| 1. |
- Folkersen, Lasse, et al.
(författare)
-
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
|
|
| 2. |
- Lymeus, Freddie, et al.
(författare)
-
Mindfulness-Based Restoration Skills Training (ReST) in a Natural Setting Compared to Conventional Mindfulness Training : Psychological Functioning After a Five-Week Course
- 2020
-
Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Restoration skills training (ReST) is a mindfulness-based course that draws on restorative nature experience to facilitate the meditation practice and teach widely applicable adaptation skills. Previous studies comparing ReST to conventional mindfulness training (CMT) showed that ReST has important advantages: it supports beginning meditators in connecting with restorative environmental qualities and in meditating with less effort; it restores their attention regulation capabilities; and it helps them complete the course and establish a regular meditation habit. However, mindfulness theory indicates that effortful training may be necessary to achieve generalized improvements in psychological functioning. Therefore, this study tests whether the less effortful and more acceptable ReST approach is attended by any meaningful disadvantage compared to CMT in terms of its effects on central aspects psychological functioning. We analyze data from four rounds of development of the ReST course, in each of which we compared it to a parallel and formally matched CMT course. Randomly assigned participants (total course starters = 152) provided ratings of dispositional mindfulness, cognitive functioning, and chronic stress before and after the 5-week ReST and CMT courses. Round 4 also included a separately recruited passive control condition. ReST and CMT were attended by similar average improvements in the three outcomes, although the effects on chronic stress were inconsistent. Moderate to large improvements in the three outcomes could also be affirmed in contrasts with the passive controls. Using a reliable change index, we saw that over one third of the ReST and CMT participants enjoyed reliably improved psychological functioning. The risk of experiencing deteriorated functioning was no greater with either ReST or CMT than for passive control group participants. None of the contrasts exceeded our stringent criterion for inferiority of ReST compared with CMT. We conclude that ReST is a promising alternative for otherwise healthy people with stress or concentration problems who would be less likely to complete more effortful CMT. By adapting the meditation practices to draw on restorative setting characteristics, ReST can mitigate the demands otherwise incurred in early stages of mindfulness training without compromising the acquisition of widely applicable mindfulness skills.
|
|
| 3. |
- Abdellah, Tebani, et al.
(författare)
-
Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
|
|
| 4. |
- Cassinger, Cecilia, et al.
(författare)
-
Vad är överturism? : En kunskapsöversikt
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Turism dominerar alltmer det sociala livet i städerna. Detökade flödet av turister till vissa storstäder i Europa lämnarefter sig problem kopplat till trängsel, nedskräpning, trafik,prissättning på bostäder och missnöjesyttringar bland lokalastadsbor.Överturism beskriver ett tillstånd när det kommer så mångaturister till en plats att det får negativ påverkan på såvällokalbefolkningens livskvalitet som på turisternas upplevelse avplatsen. Denna rapport ger en översikt av den internationellaforskningen kring överturism som ett socialt fenomen. Genomatt beskriva överturismens olika definitioner, drivkrafteroch platseffekter är syftet med rapporten att öka förståelsenför dess utbredning och konsekvenser för besöksnäringen.Resonemanget blickar också framåt och ger förslag på åtgärderoch alternativa sätt att tänka, vilket främjar en framtida hållbarturismutveckling. Rapporten riktar sig främst till aktörer inomsvensk besöksnäring, exempelvis i kommuner, regioner ochföretag.
|
|
| 5. |
- Chrapkowska, Cecilia, et al.
(författare)
-
Validation of the new Swedish vaccination register – Accuracy and completeness of register data
- 2020
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 38:25, s. 4104-4110
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aims of this study are to validate infant vaccination data in the Swedish Vaccination Register (SVR) to the Swedish administrative coverage reports, and to assess differences in register-based vaccination coverage estimates between providers using different data reporting methods. Methods: The study population included all infants born in Sweden with a Swedish Personal Identity Number during 2014 and 2015 (n = 230,220). Data on all National Immunisation Programme vaccinations administered before 24 months of age were collected from the SVR and from administrative coverage reports. Information regarding data registration methods in the SVR were collected from national and regional authorities. Coverage from health care providers using single registration methods, where vaccination data were transferred automatically from the electronic health care record to the SVR, was compared to that from providers using double registration methods where data had to be added into the SVR in a separate process. Results: For 98,4% of the study population at least one vaccination was recorded in the SVR. The coverage of 3-dose DTP-containing (87,1%) and 1 dose MMR (91,1%) in the register did not reach administrative data coverage (97,4% for 3-dose DTP-containing and 97,0% for MMR). Single registration procedures yielded significantly higher coverage than double registration procedures (92,24% vs 87,10%, p < 0,0001). A regional switch from double to single registration increased coverage from 80,0 to 95,2%. Conclusions: The SVR is a valuable data source for vaccination coverage monitoring. For research purposes, the SVR provides valuable data, since every health care provider is obliged to register all vaccine doses given within the national immunisation program. The SVR shows a high completeness validated by comparison to a very well-functioning administrative data system. Single-registration procedures give more complete data and should be supported by health systems while creating health care registers.
|
|
| 6. |
|
|
| 7. |
- Franzén, Cecilia, et al.
(författare)
-
Trust as an analytical concept for the study of welfare programmes to reduce child health disparities : the case of a Swedish postnatal home visiting programme
- 2020
-
Ingår i: Children and youth services review. - : Elsevier. - 0190-7409 .- 1873-7765. ; 118, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this article is to outline a theoretical framework for how the concept of trust can be used as analytical tool for a study of the aim, design, output and societal legitimacy of a Swedish welfare programme conducted to reduce disparities in health and social inequities and to give newborn a positive start in life. This programme, labelled Grow Safely, implies that home visits will be conducted at six occasions at first-time parents by different professionals: child health care nurses, midwifes, dental hygienists and counsellors from the social services. Prior to when the intervention is carried out, the involved professionals in the programme will be participating in training in order to increase the possibility that the home visits will be carried out in similar ways and be followed the same manual throughout the programme.The welfare programme will be based on relationships on different levels: between professionals and parents, between different professionals, between professionals and managers, and between organisations. Trust is believed to be of significance for the development of relationships as well as for the social legitimacy of the implantation of welfare programmes. Therefore, our ambition is to embrace a broad perspective on trust, combining insights from a variety of research traditions and analyses on macro, meso and micro levels in the outline a model for how the concept of trust can be used as an analytical tool for studying welfare programmes like Grow Safely. We argue for that the model can capture the significance of trust at different levels: individual, professional, organisational and societal levels as well as interplays between these levels, and consequently be useful in to analyse implementations of welfare programmes.
|
|
| 8. |
- Hage, Camilla, et al.
(författare)
-
Metabolomic Profile in HFpEF vs HFrEF Patients
- 2020
-
Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 26:12, s. 1050-1059
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are associated with metabolic derangements, which may have different pathophysiological implications.Methods and Results: In new-onset HFpEF (EF of >= 50%, n = 46) and HFrEF (EF of <40%, n = 75) patients, 109 endogenous plasma metabolites including amino acids, phospholipids and acylcarnitines were assessed using targeted metabolomics. Differentially altered metabolites and associations with clinical characteristics were explored. Patients with HFpEF were older, more often female with hypertension, atrial fibrillation, and diabetes compared with patients with HFrEF. Patients with HFpEF displayed higher levels of hydroxyproline and symmetric dimethyl arginine, alanine, cystine, and kynurenine reflecting fibrosis, inflammation and oxidative stress. Serine, cGMP, cAMP, L-carnitine, lysophophatidylcholine (18:2), lactate, and arginine were lower compared with patients with HFrEF. In patients with HFpEF with diabetes, kynurenine was higher (P = .014) and arginine lower (P = .014) vs patients with no diabetes, but did not differ with diabetes status in HFrEF. Decreasing kynurenine was associated with higher eGFR only in HFpEF (P-interaction = .020).Conclusions: Patients with new-onset HFpEF compared with patients with new-onset HFrEF display a different metabolic profile associated with comorbidities, such as diabetes and kidney dysfunction. HFpEF is associated with indices of increased inflammation and oxidative stress, impaired lipid metabolism, increased collagen synthesis, and downregulated nitric oxide signaling. Together, these findings suggest a more predominant systemic microvascular endothelial dysfunction and inflammation linked to increased fibrosis in HFpEF compared with HFrEF.
|
|
| 9. |
- Holmkvist, Alexander Dontsios, et al.
(författare)
-
Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice
- 2020
-
Ingår i: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neural interfaces often elicit inflammatory responses and neuronal loss in the surrounding tissue which adversely affect the function and longevity of the implanted device. Minocycline, an anti-inflammatory pharmaceutics with neuroprotective properties, may be used for reducing the acute brain tissue responses after implantation. However, conventional administration routes require high doses which can cause adverse systemic side effects. Therefore, the aim of this study was to develop and evaluate a new drug-delivery-system for local and sustained administration of minocycline in the brain. Methods: Stainless steel needles insulated with Parylene-C were dip-coated with non-crosslinked gelatin and minocycline-loaded PLGA nanoparticles (MC-NPs) were incorporated into the gelatin-coatings by an absorption method and subsequently trapped by drying the gelatin. Parylene-C insulated needles coated only with gelatin were used as controls. The expression of markers for activated microglia (CD68), all microglia (CX3CR1-GFP), reactive astrocytes (GFAP), neurons (NeuN) and all cell nuclei (DAPI) surrounding the implantation sites were quantified at 3 and 7 days after implantation in mice. Results: MC-NPs were successfully incorporated into gelatin-coatings of neural implants by an absorption method suitable for thermosensitive drug-loads. Immunohistochemical analysis of the in vivo brain tissue responses, showed that MC-NPs significantly attenuate the activation of microglial cells without effecting the overall population of microglial cells around the implantation sites. A delayed but significant reduction of the astrocytic response was also found in comparison to control implants. No effect on neurons or total cell count was found which may suggest that the MC-NPs are non-toxic to the central nervous system. Conclusions: A novel drug-nanoparticle-delivery-system was developed for neural interfaces and thermosensitive drug-loads. The local delivery of MC-NPs was shown to attenuate the acute brain tissue responses nearby an implant and therefore may be useful for improving biocompatibility of implanted neuro-electronic interfaces. The developed drug-delivery-system may potentially also be used for other pharmaceutics to provide highly localized and therefore more specific effects as compared to systemic administration.
|
|
| 10. |
- Hong, Mun-Gwan, et al.
(författare)
-
Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
- 2020
-
Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:10, s. e202000817-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.
|
|
