| 1. |
- Signori, A, et al.
(författare)
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Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network
- 2023
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 94:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.MethodsAll patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3–4.ResultsA total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.ConclusionsContrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.
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| 2. |
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| 3. |
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| 4. |
- Bärebring, Linnea, et al.
(författare)
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Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
- 2020
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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| 5. |
- Chalise, P., et al.
(författare)
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Addressing Domestic Violence in Antenatal Care Environments in Nepal (ADVANCE) - study protocol for a randomized controlled trial evaluating a video intervention on domestic violence among pregnant women
- 2023
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDomestic violence (DV) prior to, and during pregnancy is associated with increased risks for morbidity and mortality. As pregnant women routinely attend antenatal care this environment can be used to offer support to women experiencing DV. We have developed a video intervention that focuses on the use of behavioral coping strategies, particularly regarding disclosure of DV experiences. The effectiveness of this intervention will be evaluated through a randomized controlled trial (RCT) and a concurrent process evaluation.MethodsAll pregnant women between 12-22 weeks of gestation attending routine antenatal care at two tertiary level hospitals in Nepal are invited to participate. DV is measured using the Nepalese version of the Abuse Assessment Screen (N-AAS). Additionally, we measure participants' mental health, use of coping strategies, physical activity, and food security through a Color-coded Audio Computer Assisted Self Interview (C-ACASI). Irrespective of DV status, women are randomized into the intervention or control arm using a computer-generated randomization program. The intervention arm views a short video providing information on DV, safety improving actions women can take with an emphasis on disclosing the violence to a trusted person along with utilizing helplines available in Nepal. The control group watches a video on maintaining a healthy pregnancy and when to seek healthcare. The primary outcome is the proportion of women disclosing their DV status to someone. Secondary outcomes are symptoms of anxiety and depression, coping strategies, the use of safety measures and attitudes towards acceptance of abuse. Follow-up is conducted after 32 weeks of gestation, where both the intervention and control group participants view the intervention video after completing the follow-up questionnaire. Additionally, a mixed methods process evaluation of the intervention will be carried out to explore factors influencing the acceptability of the intervention and the disclosure of DV, including a review of project documents, individual interviews, and focus group discussions with members of the research team, healthcare providers, and participants.DiscussionThis study will provide evidence on whether pregnant women attending regular antenatal visits can enhance their safety by disclosing their experiences of violence to a trusted person after receiving a video intervention.Trial registrationThe study is registered in ClinicalTrial.gov with identifier NCT05199935.
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| 6. |
- Henriksen, N. A., et al.
(författare)
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EHS and AHS guidelines for treatment of primary ventral hernias in rare locations or special circumstances
- 2020
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 4:2, s. 342-353
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Rare locations of hernias, as well as primary ventral hernias under certain circumstances (cirrhosis, dialysis, rectus diastasis, subsequent pregnancy), might be technically challenging. The aim was to identify situations where the treatment strategy might deviate from routine management. METHODS: The guideline group consisted of surgeons from the European and Americas Hernia Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in formulating the recommendations. The Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists were used to evaluate the quality of full-text papers. A systematic literature search was performed on 1 May 2018 and updated 1 February 2019. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was followed. RESULTS: Literature was limited in quantity and quality. A majority of the recommendations were graded as weak, based on low quality of evidence. In patients with cirrhosis or on dialysis, a preperitoneal mesh repair is suggested. Subsequent pregnancy is a risk factor for recurrence. Repair should be postponed until after the last pregnancy. For patients with a concomitant rectus diastasis or those with a Spigelian or lumbar hernia, no recommendation could be made for treatment strategy owing to lack of evidence. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias in patients with special conditions, including Spigelian and lumbar hernias. All recommendations were weak owing to a lack of evidence. Further studies are needed on patients with rectus diastasis, Spigelian and lumbar hernias.
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| 7. |
- Henriksen, N. A., et al.
(författare)
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Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and Americas Hernia Society
- 2020
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 107:3, s. 171-190
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Forskningsöversikt (refereegranskat)abstract
- Background: Umbilical and epigastric hernia repairs are frequently performed surgical procedures with an expected low complication rate. Nevertheless, the optimal method of repair with best short- and long-term outcomes remains debatable. The aim was to develop guidelines for the treatment of umbilical and epigastric hernias. Methods: The guideline group consisted of surgeons from Europe and North America including members from the European Hernia Society and the Americas Hernia Society. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done on 1 May 2018, and updated on 1 February 2019. Results: Literature reporting specifically on umbilical and epigastric hernias was limited in quantity and quality, resulting in a majority of the recommendations being graded as weak, based on low-quality evidence. The main recommendation was to use mesh for repair of umbilical and epigastric hernias to reduce the recurrence rate. Most umbilical and epigastric hernias may be repaired by an open approach with a preperitoneal flat mesh. A laparoscopic approach may be considered if the hernia defect is large, or if the patient has an increased risk of wound morbidity. Conclusion: This is the first European and American guideline on the treatment of umbilical and epigastric hernias. It is recommended that symptomatic umbilical and epigastric hernias are repaired by an open approach with a preperitoneal flat mesh.
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| 8. |
- Höglund, Andrey, 1985-, et al.
(författare)
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The methylation landscape and its role in domestication and gene regulation in the chicken
- 2020
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 4, s. 1713-1724
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Tidskriftsartikel (refereegranskat)abstract
- Domestication is one of the strongest examples of artificial selection and has produced some of the most extreme within-species phenotypic variation known. In the case of the chicken, it has been hypothesized that DNA methylation may play a mechanistic role in the domestication response. By inter-crossing wild-derived red junglefowl with domestic chickens, we mapped quantitative trait loci for hypothalamic methylation (methQTL), gene expression (eQTL) and behaviour. We find large, stable methylation differences, with 6,179 cis and 2,973 trans methQTL identified. Over 46% of the trans effects were genotypically controlled by five loci, mainly associated with increased methylation in the junglefowl genotype. In a third of eQTL, we find that there is a correlation between gene expression and methylation, while statistical causality analysis reveals multiple instances where methylation is driving gene expression, as well as the reverse. We also show that methylation is correlated with some aspects of behavioural variation in the inter-cross. In conclusion, our data suggest a role for methylation in the regulation of gene expression underlying the domesticated phenotype of the chicken.
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| 9. |
- Höglund, Andrey, et al.
(författare)
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The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
- 2024
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always
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| 10. |
- Höglund, Andrey, 1985-, et al.
(författare)
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The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
- 2024
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always display such an interaction. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. We utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals, to investigate the role that methylation plays in regulating gene expression on the Z chromosome. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. In addition, these MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes.
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| 11. |
- Iaffaldano, P, et al.
(författare)
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Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network
- 2021
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 27:10, s. 1543-1555
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Tidskriftsartikel (refereegranskat)abstract
- The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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| 12. |
- Jorgensen, A. A., et al.
(författare)
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Petabit-per-second data transmission using a chip-scale microcomb ring resonator source
- 2022
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 16:11, s. 798-802
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Tidskriftsartikel (refereegranskat)abstract
- Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers.
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| 13. |
- Kong, D., et al.
(författare)
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Single Dark-Pulse Kerr Comb Supporting 1.84 Pbit/s Transmission over 37-Core Fiber
- 2020
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Ingår i: Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS. - 1092-8081. ; 2020-May
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Konferensbidrag (refereegranskat)abstract
- We show that a single dark-pulse Kerr comb can generate high enough OSNR to carry 1.84 Pbit/s data, achieved by 223 WDM spectral lines modulated with 32-Gbaud, SNR-adapted probabilistically shaped DP-QAM, over a 37-core fiber.
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| 14. |
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| 15. |
- Mirian, C, et al.
(författare)
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Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis
- 2020
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 91:4, s. 378-387
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Tidskriftsartikel (refereegranskat)abstract
- TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought.MethodsWe applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs.ResultsTERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients.ConclusionsTERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification.Trial registration numberPROSPERO: CRD42018110566.
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| 16. |
- Penner, Andrew M., et al.
(författare)
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Within-job gender pay inequality in 15 countries
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:2, s. 184-189
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Tidskriftsartikel (refereegranskat)abstract
- Extant research on the gender pay gap suggests that men and women who do the same work for the same employer receive similar pay, so that processes sorting people into jobs are thought to account for the vast majority of the pay gap. Data that can identify women and men who do the same work for the same employer are rare, and research informing this crucial aspect of gender differences in pay is several decades old and from a limited number of countries. Here, using recent linked employer–employee data from 15 countries, we show that the processes sorting people into different jobs account for substantially less of the gender pay differences than was previously believed and that within-job pay differences remain consequential.
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| 17. |
- Antonini, Angelo, et al.
(författare)
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Validation and clinical value of the MANAGE-PD tool : A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications
- 2021
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 92, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. Methods: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts’ clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). Results: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). Conclusions: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.
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| 18. |
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| 19. |
- Davegårdh, Cajsa, et al.
(författare)
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VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.
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| 20. |
- Fogelholm, Jesper, 1986-, et al.
(författare)
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CREBBP and WDR 24 Identified as Candidate Genes for Quantitative Variation in Red-Brown Plumage Colouration in the Chicken
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Plumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signalling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilising a domestic × wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red-brown colouration in chickens. By treating colour as a quantitative rather than qualitative trait, we have identified both QTL and genes of small effect. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.
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| 21. |
- Henriksen, M. W., et al.
(författare)
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Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome
- 2020
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Ingår i: Brain & Development. - : Elsevier BV. - 0387-7604. ; 42:7, s. 484-495
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations. Methods: All available females diagnosed with RTT in Norway were invited to the study. Parents were interviewed, the girl or woman with RTT examined and medical records reviewed. All diagnoses were revisited according to the current diagnostic criteria and exome-based sequencing analyses were performed in individuals without an identified causative mutation. Participants were categorized according to genotypes and RTT diagnosis. Individuals with RTT with and without mutations in MECP2 were compared. Results: Ninety-one individuals were included. A presumed causative mutation was identified in 86 individuals, of these, mutations in MECP2 in 77 individuals and mutations in SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1 or chromosome 13q in nine. Seventy-two individuals fulfilled the diagnostic criteria for classic and 12 for atypical RTT. Significant differences in early development, loss of hand use and language, intense eye gaze and the presence of early onset epilepsy were revealed in individuals with RTT according to their MECP2 genotypic status. Conclusion: Using the current diagnostic criteria, genetic and clinical variation in RTT is considerable. Significant differences between individuals with RTT with and without MECP2 mutations indicate that MECP2 is a major determinant for the clinical phenotype in individuals with RTT. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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| 22. |
- Henriksen, M. W., et al.
(författare)
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Medical Issues in Adults with Rett Syndrome–A National Survey
- 2020
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Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 23:2, s. 106-112
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine main health issues in a population of females with Rett syndrome, with a focus on individuals aged 36 or older. Methods: A national survey including 85 females, divided into a younger (1–20years), a middle (21–35years) and an older group (36–66years). Data include clinical examination, medical records and parental interviews. Prevalences of six main medical issues (scoliosis, ambulation, growth, respiration, gastrointestinal dysmobility and epilepsy) and severity scores in the three groups were compared. Results: Mean severity scores were 11.8, 15.1 and 13.7 (from younger to older), and the difference between the younger and the middle group was significant. No other major significant prevalence differences were observed. Conclusions: Most main medical issues in Rett syndrome continued to be a major concern in adulthood, but health did not seem to decline with increasing age. The results emphasize the need for clinical follow-up throughout adulthood. © 2019, © 2019 Taylor & Francis Group, LLC.
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| 23. |
- Hernández-Granados, P., et al.
(författare)
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European Hernia Society guidelines on management of rectus diastasis
- 2021
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:10, s. 1189-1191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The definition, classification and management of rectus diastasis (RD) are controversial in the literature and a variety of different surgical treatments have been described. This article reports on the European Hernia Society (EHS) Clinical Practice Guideline for RD. METHOD: The Guideline group consisted of eight surgeons. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done in November 2018 and updated in November 2019 and October 2020. Nine Key Questions (KQs) were formulated. RESULTS: Literature reporting on the definition, classification, symptoms, outcomes and treatments was limited in quality, leading to weak recommendations for the majority of the KQs. The main recommendation is to define RD as a separation between rectus muscles wider than 2 cm. A new classification system is suggested based on the width of muscle separation, postpregnancy status and whether or not there is a concomitant hernia. Impaired body image and core instability appear to be the most relevant symptoms. Physiotherapy may be considered before surgical management. It is suggested to use linea alba plication in patients without concomitant hernia and a mesh-based repair of RD with concomitant midline hernias. CONCLUSION: RD should be defined as a separation of rectus muscles wider than 2 cm and a new classification system is suggested.
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| 24. |
- Marton, Janos, et al.
(författare)
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NMR Analysis of a Series of 6,14-Ethenomorphinan Derivatives as PET Precursors and Reference Substances**
- 2021
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Ingår i: CHEMISTRYSELECT. - : Wiley. - 2365-6549. ; 6:24, s. 5994-6005
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Tidskriftsartikel (refereegranskat)abstract
- The new semisynthetic oripavine derivative 3-O-trityl-6-O-desmethyl-dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six-step procedure. This compound can be applied as precursor for the radiosynthesis of [6-O-methyl-C-11]-dihydroetorphine ([C-11]DHE). We present a detailed description of H-1 and C-13 NMR data of reference standards and precursors for [6-O-methyl-C-11]- and [6-O-(2-[F-18]fluoroethyl]orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3-O-trityl-6-O-desmethyl-phenethyl-orvinol (TDPEO) using computational methods.
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| 25. |
- Rizos, A., et al.
(författare)
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Tolerability of non-ergot oral and transdermal dopamine agonists in younger and older Parkinson’s disease patients : an European multicentre survey
- 2020
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 127:6, s. 875-879
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Tidskriftsartikel (refereegranskat)abstract
- In older patients with Parkinson’s disease (PD), the use of dopamine agonists (DA) has been limited due to uncertainties related to their tolerability in spite of potential gains with the advent of longer acting or transdermal therapies. Comparative real-life data addressing the tolerability of DA therapy across age ranges are currently sparse. This study addressed the tolerability (Shulman criteria, continued intake of DA therapy for at least 6 months) in PD patients across several European centres treated with long-acting and transdermal DA (Rotigotine skin patch, Ropinirole extended release, or Pramipexole prolonged release) as part of routine clinical care in younger and older PD patients. A medical record-based retrospective data capture and clinical interview-based follow-up survey of patients initiating or initiated on DA treatment (short and long acting) in a real-life setting. 425 cases were included [mean age 68.3 years (range 37–90), mean duration of disease 7.5 years (range 0–37), 31.5% older age (≥ 75 years of age)]. Tolerability was above 90% irrespective of age, with no significant differences between younger and older patients. Based on our findings, we suggest that long-acting/transdermal DA are tolerated in non-demented older patients, as well as in younger patients, however, with lower daily dose in older patients.
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| 26. |
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| 27. |
- Tegner, H., et al.
(författare)
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The effect of graded activity and pain education (GAPE): an early post-surgical rehabilitation programme after lumbar spinal fusion-study protocol for a randomized controlled trial
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with chronic low back pain undergoing lumbar spinal fusion (LSF) are physically inactive and thereby at risk of poor health. Barriers to being physically active need to be acknowledged in post-surgical rehabilitation. The primary objective of this randomized controlled trial (RCT) is to examine the effect of an early active intervention consisting of graded activity and pain education (GAPE) on sedentary behaviour in a population of patients undergoing LSF. The secondary objective is to examine the effect of GAPE on disability, pain, fear of movement, self-efficacy for exercise, and health-related quality of life.MethodsThe study is an RCT planned to include 144 patients undergoing LSF at 1-2 levels for low back pain caused by degeneration of the lumbar spine. The patients will be randomly assigned to receive either usual care or usual care plus GAPE. GAPE consists of nine individual physiotherapist-guided sessions over a 10-week period. The overall purpose is to reduce sedentary behaviour, by educating the patient about pain and, based on a cognitive behavioural perspective, gradually strengthen the patient's self-efficacy to be physically active and reduce fear of movement. The physiotherapist will plan the intervention in collaboration with the patient. Based on a semi-structured interview and observations of the patient in their home, they will set individually functional goals. The primary outcome will be a reduction in sedentary behaviour, measured by an accelerometer at baseline (pre-surgery) and at 3 and 12months post-surgery. Secondary outcomes will include disability, pain, fear of movement, self-efficacy for exercise, and quality of life. Secondary outcome data will be collected at baseline (pre-surgery) and at 3, 6 and 12months post-surgery.DiscussionWe hypothesize that, compared with the "usual care group", GAPE will primarily lead to a significant reduction in sedentary behaviour, and secondarily a reduction in disability, pain intensity, and fear of movement; further, it will increase the patient's self-efficacy for exercise and quality of life.Trial registrationwww.clinicaltrials.gov NCT04103970, Registered on 24 September 2019
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| 28. |
- Vester, Peter, et al.
(författare)
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Tracking structural solvent reorganization and recombination dynamics following e-photoabstraction from aqueous I-with femtosecond x-ray spectroscopy and scattering
- 2022
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 157:22
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Tidskriftsartikel (refereegranskat)abstract
- We present a sub-picosecond resolved investigation of the structural solvent reorganization and geminate recombination dynamics following 400 nm two-photon excitation and photodetachment of a valence p electron from the aqueous atomic solute, I-(aq). The measurements utilized time-resolved X-ray Absorption Near Edge Structure (TR-XANES) spectroscopy and X-ray Solution Scattering (TR-XSS) at the Linac Coherent Light Source x-ray free electron laser in a laser pump/x-ray probe experiment. The XANES measurements around the L1-edge of the generated nascent iodine atoms (I0) yield an average electron ejection distance from the iodine parent of 7.4 ± 1.5 Å with an excitation yield of about 1/3 of the 0.1M NaI aqueous solution. The kinetic traces of the XANES measurement are in agreement with a purely diffusion-driven geminate iodine-electron recombination model without the need for a long-lived (I0:e-) contact pair. Nonequilibrium classical molecular dynamics simulations indicate a delayed response of the caging H2O solvent shell and this is supported by the structural analysis of the XSS data: We identify a two-step process exhibiting a 0.1 ps delayed solvent shell reorganization time within the tight H-bond network and a 0.3 ps time constant for the mean iodine-oxygen distance changes. The results indicate that most of the reorganization can be explained classically by a transition from a hydrophilic cavity with a well-ordered first solvation shell (hydrogens pointing toward I-) to an expanded cavity around I0 with a more random orientation of the H2O molecules in a broadened first solvation shell.
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| 29. |
- Western, Benedikte, et al.
(författare)
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How many days of continuous physical activity monitoring reliably represent time in different intensities in cancer survivors
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical activity (PA) monitoring is applied in a growing number of studies within cancer research. However, no consensus exists on how many days PA should be monitored to obtain reliable estimates in the cancer population. The objective of the present study was to determine the minimum number of monitoring days required for reliable estimates of different PA intensities in cancer survivors when using a six-days protocol. Furthermore, reliability of monitoring days was assessed stratified on sex, age, cancer type, weight status, and educational level.METHODS: Data was obtained from two studies where PA was monitored for seven days using the SenseWear Armband Mini in a total of 984 cancer survivors diagnosed with breast, colorectal or prostate cancer. Participants with ≥22 hours monitor wear-time for six days were included in the reliability analysis (n = 736). The intra-class correlation coefficient (ICC) and the Spearman Brown prophecy formula were used to assess the reliability of different number of monitoring days.RESULTS: For time in light PA, two monitoring days resulted in reliable estimates (ICC >0.80). Participants with BMI ≥25, low-medium education, colorectal cancer, or age ≥60 years required one additional monitoring day. For moderate and moderate-to-vigorous PA, three monitoring days yielded reliable estimates. Participants with BMI ≥25 or breast cancer required one additional monitoring day. Vigorous PA showed the largest within subject variations and reliable estimates were not obtained for the sample as a whole. However, reliable estimates were obtained for breast cancer survivors (4 days), females, BMI ≥30, and age <60 years (6 days).CONCLUSION: Shorter monitoring periods may provide reliable estimates of PA levels in cancer survivors when monitored continuously with a wearable device. This could potentially lower the participant burden and allow for less exclusion of participants not adhering to longer protocols.
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