| 1. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 2. |
- Christensen, Mette M H, et al.
(författare)
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The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c
- 2011
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 21:12, s. 837-850
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac). less thanbrgreater than less thanbrgreater thanMethod The South Danish Diabetes Study was a 2 x 2 x 2 factorial, prospective, randomized, double-blind, placebo-controlled, multicentre study. One hundred and fifty-nine patients received 1 g of metformin, twice daily continuously, and 415 repeated plasma metformin measurements were obtained after 3, 6, and 9 months of treatment. less thanbrgreater than less thanbrgreater thanResults The mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54-4133 ng/ml, rho = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001). The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months. less thanbrgreater than less thanbrgreater thanConclusion In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous 80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.
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| 3. |
- Fachmann, Mette S. R., et al.
(författare)
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Cost-effective optimization of real-time PCR-based detection of Campylobacter and Salmonella with inhibitor tolerant DNA polymerases
- 2015
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Ingår i: Journal of Applied Microbiology. - : Blackwell Publishing Ltd. - 1364-5072 .- 1365-2672. ; 119:5, s. 1391-1402
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to cost-effectively improve detection of foodborne pathogens in PCR inhibitory samples through the use of alternative DNA polymerases. Methods and Results: Commercially available polymerases (n = 16) and PCR master mixes (n = 4) were screened on DNA purified from bacterial cells in two validated real-time PCR assays for Campylobacter and Salmonella. The five best performing (based on: limit of detection (LOD), maximum fluorescence, shape of amplification curves and amplification efficiency) were subsequently applied to meat and faecal samples. The VeriQuest qPCR master mix performed best for both meat and faecal samples (LODs of 102 and 104 CFU ml-1 in the purest and crudest DNA extractions respectively) compared with Tth (LOD = 102-103 and 105-106 CFU ml-1). AmpliTaqGold and HotMasterTaq both performed well (LOD = 102-104 CFU ml-1) with meat samples and poorly (LOD = 103-106 CFU ml-1/not detected) with faecal samples. Conclusions: Applying the VeriQuest qPCR master mix in the two tested real-time PCR assays could allow for simpler sample preparation and thus a reduction in cost. Significance and Impact of the Study: This work exemplifies a cost-effective strategy for optimizing real-time PCR-based assays. However, a DNA polymerase suitable for one assay and sample type is not necessarily optimal for other assays or sample types.
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| 4. |
- Gedebjerg, Anne, et al.
(författare)
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CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1037-1045
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, alone or in combination with C-peptide, a marker of hyperinsulinemia/ insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We com-puted adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. RESULTS During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07–1.96]) and with even greater risk of all-cause mortality (2.47 [1.88–3.25]). Compared with patients with low hs-CRP (£3 mg/L) and low C-peptide (<1,470 pmol/L), those with high lev-els of both biomarkers had the highest CVE (1.61 [1.10–2.34]) and all-cause mortality risk (2.36 [1.73–3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. CONCLUSIONS The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker sup-ports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.
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| 5. |
- Jacobsen, Carsten Suhr, et al.
(författare)
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Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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| 6. |
- Jorgensen, Mette Rose, et al.
(författare)
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Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects : A randomized, double-blind placebo-controlled, cross-over trial
- 2016
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Ingår i: Acta Odontologica Scandinavica. - : Informa Healthcare. - 0001-6357 .- 1502-3850. ; 74:5, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. Materials and methods: The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables Results: Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported Conclusions: Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects
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| 7. |
- Nielsen, Alex Christian Yde, et al.
(författare)
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Gastroenteritis and the novel picornaviruses aichi virus, cosavirus, saffold virus, and salivirus in young children
- 2013
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 57:3, s. 239-242
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Tidskriftsartikel (refereegranskat)abstract
- Background: During the last few years many new human picornaviruses have been discovered due to advances in metagenomics and other molecular biological approaches. The clinical significance and the occurrence are only sparsely described. Objectives: To determine the epidemiology and clinical significance of infections with the novel human picornaviruses, aichi virus, cosavirus, salivirus, and saffold virus in infants in Denmark. Study design: We tested 1393 stool samples from a birth cohort of 454 children for these viruses. Samples were collected at ages 6, 10 and 15 months, and at episodes of gastroenteritis. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays. Each study participant had a diary, where the parents reported episodes of disease, including gastroenteritis. Results: Aichi virus, salivirus and saffold virus were detected in 6, 9 and 38 of the children, respectively, but cosavirus was not detected in any of the children. There was a clear seasonal variation with most infections occurring in autumn and winter. A statistically significant association between the findings of salivirus and gastrointestinal disease was demonstrated. There was no association between gastrointestinal disease and the presence of aichi virus or saffold virus. Conclusions: The newly discovered human picornaviruses aichi virus, saffold virus, and salivirus are circulating in Danish children, with the most common being saffold virus. Saffold virus was seen almost exclusively in the autumn and winter period. Salivirus was the only virus, which was significantly associated with gastroenteritis, although the number of positive samples was rather low. (C) 2013 Elsevier B. V. All rights reserved.
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| 8. |
- Nielsen, Mette Lykke, et al.
(författare)
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New forms of work among young people: Implications for the working environment.
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Changes in the labor marked globally and in the Nordic countries involve new forms of work and atypical employment among young workers. A significant proportion of young workers are in temporary positions, working irregular working hours, and part-time work. This also applies to the young workers portrayed in this report. They are working at online platforms as e-sport gamers, YouTuber or Influencers, an thus move into the borderland of the meanings we usually ascribe to the categories ‘work’ and ‘working environment’. This development also apply to traditional professions, such as carpentry work or service work, but the new aspect is that the work is mediated through online platforms, which seems to affect the working environment for those young workers. It is important to know more about new employment forms if we are to improve working environment among these young workers.
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| 9. |
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| 10. |
- Risum, Malene, et al.
(författare)
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Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis : A Pre and Post-Intervention Analysis
- 2020
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Ingår i: JOURNAL OF FUNGI. - : MDPI. - 2309-608X. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.
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