| 1. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Khatri, C, et al.
(author)
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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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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)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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| 6. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 12. |
- Lundgren, Jens D, et al.
(author)
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Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.
- 2023
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In: NEJM evidence. - : Massachusetts Medical Society. - 2766-5526. ; 2:3
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Journal article (peer-reviewed)abstract
- For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 13. |
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| 14. |
- Carville, N. C., et al.
(author)
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Growth mechanism of photoreduced silver nanostructures on periodically proton exchanged lithium niobate : Time and concentration dependence
- 2013
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 113:18, s. 187212-1-187212-7
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Journal article (peer-reviewed)abstract
- Photodeposition of metallic nanostructures onto ferroelectric surfaces, which have been chemically patterned using a proton exchange process, has recently been demonstrated. By varying the molar concentration of the AgNO 3 solution and the illumination time, one can determine the initial nucleation sites, control the rate of nucleation and the height of silver nanostructures formed, and study the mechanisms by which these processes occurs. The nanoparticles are found to deposit preferentially in the boundary between ferroelectric and proton exchanged regions, in an area proton exchanged via lateral diffusion under the masking layer used for chemical patterning, consistent with our previous results. Using a short illumination time (3 min), we are able to determine that the initial nucleation of the silver nanostructure, having a width of 0.17 ± 0.02 μm and a height of 1.61 ± 0.98 nm, occurs near the edge of the reactive ion etched area within this lateral diffusion region. Over longer illumination times (15 min), we find that the silver deposition has spread to a width of 1.29 ± 0.06 μm, extending across the entire lateral diffusion region. We report that at a high molar concentration of AgNO3 (10-2 M), the amount of silver deposition for 5 min UV illumination is greater (2.88 ± 0.58 nm) compared to that at low (10-4 M) concentrations (0.78 ± 0.35 nm), however, this is not the case for longer time periods. With increasing illumination time (15 min), experiments at 10-4 M had greater overall deposition, 6.90 ± 1.52 nm, compared to 4.50 ± 0.76 nm at 10 -2 M. For longer exposure times (30 min) at 10-2 M, the nanostructure height is 4.72 ± 0.59 nm, suggesting a saturation in the nanostructure height. The results are discussed in terms of the electric double layer that forms at the crystal surface. There is an order of magnitude difference between the Debye lengths for 10-2 and 10-4 M solutions, i.e., 3.04 vs. 30.40 nm, which suggests the Debye length plays a role in the availability of Ag ions at the surface.
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| 15. |
- Carville, N. Craig, et al.
(author)
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Photoreduction of SERS-Active Metallic Nanostructures on Chemically Patterned Ferroelectric Crystals
- 2012
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 6:8, s. 7373-7380
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Journal article (peer-reviewed)abstract
- Photodeposition of metallic nanostructures onto ferroelectric surfaces is typically based on patterning local surface reactivity via electric field poling. Here, we demonstrate metal deposition onto substrates which have been chemically patterned via proton exchange (i.e., without polarization reversal). The chemical patterning provides the ability to tailor the electrostatic fields near the surface of lithium niobate crystals, and these engineered fields are used to fabricate metallic nanostructures. The effect of the proton exchange process on the piezoelectric and electrostatic properties of the surface is characterized using voltage-modulated atomic force microscopy techniques, which, combined with modeling of the electric fields at the surface of the crystal, reveal that the deposition occurs preferentially along the boundary between ferroelectric and proton-exchanged regions. The metallic nanostructures have been further functionalized with a target probe molecule, 4-aminothiophenol, from which surface-enhanced Raman scattering (SERS) signal is detected, demonstrating the suitability of chemically patterned ferroelectrics as SERS-active templates.
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| 16. |
- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 17. |
- Galea Holmes, Melissa N., et al.
(author)
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Physiotherapy informed by Acceptance and Commitment Therapy for chronic low back pain : A mixed-methods treatment fidelity evaluation
- 2022
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In: British Journal of Health Psychology. - : John Wiley & Sons. - 1359-107X .- 2044-8287. ; 27:3, s. 935-955
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Journal article (peer-reviewed)abstract
- Objectives A randomized controlled trial of a new type of Physiotherapy informed by Acceptance and Commitment Therapy (PACT), found that it improved functioning in people with chronic low back pain compared to usual physiotherapy care. Fidelity evaluation is necessary to understand trial processes and outcomes. This study evaluated PACT treatment fidelity including delivery, receipt, and enactment. Design A mixed-methods study nested within a randomized controlled trial was conducted. Methods A total of 72 (20% of total) PACT treatment audio files were independently assessed by two raters, according to a novel framework developed to measure PACT treatment content adherence, therapeutic alliance, ACT competence, and treatment enactment. Interview transcripts from 19 trial participants randomized to PACT were analysed thematically for evidence of treatment receipt and enactment. Results PACT physiotherapists delivered treatment as intended with high content adherence and satisfactory therapeutic alliance, but ACT competence was low. Qualitative findings indicated participant receipt of 11/17 and enactment of 3/17 components; 89% (n = 17) and 47% (n = 9) of participants reported treatment receipt and enactment of at least one component, respectively. Conclusions This mixed-methods study of PACT treatment demonstrated high fidelity reflecting treatment content delivery and receipt, and therapeutic alliance. There was some evidence of treatment enactment in participants with chronic low back pain. Low ACT competence could be addressed through additional support and adaptations to therapeutic processes for delivery by physiotherapists.
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| 18. |
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| 19. |
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| 20. |
- Johnson, Benjamin B., et al.
(author)
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Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes
- 2024
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In: Cell Reports. - : Elsevier. - 2211-1247. ; 43:1
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Journal article (peer-reviewed)abstract
- Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2(+/-)) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late -stage HSPG2(+/-) hPSC-CMs have immature features, including reduced alpha-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecanpeptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure.
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| 21. |
- Nava, Porfirio, et al.
(author)
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IFN gamma-induced suppression of beta-catenin signaling : evidence for roles of Akt and 14.3.3 zeta
- 2014
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In: Molecular Biology of the Cell. - Bethesda, United States : American Society for Cell Biology. - 1059-1524 .- 1939-4586. ; 25:19, s. 2894-2904
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Journal article (peer-reviewed)abstract
- The proinflammatory cytokine interferon gamma (IFNgamma ) influences intestinal epithelial cell (IEC) homeostasis in a biphasic manner by acutely stimulating proliferation that is followed by sustained inhibition of proliferation despite continued mucosal injury. beta-Catenin activation has been classically associated with increased IEC proliferation. However, we observed that IFNgamma inhibits IEC proliferation despite sustained activation of Akt/beta-catenin signaling. Here we show that inhibition of Akt/beta-catenin-mediated cell proliferation by IFNgamma is associated with the formation of a protein complex containing phosphorylated beta-catenin 552 (pbeta-cat552) and 14.3.3zeta. Akt1 served as a bimodal switch that promotes or inhibits beta-catenin transactivation in response to IFNgamma stimulation. IFNgamma initially promotes beta-catenin transactivation through Akt-dependent C-terminal phosphorylation of beta-catenin to promote its association with 14.3.3zeta. Augmented beta-catenin transactivation leads to increased Akt1 protein levels, and active Akt1 accumulates in the nucleus, where it phosphorylates 14.3.3zeta to translocate 14.3.3zeta/beta-catenin from the nucleus, thereby inhibiting beta-catenin transactivation and IEC proliferation. These results outline a dual function of Akt1 that suppresses IEC proliferation during intestinal inflammation.
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| 22. |
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| 23. |
- Wuestefeld, Anika, et al.
(author)
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Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
- 2023
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Other publication (other academic/artistic)abstract
- The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 µm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.
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| 24. |
- Wuestefeld, Anika, et al.
(author)
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Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
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In: Hippocampus. - 1050-9631.
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Journal article (peer-reviewed)abstract
- The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.
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