| 1. |
- Adamsson, Viola, et al.
(författare)
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Effects of a Nordic diet on cardiovascular and metabolic risk factors in hypercholesterolemic subjects: a randomized controlled study
- 2009
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Konferensbidrag (refereegranskat)abstract
- Background: Apart from lipid-lowering drugs, dietary changes can also reduce plasma LDL-C concentrations. No studies have been conducted to investigate the clinical effects of a diet with traditional foods originating from the Nordic countries. Method: In a randomised, controlled parallel-group intervention study 88 mildly hypercholesterolemic men and women were randomized to either an ad libitum Nordic diet (ND) or a control diet (CD) for 6 weeks. All meals and foods were provided to the participants in the ND group. Primary outcome measure was LDL-cholesterol, and secondary outcomes were blood pressure, plasma insulin and glucose concentrations. The ND was a high-fibre diet rich in plant foods (fruit, berries, vegetables, root vegetables, whole grain cereals and legumes), vegetable fats (rapeseed oil and nuts) and fatty fish, low-fat milk products, but low in salt, added sugars, saturated fats and red meats. Result: 86 subjects completed the study. Distribution of carbohydrates, fat and protein (E%) in ND was 54, 27, 19, respectively. ND lowered plasma total cholesterol 0.98±0.75 mmol/l (-16%), LDL-C by 0.83±0.67 mmol/l (-21%), HDL-C 0.08±0.23 mmol/l (-5%), including reduced LDL/HDL ratio by -0.42±0.57 (-14%) (all p<0.01 versus controls). Insulin concentrations decreased by 0.51± 2.25 (-9%, p=0.01) and systolic blood pressure by 7±13 mmHg (-5%, P<0.01) compared to controls. Despite diets were eaten ad libitum, body weight decreased by 3.0 kg in the ND (P<0.001). No significant differences were found for diastolic blood pressure, triglycerides or plasma glucose. Conclusion: A Nordic diet improves blood lipid profile, and insulin sensitivity as well as lowering blood pressure to a clinically significant extent in hypercholesterolemic subjects.
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| 2. |
- Genshaft, Alex S., et al.
(författare)
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Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction
- 2016
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- We present a scalable, integrated strategy for coupled protein and RNA detection from single cells. Our approach leverages the DNA polymerase activity of reverse transcriptase to simultaneously perform proximity extension assays and complementary DNA synthesis in the same reaction. Using the Fluidigm C1 (TM) system, we profile the transcriptomic and proteomic response of a human breast adenocarcinoma cell line to a chemical perturbation, benchmarking against in situ hybridizations and immunofluorescence staining, as well as recombinant proteins, ERCC Spike-Ins, and population lysate dilutions. Through supervised and unsupervised analyses, we demonstrate synergies enabled by simultaneous measurement of single-cell protein and RNA abundances. Collectively, our generalizable approach highlights the potential for molecular metadata to inform highly-multiplexed single-cell analyses.
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| 3. |
- Sällman Almén, Markus, et al.
(författare)
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Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.
- 2013
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Background:The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index.Methods:In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD).Results:The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012).Conclusions:This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.
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| 4. |
- Askar, Raad, et al.
(författare)
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Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
- 2020
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBuprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS.ResultsThe area under the time concentration curve (AUC0-t) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008).ConclusionsThe lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability.
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| 5. |
- Caruso, Vanni, et al.
(författare)
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mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts
- 2016
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 581:2, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.
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| 6. |
- Darmanis, Spyros, et al.
(författare)
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ProteinSeq : high-performance proteomic analyses by proximity ligation and next generation sequencing
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9, s. e25583-
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Tidskriftsartikel (refereegranskat)abstract
- Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 μl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use.
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| 7. |
- Darmanis, Spyros, et al.
(författare)
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Simultaneous Multiplexed Measurement of RNA and Proteins in Single Cells
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 14:2, s. 380-389
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Tidskriftsartikel (refereegranskat)abstract
- Significant advances have been made in methods to analyze genomes and transcriptomes of single cells, but to fully define cell states, proteins must also be accessed as central actors defining a cell's phenotype. Methods currently used to analyze endogenous protein expression in single cells are limited in specificity, throughput, or multiplex capability. Here, we present an approach to simultaneously and specifically interrogate large sets of protein and RNA targets in lysates from individual cells, enabling investigations of cell functions and responses. We applied our method to investigate the effects of BMP4, an experimental therapeutic agent, on early-passage glioblastoma cell cultures. We uncovered significant heterogeneity in responses to treatment at levels of RNA and protein, with a subset of cells reacting in a distinct manner to BMP4. Moreover, we found overall poor correlation between protein and RNA at the level of single cells, with proteins more accurately defining responses to treatment.
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| 8. |
- Gudmundsdottir, K. K., et al.
(författare)
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Decentralising atrial fibrillation screening to overcome socio-demographic inequalities in uptake in STROKESTOP II
- 2021
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 28:1, s. 3-9
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Tidskriftsartikel (refereegranskat)abstract
- Objective In the first STROKESTOP atrial fibrillation screening study, participation was influenced by socio-demographic and geographic factors. To improve uptake in the second study, two screening sites were added, closer to low-income neighbourhoods which had very low participation in the first study. This paper aims to analyse the geographic and socio-demographic disparities in uptake in the second trial and compare the results with the first trial. Methods Inhabitants of the Stockholm region born in 1940 and 1941 were randomised 1:1 to be invited to screening or serve as controls. Medical history, blood samples and single-lead-ECG were collected. Invitee's residential parish was used for geo-mapping analysis of the geographical disparities in participation, using hierarchical Bayes methods. Individual data for participants and non-participants were obtained for the socioeconomic variables: educational level, disposable income, immigrant and marital status. Results Higher participation was observed in those with higher education, high income, among non-immigrants and married individuals. Participation between the first and second studies improved significantly, where additional screening sites were introduced. These improvements were generally significant, in each population group according to socio-demographic characteristics. Conclusion Decentralisation of screening sites in an atrial fibrillation screening program yielded a significantly positive impact on screening uptake. Adding local screening sites in areas with low uptake had beneficial impact on participation across a wide spectrum of socio-demographic groups. Decentralised screening substantially increased the screening uptake in deprived areas.
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| 9. |
- Jacobsson, J. A., et al.
(författare)
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Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.
- 2008
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:11, s. 1730-1735
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.
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| 10. |
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