| 1. |
- Keck, Michaela Kristina, et al.
(författare)
-
Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
-
Tidskriftsartikel (refereegranskat)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
|
|
| 2. |
- Sawcer, Stephen, et al.
(författare)
-
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
|
|
| 3. |
- Kalaria, Raj, et al.
(författare)
-
The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
- 2024
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
-
Tidskriftsartikel (refereegranskat)abstract
- Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
|
|
| 4. |
- Adare, A., et al.
(författare)
-
Inclusive cross section and double-helicity asymmetry for pi(0) production at midrapidity in p plus p collisions at root s=510 GeV
- 2016
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 93:1
-
Tidskriftsartikel (refereegranskat)abstract
- PHENIX measurements are presented for the cross section and double-helicity asymmetry (A(LL)) in inclusive pi(0) production at midrapidity from p + p collisions at root s = 510 GeV from data taken in 2012 and 2013 at the Relativistic Heavy Ion Collider. The next-to-leading-order perturbative-quantum-chromodynamics theory calculation is in excellent agreement with the presented cross section results. The calculation utilized parton-to-pion fragmentation functions from the recent DSS14 global analysis, which prefer a smaller gluon-to-pion fragmentation function. The pi(0)A(LL) results follow an increasingly positive asymmetry trend with p(T) and root s with respect to the predictions and are in excellent agreement with the latest global analysis results. This analysis incorporated earlier results on pi(0) and jet A(LL) and suggested a positive contribution of gluon polarization to the spin of the proton Delta G for the gluon momentum fraction range x > 0.05. The data presented here extend to a currently unexplored region, down to x similar to 0.01, and thus provide additional constraints on the value of Delta G.
|
|
| 5. |
- Adare, A., et al.
(författare)
-
Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review Letters. - 1079-7114. ; 115:14
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
|
|
| 6. |
- Adare, A., et al.
(författare)
-
phi meson production in d plus Au collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:4
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX Collaboration has measured phi meson production in d + Au collisions at root s(NN) = 200 GeV using the dimuon and dielectron decay channels. The phi meson is measured in the forward (backward) d-going (Au-going) direction, 1.2 < y < 2.2 (-2.2 < y < -1.2) in the transverse-momentum (pT) range from 1-7 GeV/c and at midrapidity vertical bar y vertical bar < 0.35 in the p(T) range below 7 GeV/c. The phi meson invariant yields and nuclear-modification factors as a function of p(T), rapidity, and centrality are reported. An enhancement of phi meson production is observed in the Au-going direction, while suppression is seen in the d-going direction, and no modification is observed at midrapidity relative to the yield in p + p collisions scaled by the number of binary collisions. Similar behavior was previously observed for inclusive charged hadrons and open heavy flavor, indicating similar cold-nuclear-matter effects.
|
|
| 7. |
- Adare, A., et al.
(författare)
-
Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
-
Tidskriftsartikel (refereegranskat)abstract
- The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
|
|
| 8. |
- Adare, A., et al.
(författare)
-
Systematic study of charged-pion and kaon femtoscopy in Au plus Au collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
-
Tidskriftsartikel (refereegranskat)abstract
- We present a systematic study of charged-pion and kaon interferometry in Au + Au collisions at root s(NN) = 200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.
|
|
| 9. |
- Adare, A., et al.
(författare)
-
Cross section and transverse single-spin asymmetry of eta mesons in p up arrow plus p collisions at root s=200 GeV at forward rapidity
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:7
-
Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the cross section and transverse single-spin asymmetry (AN) for. mesons at large pseudorapidity from root s = 200 GeV p up arrow + p collisions. The measured cross section for 0.5 < p(T) < 5.0 GeV/c and 3.0 < vertical bar eta vertical bar < 3.8 is well described by a next-to-leading-order perturbative-quantum-chromodynamics calculation. The asymmetries A(N) have been measured as a function of Feynman-x (x(F)) from 0.2 < vertical bar x(F)vertical bar < 0.7, as well as transverse momentum (p(T)) from 1.0 < p(T) < 4.5 GeV/c. The asymmetry averaged over positive x(F) is < A(N)> = 0.061 +/- 0.014. The results are consistent with prior transverse single-spin measurements of forward eta and pi(0) mesons at various energies in overlapping x(F) ranges. Comparison of different particle species can help to determine the origin of the large observed asymmetries in p up arrow + p collisions.
|
|
| 10. |
- Adare, A., et al.
(författare)
-
Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
|
|
| 11. |
- Adare, A., et al.
(författare)
-
Measurement of K-S(0) and K*(0) in p plus p, d plus Au, and Cu plus Cu collisions at root s(NN)=200 GeV
- 2014
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K-S(0) and K*(0) meson production at midrapidity in p + p, d + Au, and Cu + Cu collisions at root s(NN) = 200 GeV. The K-S(0) and K*(0) mesons are reconstructed via their K-S(0) -> pi(0)(-> gamma gamma) pi(0)(-> gamma gamma) and K*(0) -> K-+/-pi(-/+) decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K-S(0) and K*(0) mesons in d + Au and Cu + Cu collisions at different centralities. In the d + Au collisions, the nuclear modification factor of K-S(0) and K*(0) mesons is almost constant as a function of transverse momentum and is consistent with unity, showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu + Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p + p yield scaled by the number of binary nucleon-nucleon collisions in the Cu + Cu system. In the p(T) range 2-5 GeV/c, the strange mesons (K-S(0), K*(0)) similarly to the phi meson with hidden strangeness, showan intermediate suppression between the more suppressed light quark mesons (pi(0)) and the nonsuppressed baryons (p, (p) over bar). At higher transverse momentum, p(T) > 5 GeV/c, production of all particles is similarly suppressed by a factor of approximate to 2.
|
|
| 12. |
- Adare, A., et al.
(författare)
-
Nuclear matter effects on J/psi production in asymmetric Cu plus Au collisions at root S-NN=200 GeV
- 2014
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:6
-
Tidskriftsartikel (refereegranskat)abstract
- We report on J/psi production from asymmetric Cu + Au heavy-ion collisions at root S-NN = 200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of J/psi yields in Cu + Au collisions in the Au-going direction is found to be comparable to that inAu + Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, J/psi production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-x gluon suppression in the larger Au nucleus.
|
|
| 13. |
- Draper-Joyce, Christopher J., et al.
(författare)
-
Positive allosteric mechanisms of adenosine A(1) receptor-mediated analgesia
- 2021
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 597:7877, s. 571-576
-
Tidskriftsartikel (refereegranskat)abstract
- The adenosine A(1) receptor (A,R) is a promising therapeutic target for non-opioid analgesic agents to treat neuropathic pain(1,2). However, development of analgesic orthosteric A(1)R agonists has failed because of a lack of sufficient on-target selectivity as well as off-tissue adverse effects(3). Here we show that [2-amino-4-(3,5-bis(trifluoromethyl) phenyl)thiophen-3-yl)(4-chlorophenyl)methanone] (MIPS521), a positive allosteric modulator of the A(1)R, exhibits analgesic efficacy in rats in vivo through modulation of the increased levels of endogenous adenosine that occur in the spinal cord of rats with neuropathic pain. We also report the structure of the co-bound to adenosine, MIPS521 and a G(12) heterotrimer, revealing an extrahelicallipid-detergent-facing allosteric binding pocket that involves transmembrane helixes 1, 6 and 7. Molecular dynamics simulations and ligand kinetic binding experiments support a mechanism whereby MIPS521 stabilizes the adenosine-receptor-G protein complex. This study provides proof of concept for structure-based allosteric drug design of non-opioid analgesic agents that are specific to disease contexts.
|
|
| 14. |
- Durante-Mangoni, Emanuele, et al.
(författare)
-
Current features of infective endocarditis in elderly patients: Results of the international collaboration on endocarditis prospective cohort study
- 2008
-
Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 168, s. 2095-2103
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. Methods: In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. Results: Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. Conclusions: In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE. ©2008 American Medical Association. All rights reserved.
|
|
| 15. |
- Fjell, Anders M., et al.
(författare)
-
No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy
- 2023
-
Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:11, s. 2008-2022
-
Tidskriftsartikel (refereegranskat)abstract
- Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.
|
|
| 16. |
- Fjell, Anders M., et al.
(författare)
-
Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
- 2021
-
Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
-
Tidskriftsartikel (refereegranskat)abstract
- We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
|
|
| 17. |
- Fjell, Anders M., et al.
(författare)
-
Self-reported sleep relates to hippocampal atrophy across the adult lifespan : results from the Lifebrain consortium
- 2020
-
Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 43:5
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.Results: No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
|
|
| 18. |
|
|
| 19. |
- Friedman, Barbara Bodorkos, et al.
(författare)
-
Are People Ready for Personalized Brain Health? Perspectives of Research Participants in the Lifebrain Consortium
- 2020
-
Ingår i: The Gerontologist. - : Oxford University Press. - 0016-9013 .- 1758-5341. ; 60:6, s. E374-E383
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain.DESIGN AND METHODS: We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis.RESULTS: Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries.DISCUSSION AND IMPLICATIONS: Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.
|
|
| 20. |
- Grydeland, Håkon, et al.
(författare)
-
Self-reported sleep relates to microstructural hippocampal decline in beta-amyloid positive Adults beyond genetic risk
- 2021
-
Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 44:11
-
Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: A critical role linking sleep with memory decay and beta-amyloid (A beta) accumulation, two markers of Alzheimer's disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of A beta.Methods: Two-hundred and forty-three cognitively healthy participants, aged 19-81 years, completed the Pittsburgh Sleep Quality Index once, and two diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 A beta positive. Genotyping enabled control for APOE epsilon 4 status, and polygenic scores for sleep and AD, respectively.Results: Worse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of A beta accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD.Conclusions: Worse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of A beta accumulation, and A beta might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown.
|
|
| 21. |
|
|
| 22. |
- Lalani, Tahaniyat, et al.
(författare)
-
In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis
- 2013
-
Ingår i: JAMA Internal Medicine. - : American Medical Association (AMA). - 2168-6106. ; 173:16, s. 1495-1504
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.
|
|
| 23. |
|
|
| 24. |
- Winkelmann, Iven, et al.
(författare)
-
Structure and elevator mechanism of the mammalian sodium/proton exchanger NHE9
- 2020
-
Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:24
-
Tidskriftsartikel (refereegranskat)abstract
- Na+/H+ exchangers (NHEs) are ancient membrane-bound nanoma- chines that work to regulate intracellular pH, sodium levels and cell volume. NHE activities contribute to the control of the cell cycle, cell proliferation, cell migration and vesicle trafficking. NHE dysfunction has been linked to many diseases, and they are targets of pharma- ceutical drugs. Despite their fundamental importance to cell home- ostasis and human physiology, structural information for the mammalian NHEs was lacking. Here, we report the cryogenic elec- tron microscopy structure of NHE isoform 9 (SLC9A9) from Equus caballus at 3.2 Å resolution, an endosomal isoform highly expressed in the brain and associated with autism spectrum (ASD) and atten- tion deficit hyperactivity (ADHD) disorders. Despite low sequence identity, the NHE9 architecture and ion-binding site are remarkably most similar to distantly related bacterial Na+/H+ antiporters with 13 transmembrane segments. Collectively, we reveal the conserved architecture of the NHE ion-binding site, their elevator-like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications.
|
|
| 25. |
- Zhang, Yurui, et al.
(författare)
-
Early Eocene Ocean Meridional Overturning Circulation : The Roles of Atmospheric Forcing and Strait Geometry
- 2022
-
Ingår i: Paleoceanography and Paleoclimatology. - 2572-4517 .- 2572-4525. ; 37:3
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we compare the ocean overturning circulation of the early Eocene (47–56 Ma) in eight coupled climate model simulations from the Deep-Time Model Intercomparison Project (DeepMIP) and investigate the causes of the observed inter-model spread. The most common global meridional overturning circulation (MOC) feature of these simulations is the anticlockwise bottom cell, fed by sinking in the Southern Ocean. In the North Pacific, one model (GFDL) displays strong deepwater formation and one model (CESM) shows weak deepwater formation, while in the Atlantic two models show signs of weak intermediate water formation (MIROC and NorESM). The location of the Southern Ocean deepwater formation sites varies among models and relates to small differences in model geometry of the Southern Ocean gateways. Globally, convection occurs in the basins with smallest local freshwater gain from the atmosphere. The global MOC is insensitive to atmospheric CO2 concentrations from 1× (i.e., 280 ppm) to 3× (840 ppm) pre-industrial levels. Only two models have simulations with higher CO2 (i.e., CESM and GFDL) and these show divergent responses, with a collapsed and active MOC, respectively, possibly due to differences in spin-up conditions. Combining the multiple model results with available proxy data on abyssal ocean circulation highlights that strong Southern Hemisphere-driven overturning is the most likely feature of the early Eocene. In the North Atlantic, unlike the present day, neither model results nor proxy data suggest deepwater formation in the open ocean during the early Eocene, while the evidence for deepwater formation in the North Pacific remains inconclusive.
|
|
