| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 4. |
- Hochberg, Georg K A, et al.
(författare)
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Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 359:6378, s. 930-935
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Tidskriftsartikel (refereegranskat)abstract
- Oligomeric proteins assemble with exceptional selectivity, even in the presence of closely related proteins, to perform their cellular roles. We show that most proteins related by gene duplication of an oligomeric ancestor have evolved to avoid hetero-oligomerization and that this correlates with their acquisition of distinct functions. We report how coassembly is avoided by two oligomeric small heat-shock protein paralogs. A hierarchy of assembly, involving intermediates that are populated only fleetingly at equilibrium, ensures selective oligomerization. Conformational flexibility at noninterfacial regions in the monomers prevents coassembly, allowing interfaces to remain largely conserved. Homomeric oligomers must overcome the entropic benefit of coassembly and, accordingly, homomeric paralogs comprise fewer subunits than homomers that have no paralogs.
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| 5. |
- Kemaladewi, Dwi U, et al.
(författare)
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A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7767, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. MDC1A is caused by mutations in LAMA2 that lead to nonfunctional laminin-α2, which compromises the stability of muscle fibres and the myelination of peripheral nerves. Transgenic overexpression of Lama1, which encodes a structurally similar protein called laminin-α1, ameliorates muscle wasting and paralysis in mouse models of MDC1A, demonstrating its importance as a compensatory modifier of the disease1. However, postnatal upregulation of Lama1 is hampered by its large size, which exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. We modulate expression of Lama1 in the dy2j/dy2j mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter. When pre-symptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. However, for many disorders it is important to investigate the therapeutic window and reversibility of symptoms. In muscular dystrophies, it has been hypothesized that fibrotic changes in skeletal muscle are irreversible. However, we show that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy2j/dy2j mice with apparent hindlimb paralysis and muscle fibrosis. Collectively, our data demonstrate the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.
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| 6. |
- Saba, L, et al.
(författare)
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Multinational Survey of Current Practice from Imaging to Treatment of Atherosclerotic Carotid Stenosis
- 2021
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 50:1, s. 108-120
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> In the last 20–30 years, there have been many advances in imaging and therapeutic strategies for symptomatic and asymptomatic individuals with carotid artery stenosis. Our aim was to examine contemporary multinational practice standards. <b><i>Methods:</i></b> Departmental Review Board approval for this study was obtained, and 3 authors prepared the 44 multiple choice survey questions. Endorsement was obtained by the European Society of Neuroradiology, American Society of Functional Neuroradiology, and African Academy of Neurology. A link to the online questionnaire was sent to their respective members and members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS). The questionnaire was open from May 16 to July 16, 2019. <b><i>Results:</i></b> The responses from 223 respondents from 46 countries were included in the analyses including 65.9% from academic university hospitals. Neuroradiologists/radiologists comprised 68.2% of respondents, followed by neurologists (15%) and vascular surgeons (12.9%). In symptomatic patients, half (50.4%) the respondents answered that the first exam they used to evaluate carotid bifurcation was ultrasound, followed by computed tomography angiography (CTA, 41.6%) and then magnetic resonance imaging (MRI 8%). In asymptomatic patients, the first exam used to evaluate carotid bifurcation was ultrasound in 88.8% of respondents, CTA in 7%, and MRA in 4.2%. The percent stenosis upon which carotid endarterectomy or stenting was recommended was reduced in the presence of imaging evidence of “vulnerable plaque features” by 66.7% respondents for symptomatic patients and 34.2% for asymptomatic patients with a smaller subset of respondents even offering procedural intervention to patients with <50% symptomatic or asymptomatic stenosis. <b><i>Conclusions:</i></b> We found heterogeneity in current practices of carotid stenosis imaging and management in this worldwide survey with many respondents including vulnerable plaque imaging into their decision analysis despite the lack of proven benefit from clinical trials. This study highlights the need for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention.
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| 7. |
- Saba, Luca, et al.
(författare)
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Carotid plaque-RADS : a novel stroke risk classification system
- 2024
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Ingår i: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591. ; 17:1, s. 62-75
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features.Objectives: The aim of this document is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque–Reporting and Data System (RADS) score.Methods: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports.Results: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of “stenosis.” The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories.Conclusions: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.
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| 8. |
- Singh, Digvijay, et al.
(författare)
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Evolution of gradient structured layer on AZ91D magnesium alloy and its corrosion behaviour
- 2021
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388. ; 882
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Tidskriftsartikel (refereegranskat)abstract
- This article investigates the microstructure evolution and corrosion response of surface mechanical attrition treated (SMAT) AZ91D magnesium alloy. In-depth transmission electron microscopy and combined isothermal calorimetry and pressure measurement technique, a novel and powerful tool for in situ monitoring of the magnesium corrosion process, are explored in the present study. A gradient structured layer of ~ 500 µm thickness with improved (~2.5 times) surface hardness is successfully obtained on the AZ91D alloy surface. SMAT introduces compressive residual stress in the treated layer. TEM results confirmed nanoscale grains of ~125 nm in topmost region and multiple deformation twin-modes, including 101¯2 〈101¯1〉 dense twins and 101¯1 – 101¯2 double twinning in SMATed layer. Twining of secondary twins is established in the TEM analysis. Moreover, a twin density gradient is evident within the treated layer, where it decreases with an increase in depth. After 24 h of immersion in 0.9% NaCl solution, the average corrosion rate of SMATed and non-SMATed specimens is ~11.0 and ~3.8 mm/year, respectively. The corrosion product on non-SMATed specimens has densely packed nano-flakes morphology; however, the SMATed surface shows two different morphologies: sparse nanowires and porous honeycomb-like structure. The SMATed specimen's lower corrosion resistance is attributed to the combined effect of the high density of defects, rougher surface, and smaller volume fraction of β phase at the surface.
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