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| 2. |
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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 8. |
- Varela, AR, et al.
(author)
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Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity-GoPA! 2015 and 2020 Surveys
- 2023
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In: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 20:2, s. 112-128
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Journal article (peer-reviewed)abstract
- Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion.
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| 9. |
- Memon, M. A., et al.
(author)
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Aetiology and associations of halitosis : A systematic review
- 2023
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In: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 29:4, s. 1432-1438
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Research review (peer-reviewed)abstract
- Halitosis is a term that refers to an unpleasant or foul odour originating from the oral cavity that can be caused by either intra-oral or extra-oral factors. Despite the fact that halitosis has multifactorial aetiology, intra-oral factors play a significant role in the majority of cases. This systematic review assesses halitosis's intra-oral and extra-oral associations. An electronic search through MEDLINE (PubMed), Google Scholar and the Wiley Online Library was conducted to identify relevant manuscripts. A keywords-based search was performed, using the terms ‘halitosis’, ‘bad-breath’, and ‘oral malodour causes and aetiology’. Articles published from January 2014 to December 2020 were included. We selected studies evaluating the intra-oral and extra-oral factors that induce oral malodour, as well as the factors associated with systemic diseases. Eighty to ninety percent of halitosis is caused by intra-oral factors, with coated tongue, periodontal diseases and poor oral hygiene practices being the principal factors. Ten to twenty percent of halitosis is induced by extra-oral factors associated with systemic diseases. Multiple factors can cause halitosis, but most of the aetiology is intra-oral. Increased medical awareness is needed to determine the actual pathophysiological process of oral malodour in otherwise healthy individuals.
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| 10. |
- Memon, Maaz A., et al.
(author)
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Assessing salivary matrix metalloproteinase-8 in prostate cancer patients undergoing androgen deprivation therapy
- 2022
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In: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 8:5, s. 1277-1283
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Journal article (peer-reviewed)abstract
- Introduction: Matrix metalloproteinase-8 (MMP-8) is considered as one of the most promising diagnostic markers for periodontal disease. Androgen deprivation therapy (ADT) has been correlated with impaired collagen synthesis and an increase in periodontal tissue susceptibility to pathogenic microorganisms. Objective: This study aims to investigate the impact of ADT on salivary MMP-8 level and periodontal parameters, which might be useful in monitoring periodontal disease in prostate cancer patients undergoing ADT. Materials and Methods: A total of 88 subjects were selected and were divided into two groups: Group I included n = 78 PC patients who have been undergoing ADT); Group II included n = 10 healthy individuals. Periodontal parameters such as plaque index (PI), gingival index (GI), periodontal probing depth (PPD), and clinical attachment level (CAL) were examined. The salivary MMP-8 level was estimated by using the sandwich enzyme-linked immunosorbent assay method. Results: Significant differences in mean salivary MMP-8 level were found between PC patients undergoing ADT and healthy individuals. Salivary MMP-8 levels of all individuals were positively correlated with GI, PI, PPD, and CAL. Salivary MMP-8 can distinguish between periodontitis and healthy individuals with an accuracy of about 80%. Conclusion: Salivary MMP-8 levels were found to be higher in prostate cancer patients undergoing ADT compared to healthy individuals.
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| 11. |
- Agostini, Patrick, et al.
(author)
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Not-Too-Deep Channel Charting (N2D-CC)
- 2022
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In: 2022 IEEE Wireless Communications and Networking Conference (WCNC). - : IEEE. ; , s. 2160-2165
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Conference paper (peer-reviewed)abstract
- Channel charting (CC) is an emerging machine learning method for learning a lower-dimensional representation of channel state information (CSI) in multi-antenna systems while simultaneously preserving spatial relations between CSI samples. The driving objective of CC is to learn these representations or channel charts in a fully unsupervised manner, i.e., without the need for having access to explicit geographical information. Based on recent findings in deep manifold learning, this paper addresses the problem of CC via the "not-too-deep" (N2D) approach for deep manifold learning. According to the proposed approach, an embedding of the global channel chart is first learned using a deep neural network (DNN)-based autoencoder (AE), and this embedding is subsequently searched for the underlying manifold using shallow clustering methods. In this way we are able to counter the problem of collapsing extremities - a well known deficiency of channel charting methods, which in previous research efforts could only be mitigated by introducing side-information in form of distance constraints. To further exploit the ever-increasing spatio-temporal CSI resolution in modern multi-antenna systems, we propose to augment the employed AE with convolutional neural network (CNN) input layers. The resulting convolutional autoencoder (CAE) architecture is able to automatically extract sparsely distributed spatio-temporal features from beamspace domain CSI, yielding a reduced computational complexity of the resulting model.
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| 12. |
- Burke, David F., et al.
(author)
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Towards a structurally resolved human protein interaction network
- 2023
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In: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 30:2, s. 216-225
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Journal article (peer-reviewed)abstract
- Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology.
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| 13. |
- Dakhel, Ardwan, et al.
(author)
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Novel cardiovascular biomarkers associated with peripheral arterial disease in men screened for abdominal aortic aneurysm
- 2022
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In: Vasa - European Journal of Vascular Medicine. - : Hogrefe Publishing Group. - 0301-1526. ; 51:3, s. 167-173
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Journal article (peer-reviewed)abstract
- Background: Peripheral arterial disease (PAD) is a common atherosclerotic disease with severity ranging from asymptomatic to chronic limb threatening ischemia. The aim of the present cross-sectional study was to identify novel biomarkers associated with PAD. Patients and methods: Levels of 91 cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel from a cohort consisting of 267 65-year-old men recruited from a screening program for abdominal aortic aneurysm (AAA) Levels of protein biomarkers were compared in men with and without PAD (defined as an ankle brachial index of <0.9) and their diagnostic potential was calculated by receiver-operating characteristic analysis. Results: The prevalence of PAD was 14.2% (38/267). After adjustment for multiple comparisons, levels of the following 11 biomarkers remained significantly higher (p<0.0001) in patients with PAD: secretoglobin family 3A member 2, osteoprotegerin, urokinase-type plasminogen activator surface receptor, serum macrophage chemokine ligand 16, matrix metalloproteinase 9, p-selectin, growth differentiation factor 15, elafin, cystatin B, trefoil factor 3, and fatty acid-binding protein 4. Multivariable logistic regression analysis (adjusted for smoking, use of antihypertensive and lipid-lowering medication, and metformin) showed that 11 biomarkers were significantly associated with higher risk of PAD with odds ratios ranging from 1.6 to 2.4. Area under curve calculated by receiver operating characteristic curve analysis (diagnostic value) for each protein biomarker ranged from 0.63 to 0.74. Conclusions: We have identified multiple proteins with a potential to be diagnostic biomarkers for PAD, and further research is warranted to clarify their potential predictive and prognostic value.
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| 14. |
- Jansåker, Filip, et al.
(author)
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Examining the causal effect of type 2 diabetes on ischemic heart disease : - a longitudinal study with four measurements (1980-2017)
- 2023
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 198
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This longitudinal study examines a possible causal effect between type 2 diabetes and ischemic heart disease (IHD) by using measurements on four occasions from the Swedish Statistics on Income and Living Conditions (SILC) together with nationwide healthcare registers.METHODS: This was a longitudinal study based on a random sample of men and women (n = 2014) from the Swedish population with four measurements in the SILC every eight years. Baseline was 1980/81 and the participants were followed for up to 37 years. The mean age and age range at baseline were 36.5 and 20-59 years, respectively. The study used Marginal Structural Modeling (MSM-Cox) to account for time-varying exposures by implementing inverse probability weighting (IPTW). MSM-Cox with IPTW was compared with Cox proportional hazard modelling.RESULTS: The hazard ratio (HR) for IHD (369 cases) with 95% confidence interval (CI) in participants with type 2 diabetes (11.1%) compared to participants without type 2 diabetes (88.9%) was significantly higher (1.99; CI = 1.15 - 3.44) when using MSM-Cox with IPTW after adjustments for clinical and sociodemographic risk factors. When applying Cox proportional hazard models adjusted for the same variables, the HR was lower and non-significant at 1.34 (CI = 0.94 - 1.98).CONCLUSIONS: This longitudinal study with four measurements assessed a possible causal association between type 2 diabetes and IHD by applying MSM-Cox with IPTW. Although causality cannot be determined due to the remaining risk of residual bias, the results may help to elucidate a potential causal relationship between type 2 diabetes and IHD. Further causal studies on possible underlying mechanisms are, however, needed.
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| 15. |
- Khan, H. R., et al.
(author)
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Cross-cultural prevalence of sleep quality and psychological distress in healthcare workers during COVID-19 pandemic
- 2021
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In: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 11:11
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Journal article (peer-reviewed)abstract
- Background: Poor quality sleep and emotional disturbances are expected in times of crisis. COVID-19 has severely impacted healthcare worldwide and with that comes the concern about its effects on healthcare workers. The purpose of the present study was to assess sleep quality and psychological distress in healthcare workers during the COVID-19 pandemic.Methods: The present work is a multi-centric cross-sectional study targeting healthcare workers from India, Pakistan, and Nepal. It used an online version of the Pittsburg Sleep Quality Index and the General Health Questionnaire, and data were analyzed using SPSS V.24.Results: A total of 1790 participants completed the questionnaire. Of the 1790 participants, 57% reported poor sleep quality, and 10% reported a high level of psychological distress. A cross-cultural comparison found some differences between the different groups of participants. The details of the differences were further explored in the article.Conclusion: The present study highlights that a significant proportion of healthcare workers are affected by poor sleep quality and psychological distress during the COVID-19 pandemic. It also emphasizes the imperative to provide them with psychosocial support to avoid potential short- and long-term psychological consequences of these troubling times.
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| 16. |
- Li, Yanni, et al.
(author)
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Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women : A Prospective Swedish Population-Based Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Journal article (peer-reviewed)abstract
- Changes in mitochondrial DNA copy number (mtDNA-CN) and telomere length have, separately, been proposed as risk factors for various cancer types. However, those results are conflicting. Here, mtDNA-CN and relative telomere length were measured in 3225 middle-aged women included in a large population-based prospective cohort. The baseline mtDNA-CN in patients with prevalent breast cancer was significantly higher (12.39 copies/µL) than cancer-free individuals. During an average of 15.2 years of follow-up, 520 patients were diagnosed with cancer. Lower mtDNA-CN was associated with decreased risk of genital organ cancer (hazard ratio (HR), 0.84), and shorter telomere length was associated with increased risk of urinary system cancer (HR, 1.79). Furthermore, mtDNA-CN was inversely associated with all-cause (HR, 1.20) and cancer-specific mortality (HR, 1.21) when considering all cancer types. Surprisingly, shorter telomere length was associated with decreased risk of cancer-specific mortality when considering all cancer types (HR, 0.85). Finally, lower mtDNA-CN and shorter telomere length were associated with increased risk of both all-cause and cancer-specific mortality in genital organ cancer patients. In this study population, we found that mtDNA-CN and telomere length were significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer type specific and need further investigation.
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| 17. |
- Li, Yanni, et al.
(author)
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Mitochondrial heteroplasmic shifts reveal a positive selection of breast cancer
- 2023
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In: Journal of Translational Medicine. - 1479-5876. ; 21:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Breast cancer is, despite screening, not always detected early enough and is together with other tumor types known to shed genetic information in circulation. Unlike single-copy nuclear DNA, mitochondrial DNA (mtDNA) copies range from 100s to 10,000s per cell, thus providing a potentially alternative to identify potential missing cancer information in circulation at an early stage.METHODS: To characterize mitochondrial mutation landscapes in breast cancer, whole mtDNA sequencing and bioinformatics analyses were performed on 86 breast cancer biopsies and 50 available matched baseline cancer-free whole blood samples from the same individuals, selected from a cohort of middle-aged women in Sweden. To determine whether the mutations can be detected in blood plasma prior to cancer diagnosis, we further designed a nested case-control study (n = 663) and validated the shortlisted mutations using droplet digital PCR.RESULTS: We detected different mutation landscapes between biopsies and matched whole blood samples. Compared to whole blood samples, mtDNA from biopsies had higher heteroplasmic mutations in the D-loop region (P = 0.02), RNR2 (P = 0.005), COX1 (P = 0.037) and CYTB (P = 0.006). Furthermore, the germline mtDNA mutations had higher heteroplasmy level than the lost (P = 0.002) and de novo mutations (P = 0.04). The nonsynonymous to synonymous substitution ratio (dN/dS) was higher for the heteroplasmic mutations (P = 7.25 × 10 -12) than that for the homoplasmic mutations, but the de novo (P = 0.06) and lost mutations (P = 0.03) had lower dN/dS than the germline mutations. Interestingly, we found that the critical regions for mitochondrial transcription: MT-HSP1 (odds ratio [OR]: 21.41), MT-TFH (OR: 7.70) and MT-TAS2 (OR: 3.62), had significantly higher heteroplasmic mutations than the rest of the D-loop sub-regions. Finally, we found that the presence of mt.16093T > C mutation increases 67% risk of developing breast cancer. CONCLUSIONS: Our findings show that mitochondrial genetic landscape changes during cancer pathogenesis and positive selection of mtDNA heteroplasmic mutations in breast cancer. Most importantly, the mitochondrial mutations identified in biopsies can be traced back in matched plasma samples and could potentially be used as early breast cancer diagnostic biomarkers.
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| 18. |
- Li, Yanni, et al.
(author)
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Mitochondrial related genome-wide Mendelian randomization identifies putatively causal genes for multiple cancer types
- 2023
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 88
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Journal article (peer-reviewed)abstract
- BACKGROUND: Mitochondrial dysfunction is a hallmark of cancer. However, it is unclear whether it is a cause of cancer. This two-sample Mendelian randomization (MR) analyses, uses genetic instruments to proxy the exposure of mitochondrial dysfunction and cancer summary statistics as outcomes, allowing for causal inferences.METHODS: Summary statistics from 18 common cancers (2107-491,974 participants), gene expression, DNA methylation and protein expression quantitative trait loci (eQTL, mQTL and pQTL, respectively, 1000-31,684 participants) on individuals of European ancestry, were included. Genetic variants located within or close to the 1136 mitochondrial-related genes (in cis) and robustly associated with the mitochondrial molecular alterations were used as instrumental variables, and their causal associations with cancers were examined using summary-data-based MR (SMR) analyses. An additional five MR methods were used as sensitivity analyses to confirm the casual associations. A Bayesian test for colocalization between mitochondrial molecular QTLs and cancer risk loci was performed to provide insights into the potential regulatory mechanisms of risk variants on cancers.FINDINGS: We identified potential causal relationships between mitochondrial-related genes and breast, prostate, gastric, lung cancer and melanoma by primary SMR analyses. The sensitivity and the colocalization analyses further refined four genes that have causal effects on three types of cancer. We found strong evidence of positive association of FDPS expression level with breast cancer risk (OR per SD, 0.66; 95% CI, 0.49-0.83; P = 9.77 × 10-7), NSUN4 expression level with both breast cancer risk (OR per SD, 1.05; 95% CI, 1.03-1.07; P = 5.24 × 10-6) and prostate cancer risk (OR per SD, 1.06; 95% CI, 1.03-1.09; P = 1.01 × 10-5), NSUN4 methylation level with both breast and prostate cancer risk, and VARS2 methylation level with lung cancer risk.INTERPRETATIONS: This data-driven MR study demonstrated the causal role of mitochondrial dysfunction in multiple cancers. Furthermore, this study identified candidate genes that can be the targets of potential pharmacological agents for cancer prevention.FUNDING: This work was supported by Styrelsen för Allmänna Sjukhusets i Malmö Stiftelse för bekämpande av cancer (20211025).
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| 19. |
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| 20. |
- Memon, Ashfaque A, et al.
(author)
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Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women : A population-based follow-up study
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Journal article (peer-reviewed)abstract
- Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50-59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.
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| 21. |
- Memon, Ashfaque A., et al.
(author)
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Identification of novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm
- 2020
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:2, s. 132-142
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Journal article (peer-reviewed)abstract
- Aims: Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth. Methods: In this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged ≥65 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel. Results: After Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter. Conclusions: We have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.
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| 22. |
- Memon, Ashfaque A, et al.
(author)
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Mitochondrial DNA Copy Number: Linking Diabetes and Cancer
- 2022
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 37:16-18, s. 1168-1190
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Research review (peer-reviewed)abstract
- Recent Advances: Various studies have suggested that mitochondrial DNA copy number (mtDNA-CN), a surrogate biomarker of mitochondrial dysfunction, is an easily quantifiable biomarker for chronic diseases, including diabetes and cancer. However, current knowledge is limited, and the results are controversial. This has been attributed mainly to methodology and study design.Critical Issues: The incidence of diabetes and cancer has increased significantly in recent years. Moreover, type 2 diabetes (T2D) has been shown to be a risk factor for cancer. mtDNA-CN has been associated with both T2D and cancer. However, it is not known whether mtDNA-CN plays any role in the association between T2D and cancer.Significance: In this review, we have discussed mtDNA-CN in diabetes and cancer, and reviewed the literature and methodology used in published studies so far. Based on the literature review, we have speculated how mtDNA-CN may act as a link between diabetes and cancer. Furthermore, we have provided some recommendations for reliable translation of mtDNA-CN as a biomarker.Future Directions: Further research is required to elucidate the role of mtDNA-CN in the association between T2D and cancer. If established, early lifestyle interventions, such as physical activity and diet control that improve mitochondrial function, may help preventing cancer in patients with T2D.
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| 23. |
- Nymberg, Peter, et al.
(author)
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Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women : a population-based cohort study
- 2021
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 52:1, s. 148-157
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Journal article (peer-reviewed)abstract
- Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. To examine the association between mtDNA-CN and incident VTE among middle-aged women. 6917 women aged 50-64 years, followed for 20 years in the Women's Health In the Lund Area (WHILA) study. DNA samples for mtDNA quantification were available from 2521 women. Quantification of mtDNA-CN was performed using a well-optimized droplet digital PCR method. After exclusions of women with anticoagulant treatment, women living in nursing homes, and women who were diagnosed with cancer, stroke, VTE, or coronary heart disease at baseline, a cohort of 2117 women remained for analysis. Cox regression was used to analyze the relationship between mtDNA-CN and time to VTE (hazard ratio = HR). In total, 87 women were diagnosed with VTE during follow-up, corresponding to an incidence rate of 2.8 per 1000 person-years. Neither crude nor adjusted HR for mtDNA-CN were significantly associated with incident VTE. A sensitivity analysis with inclusion of excluded women did not change the results. MtDNA-CN was not significantly associated with VTE. The present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, should not be considered a biomarker that plays a major role for developing VTE. However, due to limited study size we may not exclude minor associations.
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| 24. |
- Pirkis, Jane, et al.
(author)
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Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends : An interrupted time series analysis in 33 countries
- 2022
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 51
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Journal article (peer-reviewed)abstract
- Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age-and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Copyright (C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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| 25. |
- Roumans, Sanne, et al.
(author)
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Association of circulating let-7b-5p with major depressive disorder : a nested case-control study
- 2021
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 21:1, s. 1-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD.METHODS: In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women's Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression.RESULTS: Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12-0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2-5 years from baseline).CONCLUSIONS: These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD.
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| 26. |
- Sundquist, Kristina, et al.
(author)
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Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women
- 2022
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In: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 9
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Journal article (peer-reviewed)abstract
- Heart failure (HF) is a leading cause of death in both men and women. However, risk factors seem to differ for men and women and significant gaps in sex-specific knowledge exist. Mitochondria are critical for cardiomyocytes and in this study, we investigated the role of baseline mitochondrial DNA copy number (mtDNA-CN) in HF incidence in middle-aged women and its possible role in the association between myocardial infarction (MI) and HF. Finally, we also investigated whether baseline mtDNA-CN was associated with overall and HF mortality. Baseline levels of mtDNA-CN were quantified by droplet digital PCR in a population-based follow-up study of middle-aged (50-59 years) Swedish women (n = 2,508). The median follow-up period was 17 years. Levels of mtDNA-CN were associated with age, BMI, alcohol, smoking, education, physical activity and lipid biomarkers. Multivariable Cox regression analysis adjusted for potential confounders showed that each standard deviation decrease of baseline mtDNA-CN was associated with higher incidence of HF (HR = 1.34; 95% CI=1.11-1.63). Similar results were obtained when mtDNA-CN levels were categorized into quartiles with lowest vs. highest quartile showing the highest risk of HF incidence (HR = 2.04 95% CI=1.14; 3.63). We could not detect any role of mtDNA-CN in the association between MI and HF incidence. Lower baseline mtDNA-CN levels were associated with both overall (HR = 1.27; 95% CI=1.10-1.46) and HF mortality (HR = 1.93; 95% CI=1.04-3.60); however, in multivariable analysis adjusted for potential confounders, the higher risks of HF mortality were no longer significant (HR=1.57; 95% CI=0.85-2.90). In conclusion, low baseline mtDNA-CN is an easily quantifiable molecular risk factor for HF incidence and may be a risk factor for overall and HF-related mortality.
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| 27. |
- Sundquist, Kristina, et al.
(author)
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Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases : A study on suspected cancer patients
- 2020
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In: Molecular Carcinogenesis. - : Wiley. - 1098-2744 .- 0899-1987. ; 59:12, s. 1362-1370
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Journal article (peer-reviewed)abstract
- Circulating cell-free nuclear DNA (nDNA) has been implicated in individual cancer types with a diagnostic value; however, the role of cell-free mitochondrial DNA (mtDNA) in cancers is controversial. We aimed to investigate and compare the diagnostic potential of both nDNA and mtDNA for multiple cancers and to investigate their ability to distinguish multiple cancers from healthy controls and from nonmalignant diseases. We also investigated the prognostic value of both nDNA and mtDNA. The absolute copy number of circulating DNAs in suspected cancer patients (n = 286) referred to a cancer diagnostic center and healthy controls (n = 109) was quantified by droplet digital polymerase chain reaction. Among the suspected cancer patients, 66 (23%) were diagnosed with various cancers, 193 (67%) with nonmalignant diseases, and 27 (10%) with no active disease. Levels of nDNA were significantly higher in cancers (copies/μl; mean ± SD, 21.0 ± 14.2) as compared with nonmalignant diseases (15.2 ± 10.0) and controls (9.3 ± 4.1). In contrast, levels of mtDNA were significantly lower in cancers (copies/μl; mean ± SD, 68,557 ± 66,663) and nonmalignant diseases (60,174 ± 55,831) as compared with controls (98,714 ± 77,789). Receiver operating curve analysis showed that nDNA not only could distinguish multiple cancers from controls (area under curve [AUC] = 0.78; 95% confidence interval [CI] = 0.70-0.86) but also from nonmalignant diseases (AUC = 0.68; 95% CI = 0.59-0.76). However, mtDNA could only differentiate cancers from controls (AUC = 0.65; 95% CI = 0.56-0.73). Higher levels of nDNA were also associated with increased mortality in the cancer patients (hazard ratio = 2.3; 95% CI = 1.1-4.7). Circulating cell-free nDNA, but not the mtDNA, could distinguish multiple cancers from nonmalignant diseases and was associated with poor survival of cancer patients.
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| 28. |
- Sundquist, Kristina, et al.
(author)
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Elucidating causal effects of type 2 diabetes on ischemic heart disease from observational data on middle-aged Swedish women : a triangular analytical approach
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Journal article (peer-reviewed)abstract
- The association between type 2 diabetes (T2D) and ischemic heart disease (IHD) is well established but the potential causal association needs further studying. In an attempt to elucidate the causal effect of T2D on IHD, we used three different analytical approaches in two different datasets. A well-defined cohort of 6047 women aged 50–59 years were included at baseline (1995 to 2000) and followed until 2015 for IHD. The median follow-up was 16.3 years. We used a Marginal Structural Cox model (MSM Cox) to account for time-varying exposure (time at onset of T2D) and for ten confounders (using inverse probability weighting, IPW). We also compared the MSM-Cox models with traditional Cox regression modelling in the cohort. Finally, we analyzed information on individuals from Swedish population-based registers with national coverage in a comprehensive co-relative design and extrapolated the results to MZ twins. The Hazard Ratio (HR) for IHD in relation to T2D at baseline and T2D occurring during the follow-up in the MSM Cox model weighted by IPW (based on the ten included confounders) was 1.43 (95% confidence interval [CI] 1.07–1.92). The corresponding HR from the traditional Cox regression model was of similar effect size. The average extrapolated MZ twin estimate from our co-relative model was 1.61 (95% CI 1.48–1.86). Our findings, based on a triangular approach, support the existence of a causal association between T2D and IHD and that preventive long-term measures in order to avoid or postpone IHD should include monitoring and treatment of both the T2D itself as well as other cardiovascular risk factors.
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| 29. |
- Sundquist, Kristina, et al.
(author)
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Inflammatory proteins and miRNA-144-5p in patients with depression, anxiety, or stress- and adjustment disorders after psychological treatment
- 2021
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In: Cytokine. - : Elsevier BV. - 1043-4666. ; 146
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Journal article (peer-reviewed)abstract
- Both inflammatory proteins and microRNAs (miRNA) have been reported to be associated with various psychiatric disorders. However, the association between inflammatory proteins and miRNAs remains largely unknown, especially for patients with depression, anxiety, or stress- and adjustment disorders. In this study, we analyzed plasma levels of 92 inflammatory proteins from 178 patients with depression, anxiety, or stress- and adjustment disorders at baseline and after 8-week psychological treatments which resulted in a significant decrease in the Montgomery Åsberg Depression Rating Scale (MADRS-S) score. We investigated the response of the proteins after treatment and the correlation with miR-144-5p. After Benjamini-Hochberg correction for multiple testing, a total of 36 inflammatory proteins changed significantly after 8-week psychological treatments. Among the 36 significantly changed proteins, 21 proteins showed a decrease, and 17/21 proteins were inversely associated with plasma miR-144-5p levels at baseline. In addition, decreases in these proteins were associated with increases in miR-144-5p after treatment. The findings were similar after stratification by use of medications. The associations between the proteins and depression at baseline, measured by MADRS-S, as well as the change in protein levels and treatment response were, however, less clear. These findings need to be examined in future studies.
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| 30. |
- Sundquist, Kristina, et al.
(author)
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Macrophage Migration Inhibitory Factor as a Predictor for Long-term Improvements After Mindfulness-Based Group Therapy or Treatment as Usual for Depression, Anxiety or Stress and Adjustment Disorders
- 2020
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In: Mindfulness. - : Springer Science and Business Media LLC. - 1868-8527 .- 1868-8535. ; 11:6, s. 1370-1377
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Journal article (peer-reviewed)abstract
- Objectives: Identification of biological markers that can guide treatment selection is considered to be a viable solution for personalized treatment for patients with psychiatric disorders. This study investigated whether macrophage migration inhibitory factor (MIF) levels at baseline were associated with mindfulness-based group therapy or cognitive behavioral therapy response in patients with mild to moderate symptoms of depression, anxiety, or stress- and adjustment disorders. Methods: A total of 168 patients (aged 21–65 years) with psychiatric disorders were included from a randomized controlled trial. Plasma MIF levels in all the patients were analyzed using Luminex assay. Results: Higher MIF levels at baseline were significantly associated with better long-term (1-year follow-up) improvement in psychiatric symptoms, as measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS-S), compared with lower MIF levels, after adjustment for baseline MADRS-S score, age, sex, BMI, and pharmacotherapy (β = 5.89, p = 0.001). Patients with higher levels of MIF (8235–23,391 pg/ml) had an almost 6 points’ larger decrease in MADRS-S score after 1 year compared with those with lower MIF (727–8223 pg/ml) at baseline. Similar trends were seen after 8 weeks, albeit non-significant (β = 1.99, p = 0.18). Conclusions: The findings indicate that higher plasma MIF levels at baseline may predict better long-term outcomes with psychotherapeutic interventions for mild to moderate symptoms of depression, anxiety, or stress and adjustment disorders. MIF levels may serve as a potential biomarker that can guide treatment selection for the personalized treatment for patients with psychiatric disorders.
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| 31. |
- Sundquist, Kristina, et al.
(author)
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Role of mitochondrial DNA copy number in incident cardiovascular diseases and the association between cardiovascular disease and type 2 diabetes : A follow-up study on middle-aged women
- 2022
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In: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 341, s. 58-62
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate biomarker of mitochondrial dysfunction and is associated with type 2 diabetes (T2D) and cardiovascular disease (CVD). However, despite being associated with both CVD and T2D, it is not known what role mtDNA-CN has in the association between T2D and CVD. Our aims were to investigate whether, (1) baseline mtDNA-CN is associated with CVD incidence and (2) mtDNA-CN has a role as a mediator between T2D and CVD.METHOD: We quantified absolute mtDNA-CN by droplet digital PCR method in a population-based follow-up study of middle aged (52-65 years) women (n = 3062). The median follow-up period was 17 years.RESULTS: Our results show that low baseline levels of mtDNA-CN (<111 copies/μL) were associated with an increased risk of CVD (HR = 1.32, 95% CI = 1.08; 1.63) as well as with specific CVDs: coronary heart disease (HR = 1.28, 95% CI = 0.99; 1.66), stroke (HR = 1.26, 95% CI = 0.87; 1.84) and abdominal aortic aneurysm (HR = 2.61, 95% CI = 1.03; 6.62). The associations decreased but persisted even after adjustment for potential confounders. Furthermore, our results show that the total effect of T2D on future risk of CVD was reduced after controlling for mtDNA-CN and the proportion mediated by mtDNA-CN was estimated to be 4.9%.CONCLUSIONS: Lower baseline mtDNA-CN is associated with incident CVD and may have a mediating effect on the association between T2D and CVD; however, this novel observation needs to be confirmed in future studies.
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| 32. |
- Vats, Sakshi, et al.
(author)
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Associations of global DNA methylation and homocysteine levels with abdominal aortic aneurysm : A cohort study from a population-based screening program in Sweden
- 2020
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 321, s. 137-142
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Journal article (peer-reviewed)abstract
- Abdominal aortic aneurysm (AAA) is a life-threatening condition with a mortality rate of over 80%. Persistent smoking, which is a risk factor for AAA, has lasting effects on DNA methylation. Moreover, a plasma-amino acid, homocysteine, previously implicated in vascular diseases, including aneurysms, has well-established biological association with methylation. In the present study, we aimed to determine the global DNA methylation, homocysteine levels and their association with AAA and its growth. Enzyme-linked immunosorbent assay (ELISA) was used to quantify global DNA methylation in whole blood-DNA samples and diagnostic enzymatic assay quantified plasma homocysteine, from 65-year old men with (n = 116) and without AAA (n = 230) diagnosed at ultrasound screening. We found significantly higher global DNA methylation (p < .001) and homocysteine levels (p < .001) in men with AAA compared to those without AAA, and direct linear associations with baseline aortic diameter. On multivariable regression analysis, global DNA methylation (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and homocysteine levels (OR: 1.1; 95% CI:1.0-1.1) were positively associated with AAA, independent of smoking, medication use, and major co-morbidities. However, we did not find any significant association between DNA methylation or homocysteine levels with AAA growth during follow-up. We found that global DNA methylation and homocysteine levels are higher in men with AAA but are not associated with AAA growth. This indicates that different pathways and mechanisms may be involved in initiation and progression of AAA. More studies are needed to understand the precise role of DNA methylation, homocysteine and their interplay in AAA pathophysiology.
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| 33. |
- Vats, Sakshi, et al.
(author)
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Characterization of the Mitochondrial Genetic Landscape in Abdominal Aortic Aneurysm
- 2023
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In: Journal of the American Heart Association. - 2047-9980. ; 12:8
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Journal article (peer-reviewed)abstract
- Background: Abdominal aortic aneurysm (AAA) is a vascular disease with a mortality rate of >80% if ruptured. Mitochondrial dysfunction has been previously implicated in AAA pathogenesis. In this study, we aimed to characterize the mitochondrial genetic landscape in AAA.Methods and Results: Whole mitochondrial genome sequencing and bioinformatics analysis were performed in comorbidity matched 48 cases without AAA and 48 cases with AAA, objectively diagnosed, and selected from a cohort of 65‐year‐old men recruited for a screening program. We identified differential mutational landscapes in men with and without AAA, with errors in mitochondrial DNA replication or repair as potential sources. Heteroplasmic insertions and overall heteroplasmy of structural rearrangements were significantly elevated in AAA cases. Three heteroplasmic variants were associated with risk factors of AAA: leukocyte concentration, plasma glucose, and cholesterol levels, respectively. Interestingly, mutations were more prevalent in regulatory part of the mitochondria, the displacement loop region, in AAA as compared with controls (P value <0.05), especially in the conserved and critical mitochondrial extended termination‐associated sequence region. Moreover, we report a novel 24 bp mitochondrial DNA duplication present exclusively in cases with AAA (4%) and 75% of the unmatched AAA biopsies. Finally, the haplogroup cluster JTU was overrepresented in AAA and significantly associated with a positive family history of AAA (odds ratio, 2.9 [95% CI, 1.1–8.1]).Conclusions: This is the first study investigating the mitochondrial genome in AAA, where important genetic alterations and haplogroups associated with AAA and clinical risk factors were identified. Our findings have the potential to fill in gaps in the missing genetic information on AAA.
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| 34. |
- Vats, Sakshi, et al.
(author)
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Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm : a Swedish population-based retrospective cohort study
- 2024
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In: European Journal of Preventive Cardiology. - 2047-4881. ; 31:1, s. 61-74
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Journal article (peer-reviewed)abstract
- AIMS: The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible.METHODS AND RESULTS: The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05).CONCLUSIONS: Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.
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| 35. |
- Wang, Xiao, et al.
(author)
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Association of Circulating Long Noncoding 7S RNA with Deep Vein Thrombosis
- 2023
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In: Seminars in Thrombosis and Hemostasis. - 1098-9064. ; 49:7, s. 702-708
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Journal article (peer-reviewed)abstract
- Mitochondrial dysfunction is a recognized factor in the pathogenesis of deep vein thrombosis (DVT). The role of 7S RNA, a long noncoding RNA that plays an important role in mitochondrial function, in DVT remains unclear. In this study, we aimed to investigate the potential use of 7S RNA as a biomarker in DVT. Plasma samples were obtained from 237 patients (aged 16-95 years) with suspected DVT recruited in a prospective multicenter management study (SCORE) where 53 patients were objectively confirmed with a diagnosis of DVT and the rest were diagnosed as non-DVT. 7S RNA was measured using quantitative real-time polymerase chain reaction in plasma samples. The plasma expression of 7S RNA was significantly lower in DVT compared with non-DVT (0.50 vs. 0.95, p = 0.043). With the linear regression analysis, we showed that the association between the plasma expression of 7S RNA and DVT (β = -0.72, p = 0.007) was independent of potential confounders. Receiver-operating characteristic curve analysis showed the area under the curve values of 0.60 for 7S RNA. The findings of the present study showed a notable association between 7S RNA and DVT. However, further investigations are needed to fully elucidate the exact role of 7S RNA in the pathophysiology of DVT and its diagnostic value.
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| 36. |
- Wang, Xiao, et al.
(author)
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Circulating mitochondrial long non-coding 7S RNA in primary health care patients with depression/anxiety
- 2024
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In: Journal of Affective Disorders. - 0165-0327. ; 349, s. 101-106
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Journal article (peer-reviewed)abstract
- BACKGROUND: The significant role of long non-coding 7S RNA in controlling mitochondrial transcription highlights its importance in mitochondrial function. Considering the suggested connection between mitochondrial dysfunction and the onset of mental disorders, this study aimed to explore the potential involvement of 7S RNA in the context of depression/anxiety.RESULTS: A total of 181 patients in primary health care (age 20-64 years) with depression/anxiety and 59 healthy controls were included in the study. 7S RNA was measured using quantitative real-time PCR in plasma samples collected before (baseline) and after 8 weeks of treatment (mindfulness or cognitive-based behavioral therapy). Upon adjustment for age and sex, the baseline plasma levels of 7S RNA were significantly higher in patients than in healthy controls (p < 0.001). Notably, post-treatment, there was a significant reduction in 7S RNA levels (p = 0.03). These changes in 7S RNA were related to the treatment response, as indicated by HADS-D (Hospital Anxiety and Depression Scale) scores (ß = -0.04, p = 0.04), even after accounting for baseline scores and other cofounders.CONCLUSION: The findings of this study indicate an association between plasma 7S RNA levels and depression/anxiety, as well as treatment response. While further confirmatory analyses are necessary, plasma 7S RNA holds promise as a potential predictive biomarker for both depression/anxiety and the treatment response within these disorders.
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| 37. |
- Wang, Xiao, et al.
(author)
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Role of multiple risk factors in mental disorders diagnosed in middle-aged women : A population-based follow-up study
- 2022
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In: Journal of Psychiatric Research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 156, s. 414-421
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Journal article (peer-reviewed)abstract
- The aims of the study were 1). to investigate the association between the potential risk factors including socio-demographic, lifestyle and DNA methylation and mental disorders in middle-aged women from a large population-based follow-up study, and 2). to estimate the risk score by combining the potential risk factors to examine the mental disorder's incidence. A total of 6461 women, aged 50-65 years, were included in the study. After a median follow-up of 17 years, 2026 (31%) women were diagnosed with mental disorders. The association between these factors and the risk of mental disorders was analyzed using Cox regression models. Harrell's concordance index (C-index) was used to quantify models' predictive performance for future mental disorders. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. We found that smoking (HR = 1.38, 95% CI: 1.24-1.54), less physical activity (HR = 1.33, 95% CI: 1.10-1.60), being single (HR = 1.16, 95% CI: 1.04-1.29) and unemployment (HR = 1.50, 95% CI: 1.33-1.70) were independently associated with an increased risk of overall mental disorders. Risk score models combining all these observed factors showed an increased risk, but the prediction ability was low, except for the risk of alcohol use disorders (AUD) and drug use disorders (DUD) (C-index = 0.8). Finally, women who developed MDD/anxiety during follow-up had significantly higher global DNA methylation at baseline than women who did not develop MDD/anxiety (p = 0.005). In conclusion, our results indicate that the studied risk factors were associated with mental disorders in a type-specific manner. The predictive model showed that smoking, alcohol consumption, education and physical activity may predict future AUD/DUD. Global DNA methylation may be a potential risk factor for MDD/anxiety incidence.
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| 38. |
- Wang, Xiao, et al.
(author)
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The Association between Blood-Based Global DNA Methylation and Venous Thromboembolism
- 2021
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In: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 47:6, s. 662-668
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Journal article (peer-reviewed)abstract
- Alterations in DNA methylation patterns have been associated with many diseases. However, the role of DNA methylation in venous thromboembolism (VTE) is not well established. The aim of this study was to investigate a possible association between global DNA methylation and VTE. The study participants consisted of 168 individuals including 74 patients with primary VTE from the Malmö Thrombophilia Study (MATS) and 94 healthy controls. Among 74 primary VTE patients, 37 suffered VTE recurrence during the follow-up period; 37 nonrecurrent VTE patients were included for comparison. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. Global DNA methylation was significantly higher in primary VTE patients compared with the healthy controls (median: 0.17 vs. 0.08%; p < 0.001). After stratification of data from primary VTE patients according to sex, the association between higher global DNA methylation and shorter recurrence-free survival time was of borderline statistical significance in males (β = -0.2; p = 0.052) but not in females (β = 0.02; p = 0.90). Our results show that global DNA methylation is associated with primary VTE and that higher levels of global DNA methylation may be associated with early VTE recurrence in males but not in females. Further investigation on the role of DNA methylation as a diagnostic or preventive biomarker in VTE is warranted.
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| 39. |
- Wang, Xiao, et al.
(author)
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The association of mitochondrial DNA copy number with incident mental disorders in women : A population-based follow-up study
- 2022
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 308, s. 111-115
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Available evidence suggests that mitochondrial DNA copy number (mtDNA-CN) may differ among patients with mental disorders compared to the general population. However, whether mtDNA-CN is independently associated with the subsequent incidence of mental disorders remains unclear.MATERIAL AND METHODS: We used droplet digital PCR to measure the absolute mtDNA-CN in DNA samples obtained from a population-based follow-up study, which included a total of 2354 middle-aged women (52-63 years) who were free of mental disorders at baseline. After 17 years (median) of follow-up, 727 participants were diagnosed with mental disorders.RESULTS: In the univariate Cox regression, lower baseline mtDNA-CN (mtDNA-CN < 117) was associated with a higher risk of mental disorders (HR = 1.16, p = 0.047). In addition, smoking, marital status and sleeping quality were associated with both mtDNA-CN and mental disorders. After adjusting for these variables, the association between mtDNA-CN and mental disorders decreased and became non-significant (HR = 1.07, p = 0.36). Stratification of data according to the subtype of mental disorders, showed that low mtDNA-CN was associated with a higher risk of alcohol or drug use disorders (HR = 1.82, p = 0.045 after adjusting).CONCLUSION: In the present study, we could not find any independent association between mtDNA-CN blood and the most common mental disorders in a population-based follow-up study of Swedish women, except for alcohol and drug use disorders. The use of blood mtDNA-CN as a biomarker of mental disorders, in addition to other risk factors, needs to be further examined in future studies.
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| 40. |
- Wang, Xiao, et al.
(author)
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The association of zonulin-related proteins with prevalent and incident inflammatory bowel disease
- 2022
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In: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 22:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Current evidence regarding the association of serum zonulin-related proteins (ZRP) levels with prevalent inflammatory bowel disease (IBD) is contradictory. Moreover, the association with the subsequent risk of incident IBD is still unexplored. This study aimed to investigate the association of serum ZRP levels with both prevalent and incident IBD.METHOD: The study included a total of 130 women (51-61 years) from the Women's Health in Lund Area (WHILA) study, which included 18 prevalent IBD (diagnosed before baseline) and 47 incident IBD diagnosed during the 17 years (median) follow-up and age- and sampling time-matched controls. Serum ZRP was tested in all participants by ELISA.RESULTS: The serum ZRP levels were significantly higher in prevalent IBD compared to their matched controls (63.2 ng/ml vs 57.0 ng/ml, p = 0.02), however, no evidence of a difference in ZRP levels was found between the women who developed IBD during the follow-up period and their matched controls (61.2 ng/ml vs 59.7 ng/ml, p = 0.34). Using linear mixed models, we found that the association between serum ZRP levels and prevalent IBD (β = 6.2, p = 0.01), remained after adjusting for potential confounders. Conditional logistic regression models showed no evidence of an association between ZRP level and incident IBD (OR 1.03, p = 0.34).CONCLUSION: Higher serum ZRP levels were associated with prevalent IBD, but not with incident IBD in our study samples.
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