| 11. |
- Gifford, Robert, et al.
(författare)
-
Temporal pessimism and spatial optimism in environmental assessments: An 18-nation study
- 2009
-
Ingår i: Journal of Environmental Psychology. - : Elsevier BV. - 0272-4944. ; 29, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- The personal assessments of the current and expected future state of the environment by 3232 community respondents in 18 nations were investigated at the local, national, and global spatial levels. These assessments were compared to a ranking of each country's environmental quality by an expert panel. Temporal pessimism (“things will get worse”) was found in the assessments at all three spatial levels. Spatial optimism bias (“things are better here than there”) was found in the assessments of current environmental conditions in 15 of 18 countries, but not in the assessments of the future. All countries except one exhibited temporal pessimism, but significant differences between them were common. Evaluations of current environmental conditions also differed by country. Citizens' assessments of current conditions, and the degree of comparative optimism, were strongly correlated with the expert panel's assessments of national environmental quality. Aside from the value of understanding global trends in environmental assessments, the results have important implications for environmental policy and risk management strategies.
|
|
| 12. |
- Kasri, Amal, et al.
(författare)
-
Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer's disease with APPdup and Down syndrome
- 2024
-
Ingår i: ACTA NEUROPATHOLOGICA. - 0001-6322 .- 1432-0533. ; 148:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is characterized by extracellular amyloid plaques containing amyloid-beta (A beta) peptides, intraneuronal neurofibrillary tangles, extracellular neuropil threads, and dystrophic neurites surrounding plaques composed of hyperphosphorylated tau protein (pTau). A beta can also deposit in blood vessel walls leading to cerebral amyloid angiopathy (CAA). While amyloid plaques in AD brains are constant, CAA varies among cases. The study focuses on differences observed between rare and poorly studied patient groups with APP duplications (APPdup) and Down syndrome (DS) reported to have higher frequencies of elevated CAA levels in comparison to sporadic AD (sAD), most of APP mutations, and controls. We compared A beta and tau pathologies in postmortem brain tissues across cases and A beta peptides using mass spectrometry (MS). We further characterized the spatial distribution of A beta peptides with MS-brain imaging. While intraparenchymal A beta deposits were numerous in sAD, DS with AD (DS-AD) and AD with APP mutations, these were less abundant in APPdup. On the contrary, A beta deposits in the blood vessels were abundant in APPdup and DS-AD while only APPdup cases displayed high A beta deposits in capillaries. Investigation of A beta peptide profiles showed a specific increase in A beta x-37, A beta x-38 and A beta x-40 but not A beta x-42 in APPdup cases and to a lower extent in DS-AD cases. Interestingly, N-truncated A beta 2-x peptides were particularly increased in APPdup compared to all other groups. This result was confirmed by MS-imaging of leptomeningeal and parenchymal vessels from an APPdup case, suggesting that CAA is associated with accumulation of shorter A beta peptides truncated both at N- and C-termini in blood vessels. Altogether, this study identified striking differences in the localization and composition of A beta deposits between AD cases, particularly APPdup and DS-AD, both carrying three genomic copies of the APP gene. Detection of specific A beta peptides in CSF or plasma of these patients could improve the diagnosis of CAA and their inclusion in anti-amyloid immunotherapy treatments.
|
|
| 13. |
- Kervarrec, Thibault, et al.
(författare)
-
Merkel Cell Polyomavirus‒Negative Merkel Cell Carcinoma Originating from In Situ Squamous Cell Carcinoma : A Keratinocytic Tumor with Neuroendocrine Differentiation
- 2022
-
Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X. ; 142:3, s. 516-527
-
Tidskriftsartikel (refereegranskat)abstract
- Although virus-negative Merkel cell carcinoma (MCC) is characterized by a high frequency of UV-induced mutations, the expression of two viral oncoproteins is regarded as a key mechanism driving Merkel cell polyomavirus‒positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC), suggesting (i) coincidental collision, (ii) one providing a niche for the other, or (iii) one evolving from the other. Whole-exome sequencing of four combined tumors consisting of SCC in situ and Merkel cell polyomavirus‒negative MCC showed many mutations shared between SCC and MCC in all cases, indicating a common ancestry and thereby a keratinocytic origin of these MCCs. Moreover, analyses of the combined cases as well as of pure SCC and MCC suggest that RB1 inactivation in SCC facilitates MCC development and that epigenetic changes may contribute to the SCC/MCC transition.
|
|
| 14. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 15. |
- Kowal-Bielecka, Otylia, et al.
(författare)
-
Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
|
|
| 16. |
- Kremer, Christine, et al.
(författare)
-
European Stroke Organisation guidelines on stroke in women : Management of menopause, pregnancy and postpartum
- 2022
-
Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- Pregnancy, postpartum and menopause are regarded as periods women are more vulnerable to ischaemic events. There are conflicting results regarding stroke risk and hormone replacement therapy (HRT) during menopause. Stroke in pregnancy is generally increasing with serious consequences for mother and child; therefore, recommendations for acute treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) are needed. The aim of this guideline is to support and guide clinicians in treatment decisions in stroke in women. Following the “Grading of Recommendations and Assessment, Development and Evaluation (GRADE)” approach, the guidelines were developed according to the European Stroke Organisation (ESO) Standard Operating Procedure. Systematic reviews and metanalyses were performed. Based on available evidence, recommendations were provided. Where there was a lack of evidence, an expert consensus statement was given. Low quality of evidence was found to suggest against the use of HRT to reduce the risk of stroke (ischaemic and haemorrhagic) in postmenopausal women. No data was available on the outcome of women with stroke when treated with HRT. No sufficient evidence was found to provide recommendations for treatment with IVT or MT during pregnancy, postpartum and menstruation. The majority of members suggested that pregnant women can be treated with IVT after assessing the benefit/risk profile on an individual basis, all members suggested treatment with IVT during postpartum and menstruation. All members suggested treatment with MT during pregnancy. The guidelines highlight the need to identify evidence for stroke prevention and acute treatment in women in more vulnerable periods of their lifetime to generate reliable data for future guidelines.
|
|
| 17. |
- Kremer, Christine, et al.
(författare)
-
Sex differences in Outcome after Carotid Revascularization in Symptomatic and Asymptomatic Carotid Artery Stenosis
- 2023
-
Ingår i: Journal of Vascular Surgery. - 1097-6809. ; 78:3, s. 10-827
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveSex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials leading to limited conclusions regarding the safety and efficacy of acute stroke treatments.MethodsA systematic review and meta-analysis was performed by literature search including 4 databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed.ResultsRegarding carotid endarterectomy (CEA) in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (p=0.16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565; 7.2% vs 5.0%; OR 1.49, 95% CI 1.04-2.12; I2=0%; p=0.03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs. 6.7%; OR 2.81,95% CI 1.66-4.75; p=0.0001). For carotid stenting (CAS) in symptomatic artery stenosis data showed a non-significant tendency toward higher peri-procedural stroke in women. Whereas, for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women compared to men after CEA had similar rates of stroke, stroke or death and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared to men (1 study, 372 patients; 10.8% vs 3.2%; OR 3.71, 95% CI 1.49-9.2; p=0.005).Furthermore, carotid stenting in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs. 0.6%, OR 2.01, 95%CI 1.23-3.28, I2=0%, p=0.005).ConclusionsA few sex-differences in short term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in RCTs, to better understand if sex differences exist and to tailor carotid revascularization accordingly.
|
|
| 18. |
- Lepri, Gemma, et al.
(författare)
-
Systemic sclerosis and primary biliary cholangitis : Longitudinal data to determine the outcomes
- 2023
-
Ingår i: Journal of Scleroderma and Related Disorders. - 2397-1983. ; 8:3, s. 210-220
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis–primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis–specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis–systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis–primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies (p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis–systemic sclerosis patients (p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension (p < 0.001) and of conduction blocks (p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. Conclusion: Our data show that systemic sclerosis–primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.
|
|
| 19. |
|
|
| 20. |
- Mastropasqua, Francesca, et al.
(författare)
-
Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis.
- 2023
-
Ingår i: Biology open. - : The Company of Biologists. - 2046-6390. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level HNRNPU downregulation leads to an increased fraction of neural progenitors in the maturing neuronal population. We conclude that the HNRNPU locus is involved in delayed commitment of neural progenitors to differentiate in cell types with hindbrain profile.
|
|
