| 1. |
- Birtele, Marcella, et al.
(författare)
-
Dual modulation of neuron-specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons
- 2019
-
Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:23, s. 3370-3380
-
Tidskriftsartikel (refereegranskat)abstract
- Direct neuronal reprogramming can be achieved using different approaches: by expressing neuronal transcription factors or microRNAs; and by knocking down neuronal repressive elements. However, there still exists a high variability in terms of the quality and maturity of the induced neurons obtained, depending on the reprogramming strategy employed. Here, we evaluate different long-term culture conditions and study the effect of expressing the neuronal-specific microRNAs, miR124 and miR9/9*, while reprogramming with forced expression of the transcription factors Ascl1, Brn2, and knockdown of the neuronal repressor REST. We show that the addition of microRNAs supports neuronal maturation in terms of gene and protein expression, as well as in terms of electrophysiological properties.
|
|
| 2. |
- Drouin-Ouellet, Janelle, et al.
(författare)
-
Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson's disease
- 2022
-
Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 17:10, s. 2203-2219
-
Tidskriftsartikel (refereegranskat)abstract
- We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors. Furthermore, stress-induced autophagy resulted in an age-dependent accumulation of macroautophagic structures. Finally, we show that these impairments in patient-derived DA neurons leads to an accumulation of phosphorylated alpha-synuclein, the classical hallmark of PD pathology. This pathological phenotype is absent in neurons generated from induced pluripotent stem cells from the same patients. Taken together, our results show that direct neural reprogramming can be used for obtaining patient-derived DA neurons, which uniquely function as a cellular model to study age-related pathology relevant to idiopathic PD.
|
|
| 3. |
- Jung, Christian, et al.
(författare)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
|
|
| 4. |
- Neri, Emanuele, et al.
(författare)
-
The second ESGAR consensus statement on CT colonography.
- 2013
-
Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 23:3, s. 720-729
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To update quality standards for CT colonography based on consensus among opinion leaders within the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). MATERIAL AND METHODS: A multinational European panel of nine members of the ESGAR CT colonography Working Group (representing six EU countries) used a modified Delphi process to rate their level of agreement on a variety of statements pertaining to the acquisition, interpretation and implementation of CT colonography. Four Delphi rounds were conducted, each at 2months interval. RESULTS: The panel elaborated 86 statements. In the final round the panelists achieved complete consensus in 71 of 86 statements (82%). Categories including the highest proportion of statements with excellent Cronbach's internal reliability were colon distension, scan parameters, use of intravenous contrast agents, general guidelines on patient preparation, role of CAD and lesion measurement. Lower internal reliability was achieved for the use of a rectal tube, spasmolytics, decubitus positioning and number of CT data acquisitions, faecal tagging, 2D vs. 3D reading, and reporting. CONCLUSION: The recommendations of the consensus should be useful for both the radiologist who is starting a CTC service and for those who have already implemented the technique but whose practice may need updating. KEY POINTS : • Computed tomographic colonography is the optimal radiological method of assessing the colon • This article reviews ESGAR quality standards for CT colonography • This article is aimed to provide CT-colonography guidelines for practising radiologists • The recommendations should help radiologists who are starting/updating their CTC services.
|
|
| 5. |
- Pircs, Karolina, et al.
(författare)
-
Distinct subcellular autophagy impairments in induced neurons from patients with Huntington's disease
- 2022
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:9, s. 3035-3057
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in aging humans. To address this, we generated induced neurons (iNs) through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. HD-iNs displayed profound deficits in autophagy, characterised by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in ctrl-iNs, highlighting the importance of wild type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington's disease neurons and provides a new rational for future development of autophagy activation therapies.
|
|
| 6. |
- Sardanelli, Francesco, et al.
(författare)
-
The Role of Imaging Specialists as Authors of Systematic Reviews on Diagnostic and Interventional Imaging and Its Impact on Scientific Quality : Report from the EuroAIM Evidence-based Radiology Working Group
- 2014
-
Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 272:2, s. 533-540
-
Forskningsöversikt (refereegranskat)abstract
- Purpose: To evaluate the inclusion of radiologists or nuclear medicine physicians (imaging specialists) as authors of systematic reviews (SRs) on imaging and imaging-guided diagnostic procedures and to determine the impact of imaging specialists' presence as authors on the overall quality of the reviews.Materials and Methods: A MEDLINE and EMBASE search was performed for SRs of diagnostic and interventional image-guided procedures that were published from January 2001 to December 2010. SRs about procedures primarily performed by nonimaging specialists were excluded. The inclusion of imaging specialists among the SR authors and the frequency of publication in imaging journals were evaluated. The quality of a subset of 200 SRs (100 most recent SRs with imaging specialists as authors and 100 most recent SRs without imaging specialists as authors) was rated by using a 12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman, chi(2), and Mann-Whitney statistics were used.Results: From among 3258 retrieved citations, 867 SRs were included in the study. Neuroimaging had the largest number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic performance, and 26% (228 of 867) of SRs were published in imaging journals. Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging specialists as authors were more often published in imaging journals than in nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median number of modified AMSTAR quality indicators was nine in SRs with imaging specialists as authors, while that in SRs without imaging specialists as authors was seven (P = .003).Conclusion: Only 38% (330 of 867) of SRs on radiology or nuclear medicine-related imaging published from January 2001 to December 2010 included imaging specialists as authors. However, the inclusion of imaging specialists as authors was associated with a significant increase in the scientific quality (as judged by using a modified AMSTAR scale) of the SR.
|
|
| 7. |
|
|
| 8. |
- Schiffer, Christian, et al.
(författare)
-
Structural inheritance in the North Atlantic
- 2020
-
Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 206
-
Forskningsöversikt (refereegranskat)abstract
- The North Atlantic, extending from the Charlie Gibbs Fracture Zone to the north Norway-Greenland-Svalbard margins, is regarded as both a classic case of structural inheritance and an exemplar for the Wilson-cycle concept. This paper examines different aspects of structural inheritance in the Circum-North Atlantic region: 1) as a function of rejuvenation from lithospheric to crustal scales, and 2) in terms of sequential rifting and opening of the ocean and its margins, including a series of failed rift systems. We summarise and evaluate the role of fundamental lithospheric structures such as mantle fabric and composition, lower crustal inhomogeneities, orogenic belts, and major strike-slip faults during breakup. We relate these to the development and shaping of the NE Atlantic rifted margins, localisation of magmatism, and microcontinent release. We show that, although inheritance is common on multiple scales, the Wilson Cycle is at best an imperfect model for the Circum-North Atlantic region. Observations from the NE Atlantic suggest depth dependency in inheritance (surface, crust, mantle) with selective rejuvenation depending on time-scales, stress field orientations and thermal regime. Specifically, post-Caledonian reactivation to form the North Atlantic rift systems essentially followed pre-existing orogenic crustal structures, while eventual breakup reflected a change in stress field and exploitation of a deeper-seated, lithospheric-scale shear fabrics. We infer that, although collapse of an orogenic belt and eventual transition to a new ocean does occur, it is by no means inevitable.
|
|
| 9. |
- Spada, Cristiano, et al.
(författare)
-
Clinical indications for computed tomographic colonography: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline.
- 2014
-
Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 46:10, s. 897-915
-
Tidskriftsartikel (refereegranskat)abstract
- This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of computed tomographic colonography (CTC). A targeted literature search was performed to evaluate the evidence supporting the use of CTC. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. ESGE/ESGAR do not recommend barium enema in this setting (strong recommendation, high quality evidence). 2 ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. Delay of CTC should be considered following endoscopic resection. In the case of obstructing colorectal cancer, preoperative contrast-enhanced CTC may also allow location or staging of malignant lesions (strong recommendation, moderate quality evidence). 3 When endoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with symptoms suggestive of colorectal cancer (strong recommendation, high quality evidence). 4 ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥ 6 mm in diameter detected at CTC. CTC surveillance may be clinically considered if patients do not undergo polypectomy (strong recommendation, moderate quality evidence). 5 ESGE/ESGAR do not recommend CTC as a primary test for population screening or in individuals with a positive first-degree family history of colorectal cancer (CRC). However, it may be proposed as a CRC screening test on an individual basis providing the screenee is adequately informed about test characteristics, benefits, and risks (weak recommendation, moderate quality evidence).
|
|
| 10. |
|
|
