common psychiatric disorders using established questionnaires with a possibility for them to self- rate their symptoms, over time.Methods: Recruitment of individuals who identified themselves as struggling with mental health problems, living in Sweden between July 2020 and June 2021 using an online survey. The individuals answered questions on demographics, psychiatric history, current psychiatric symptoms (e.g., Patient Health Questionnaire, PHQ-9; General Anxiety Disorder, GAD-7), somatic health, health-care contacts and any changes therein during the pandemic. Monthly, longitudinal assessments are still ongoing (consenting participants provide data for 1 year), and here we present descriptive statistics from the baseline measurement. All measurements from baseline (>400 items), and follow-ups are presented in detail.Results: A total of 6.095 participants (average age 35 years) submitted complete baseline data. Marital status (43% single) and number of years of education (48% highest degree being high school) were evenly distributed in this population. The most common lifetime psychiatric disorder in the sample was depressive disorder (80.5%) and generalized anxiety disorder (45.9%), with a substantial proportion having severe symptoms of depression. (30.5%) and anxiety (37.1%). Lifetime suicidal ideation (75.0%) and non-suicidal self-harm (57.7%) were prevalent in the group and 14.5% reported drug use during the pandemic. Allergies (36.8%) were the most common somatic condition, followed by irritable bowel syndrome (18.7%). For those having experienced a traumatic event, 39% showed symptoms during the pandemic indicating PTSD. Regarding contact with mental health services during the pandemic, 22% had established a new contact, and 20% reported to have increased their psychiatric medication compared to before the pandemic.Conclusion: Baseline data collected during the pandemic from individuals in Sweden with pre-existing psychiatric disorders demonstrate that this sample represents a population suitable for an investigation on the long-term impact of the pandemic, as intended by the longitudinal investigation that is ongoing. Follow-up questionnaires over a 12-month period are being collected and will indicate how the health and well-being of this population was impacted during the changes and uncertainties that have been characteristic of the past 2 years.
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| 12. |
- Rulisek, Lubomir, et al.
(författare)
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The reaction mechanism of iron and manganese superoxide dismutases studied by theoretical calculations
- 2006
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 1096-987X .- 0192-8651. ; 27:12, s. 1398-1414
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the detailed reaction mechanism of iron and manganese superoxide dismutase with density functional calculations on realistic active-site models, with large basis sets and including solvation, zero-point, and thermal effects. The results indicate that the conversion of O-2(-) to O-2 follows an associative mechanism, with O-2 directly binding to the metal, followed by the protonation of the metal-bound hydroxide ion, and the dissociation of O-3(2). All these reaction steps are exergonic. Likewise, we suggest that the conversion of O-2(-) to H2O2 follows an at least a partly second-sphere pathway. There are small differences in the preferred oxidation and spin states, as well as in the geometries, of Fe and Mn, but these differences have little influence on the energetics, and therefore on the reaction mechanism of the two types of superoxide dismutases. For example, the two metals have very similar reduction potentials in the active-site models, although they differ by 0.7 V in water solution. The reaction mechanisms and spin states seem to have been designed to avoid spin conversions or to facilitate them by employing nearly degenerate spin states. (c) 2006 Wiley Periodicals, Inc.
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| 13. |
- Tegner, Cecilia, et al.
(författare)
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Alpha-chloralose poisoning in cats : clinical findings in 25 confirmed and 78 suspected cases
- 2022
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Ingår i: Journal of feline medicine and surgery. - : SAGE Publications. - 1098-612X .- 1532-2750. ; 24:10, s. E324-E329
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia.
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| 14. |
- Wibring, Kristoffer, et al.
(författare)
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Towards definitions of time-sensitive conditions in prehospital care
- 2020
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Prehospital care has changed in recent decades. Advanced assessments and decisions are made early in the care chain. Patient assessments form the basis of a decision relating to prehospital treatment and the level of care. This development imposes heavy demands on the ability of emergency medical service (EMS) clinicians properly to assess the patient. EMS clinicians have a number of assessment instruments and triage systems available to support their decisions. Many of these instruments are based on vital signs and can sometimes miss time-sensitive conditions. With this commentary, we would like to start a discussion to agree on definitions of temporal states in the prehospital setting and ways of recognising patients with time-sensitive conditions in the most optimal way.MAIN BODY:There are several articles discussing the identification and management of time-sensitive conditions. In these articles, neither definitions nor terminology have been uniform. There are a number of problems associated with the definition of time-sensitive conditions. For example, intoxication can be minor but also life threatening, depending on the type of poison and dose. Similarly, diseases like stroke and myocardial infarction can differ markedly in terms of severity and the risk of life-threatening complications. Another problem is how to support EMS clinicians in the early recognition of these conditions. It is well known that many of them can present without a deviation from normal in vital signs. It will most probably be impossible to introduce specific decision support tools for every individual time-sensitive condition. However, there may be information in the type and intensity of the symptoms patients present. In future, biochemical markers and machine learning support tools may help to identify patients with time-sensitive conditions and predict mortality at an earlier stage.CONCLUSION:It may be of great value for prehospital clinicians to be able to describe time-sensitive conditions. Today, neither definitions nor terminology are uniform. Our hope is that this commentary will initiate a discussion on the issue aiming at definitions of time-sensitive conditions in prehospital care and how they should be recognised in the most optimal fashion.
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| 15. |
- Windahl, Ulrika, et al.
(författare)
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Alpha-chloralose poisoning in cats in three Nordic countries-the importance of secondary poisoning
- 2022
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Ingår i: BMC Veterinary Research. - : Springer Nature. - 1746-6148. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. Methods Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. Results In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. Conclusions Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways.
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| 16. |
- Windahl, Ulrika, et al.
(författare)
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Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning
- 2022
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 46:6, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats.
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