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- Maasri, Alain, et al.
(author)
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A global agenda for advancing freshwater biodiversity research
- 2022
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 255-263
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Journal article (peer-reviewed)abstract
- Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.
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- Douna, H, et al.
(author)
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IFNγ-Stimulated B Cells Inhibit T Follicular Helper Cells and Protect Against Atherosclerosis
- 2022
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In: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 9, s. 781436-
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Journal article (peer-reviewed)abstract
- B and T cells are interconnected in the T follicular helper—germinal center B cell (TFH-GC B cell) axis, which is hyperactive during atherosclerosis development and loss of control along this axis results in exacerbated atherosclerosis. Inhibition of the TFH–GC B cell axis can be achieved by providing negative co-stimulation to TFH cells through the PD-1/PD-L1 pathway. Therefore, we investigated a novel therapeutic strategy using PD-L1-expressing B cells to inhibit atherosclerosis. We found that IFNγ-stimulated B cells significantly enhanced PD-L1 expression and limited TFH cell development. To determine whether IFNγ-B cells can reduce collar-induced atherosclerosis, apoE−/− mice fed a Western-type diet were treated with PBS, B cells or IFNγ-B cells for a total of 5 weeks following collar placement. IFNγ-B cells significantly increased PD-L1hi GC B cells and reduced plasmablasts. Interestingly, IFNγ-B cells–treated mice show increased atheroprotective Tregs and T cell-derived IL-10. In line with these findings, we observed a significant reduction in total lesion volume in carotid arteries of IFNγ-B cells-treated mice compared to PBS-treated mice and a similar trend was observed compared to B cell-treated mice. In conclusion, our data show that IFNγ-stimulated B cells strongly upregulate PD-L1, inhibit TFH cell responses and protect against atherosclerosis.
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- Kuiper, I. N., et al.
(author)
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Associations of Preconception Exposure to Air Pollution and Greenness with Offspring Asthma and Hay Fever
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 17:16
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Journal article (peer-reviewed)abstract
- We investigated if greenness and air pollution exposure in parents' childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM(2.5)and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O-3) (mu g/m(3)) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0-18 years old and offspring 0-10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM(2.5)and PM(10)exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32-3.78, OR 2.27, 95%CI 1.36-3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11-0.87). Hay fever risk increased for offspring of fathers with medium O(3)exposure (OR 4.15, 95%CI 1.28-13.50) and mothers with high PM(10)exposure (OR 2.66, 95%CI 1.19-5.91). The effect of maternal PM(10)exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring's own exposures. Paternal O(3)exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.
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- Lagebrant, Alice, et al.
(author)
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Brain injury markers in blood associate with generalised oedema on computed tomography after cardiac arrest
- 2021
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In: - : Springer Science and Business Media LLC. ; , s. 203-204
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Conference paper (peer-reviewed)abstract
- Introduction. According to the 2021 ERC/ESICM guideline recommen-dations, elevated neuron-specific enolase [NSE] levels as well as diffuseand extensive anoxic damage on neuroimaging are predictors of poorneurological outcome after cardiac arrest.(1) We previously describedthat NSE is elevated in patients with generalised oedema on com-puted tomography [CT]. (2).Objectives. In this study, we aim to examine the novel brain injurymarkers serum neurofilament light [NFL], glial fibrillary acidic protein[GFAP] and total-tau [tau] to predict the presence of generalised brainoedema.Methods. Retrospective analysis of patients examined with CT onclinical indication within the Target Temperature Management afterout-of-hospital cardiac arrest [TTM] trial. (2,3) Serum samples fromthe biobank sub study were prospectively collected at 48 h post arrestand analysed after trial completion as published. (4–7) The neuronalmarker NSE, the neuroaxonal injury markers NFL and tau and theastrocytic injury marker GFAP were correlated with the presence ofgeneralised oedema on CT, assessed by local radiologists through vis-ual evaluation. The prognostic accuracy of NSE ≥ 60 ug/l for predictinggeneralised oedema was also analysed.Results. 192 patients had data available on all four biomarkers at 48 hand were examined with CT < 168 h post arrest. Brain injury markerswere significantly higher in patients with generalised oedema as com-pared to patients without oedema on CT scans performed 24–168 hafter ROSC (p < 0.001) (Fig. 1A–D). For CT scans performed < 24 h, onlyNSE levels showed a significant correlation (p < 0.05). Biomarkers pre -dicted generalised oedema with area under the receiver operatingcharacteristics curve [AUC] 67.5–73.2% for CT scans performed < 24 h(n = 111), with no statistically significant difference between themarkers ( Fig. 2A). For scans performed 24–168 h (n = 81) AUC for pre -dicting generalised oedema was 78.1%-82.9%, with no statisticallysignificant difference between the markers. NSE ≥ 60 ug/l at 48 h, asrecommended by guidelines, predicted generalised oedema with 81%(95%CI 67–90%) sensitivity and 77% (95%CI 62–87%) specificity.Conclusion. Concentrations of all evaluated brain injury markerswere significantly higher in patients with generalised oedema on CTperformed after the first 24 h post arrest. Biomarker concentrationsindicate whether generalised oedema on CT is likely and may thus beclinically useful for deciding if a CT scan is sufficient for prognostica-tion or if a MRI is more appropriate.
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- Lu, Chang, et al.
(author)
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Identification of a gene network driving the attenuated response to lipopolysaccharide of monocytes from hypertensive coronary artery disease patients
- 2024
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 15
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Journal article (peer-reviewed)abstract
- Introduction: The impact of cardiovascular disease (CVD) risk factors, encompassing various biological determinants and unhealthy lifestyles, on the functional dynamics of circulating monocytes—a pivotal cell type in CVD pathophysiology remains elusive. In this study, we aimed to elucidate the influence of CVD risk factors on monocyte transcriptional responses to an infectious stimulus. Methods: We conducted a comparative analysis of monocyte gene expression profiles from the CTMM – CIRCULATING CELLS Cohort of coronary artery disease (CAD) patients, at baseline and after lipopolysaccharide (LPS) stimulation. Gene co-expression analysis was used to identify gene modules and their correlations with CVD risk factors, while pivotal transcription factors controlling the hub genes in these modules were identified by regulatory network analyses. The identified gene module was subjected to a drug repurposing screen, utilizing the LINCS L1000 database. Results: Monocyte responsiveness to LPS showed a highly significant, negative correlation with blood pressure levels (ρ< -0.4; P<10-80). We identified a ZNF12/ZBTB43-driven gene module closely linked to diastolic blood pressure, suggesting that monocyte responses to infectious stimuli, such as LPS, are attenuated in CAD patients with elevated diastolic blood pressure. This attenuation appears associated with a dampening of the LPS-induced suppression of oxidative phosphorylation. Finally, we identified the serine-threonine inhibitor MW-STK33-97 as a drug candidate capable of reversing this aberrant LPS response. Conclusions: Monocyte responses to infectious stimuli may be hampered in CAD patients with high diastolic blood pressure and this attenuated inflammatory response may be reversed by the serine-threonine inhibitor MW-STK33-97. Whether the identified gene module is a mere indicator of, or causal factor in diastolic blood pressure and the associated dampened LPS responses remains to be determined.
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- Raymond, Christopher, et al.
(author)
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Inclusive conservation and the Post-2020 Global Biodiversity Framework : Tensions and prospects
- 2022
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In: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:3, s. 252-264
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Journal article (peer-reviewed)abstract
- The draft Post-2020 Global Biodiversity Framework commits to achievement of equity and justice outcomes and represents a “relational turn” in how we understand inclusive conservation. Although “inclusivity” is drawn on as a means to engage diverse stakeholders, widening the framing of inclusivity can create new tensions with regard to how to manage protected areas. We first offer a set of tensions that emerge in the light of the relational turn in biodiversity conservation. Drawing on global case examples applying multiple methods of inclusive conservation, we then demonstrate that, by actively engaging in the interdependent phases of recognizing hybridity, enabling conditions for reflexivity and partnership building, tensions can not only be acknowledged but softened and, in some cases, reframed when managing for biodiversity, equity, and justice goals. The results can improve stakeholder engagement in protected area management, ultimately supporting better implementation of global biodiversity targets.
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- Timmers, Elze R., et al.
(author)
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Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients
- 2021
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In: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 91, s. 48-54
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Journal article (peer-reviewed)abstract
- Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = −0.3, p < 0.01), depression (rs = −0.3, p < 0.01) and fatigue (rs = −0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.
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| 10. |
- Frantzen, Astri Tafjord, et al.
(author)
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Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement
- 2021
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In: Heart, Lung and Circulation. - : Elsevier. - 1443-9506 .- 1444-2892. ; 30:8, s. 1221-1231
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Journal article (peer-reviewed)abstract
- BackgroundFrailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care.AimWe aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR.MethodIn a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated.ResultsData were available for 143 consecutive patients (mean age 83 +/- 2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002).ConclusionsAdvanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.
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