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| 2. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 3. |
- Gällentoft, Lina, et al.
(författare)
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Impact of degradable nanowires on long-term brain tissue responses
- 2016
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Ingår i: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses. Results: The tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described. Conclusion: The present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.
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| 4. |
- Gällentoft, Lina, et al.
(författare)
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Size-dependent long-term tissue response to biostable nanowires in the brain.
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 42, s. 172-183
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Tidskriftsartikel (refereegranskat)abstract
- Nanostructured neural interfaces, comprising nanotubes or nanowires, have the potential to overcome the present hurdles of achieving stable communication with neuronal networks for long periods of time. This would have a strong impact on brain research. However, little information is available on the brain response to implanted high-aspect-ratio nanoparticles, which share morphological similarities with asbestos fibres. Here, we investigated the glial response and neuronal loss in the rat brain after implantation of biostable and structurally controlled nanowires of different lengths for a period up to one year post-surgery. Our results show that, as for lung and abdominal tissue, the brain is subject to a sustained, local inflammation when biostable and high-aspect-ratio nanoparticles of 5 μm or longer are present in the brain tissue. In addition, a significant loss of neurons was observed adjacent to the 10 μm nanowires after one year. Notably, the inflammatory response was restricted to a narrow zone around the nanowires and did not escalate between 12 weeks and one year. Furthermore, 2 μm nanowires did not cause significant inflammatory response nor significant loss of neurons nearby. The present results provide key information for the design of future neural implants based on nanomaterials.
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| 5. |
- Hellström, Lina, 1975-, et al.
(författare)
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Errors in medication history at hospital admission: prevalence and predicting factors
- 2012
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Ingår i: BMC Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1472-6904. ; 12, s. Article ID: 9-
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Tidskriftsartikel (refereegranskat)abstract
- Background: An accurate medication list at hospital admission is essential for the evaluation and further treatment of patients. The objective of this study was to describe the frequency, type and predictors of errors in medication history, and to evaluate the extent to which standard care corrects these errors.Methods:A descriptive study was carried out in two medical wards in a Swedish hospital using Lund Integrated Medicines Management (LIMM)-based medication reconciliation. A clinical pharmacist identified each patient's most accurate pre-admission medication list by conducting a medication reconciliation process shortly after admission. This list was then compared with the patient's medication list in the hospital medical records. Addition or withdrawal of a drug or changes to the dose or dosage form in the hospital medication list were considered medication discrepancies. Medication discrepancies for which no clinical reason could be identified (unintentional changes) were considered medication history errors.Results: The final study population comprised 670 of 818 eligible patients. At least one medication history error was identified by pharmacists conducting medication reconciliations for 313 of these patients (47%; 95% CI 43-51%). The most common medication error was an omitted drug, followed by a wrong dose. Multivariate logistic regression analysis showed that a higher number of drugs at admission (odds ratio [OR] per 1 drug increase = 1.10; 95% CI 1.06 - 1.14; p<0.0001) and the patient living in their own home without any care services (OR1.58; 95% CI 1.02 - 2.45; p = 0.042) were predictors for medication history errors at admission. The results further indicated that standard care by non-pharmacist ward staff had partly corrected the errors in affected patients by four days after admission, but a considerable proportion of the errors made in the initial medication history at admission remained undetected by standard care (OR for medication errors detected by pharmacists' medication reconciliation carried out on days 4 - 11 compared to days 0 - 1 = 0.52; 95% CI 0.30 - 0.91; p = 0.021).Conclusions: Clinical pharmacists conducting LIMM-based medication reconciliations have a high potential for correcting errors in medication history for all patients. In an older Swedish population, those prescribed many drugs seem to benefit most from admission medication reconciliation.
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| 6. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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The sex-stratified genetic architecture of ankylosing spondylitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sexual dimorphism is an emerging feature of ankylosing spondylitis (AS), a chronic rheumatic condition affecting upto three times more men than women. Using 691 individuals from a Swedish case-control cohort, we revealed thatsex biases are also a hallmark of AS genetic predisposition, and that this multifactorial disease is in part driven byboth rare and common variants. We identified SNPs via the targeted re-sequencing of 7 270 coding and non-codingloci, and assessed novel patterns of association with both single marker and aggregate loci SKAT tests. The malespecific RUNX3 locus (including rs7414934, OR=2.58, p=1.7x10-5) and female specific MICB SKAT locus (27variants, p=1.2x10-6; rs3828903, OR=4.62, p=6.2x10-13) exceeded discovery thresholds. Multiple risk variants fromeach locus were shown to be functionally active in immune (Jurkat), skin (HaCat) and bone (SaOS-2) cell lines.Differential patterns of genetic predisposition may point to alternative disease mechanisms in male and femalepatients. Genetic and functional analyses demonstrated that risk alleles should not be considered in isolation and thatassociated variants would likely affect gene regulation across multiple tissues. This work illustrates the need toconsider the contribution of sex to the genetics of AS and the duality that individual loci may play in the key clinical outcomes of disease.
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| 7. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 8. |
- Ahlgren-Berg, Alexandra, et al.
(författare)
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A comparative analysis of the bifunctional Cox proteins of two heteroimmune P2-like phages with different host integration sites
- 2009
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 385:2, s. 303-12
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Tidskriftsartikel (refereegranskat)abstract
- The Cox protein of the coliphage P2 is multifunctional; it acts as a transcriptional repressor of the Pc promoter, as a transcriptional activator of the P(LL) promoter of satellite phage P4, and as a directionality factor for site-specific recombination. The Cox proteins constitute a unique group of directionality factors since they couple the developmental switch with the integration or excision of the phage genome. In this work, the DNA binding characteristics of the Cox protein of WPhi, a P2-related phage, are compared with those of P2 Cox. P2 Cox has been shown to recognize a 9 bp sequence, repeated at least 6 times in different targets. In contrast to P2 Cox, WPhi Cox binds with a strong affinity to the early control region that contains an imperfect direct repeat of 12 nucleotides. The removal of one of the repeats has drastic effects on the capacity of WPhi to bind to the Pe-Pc region. Again in contrast to P2 Cox, WPhi Cox has a lower affinity to attP compared to the Pe-Pc region, and a repeat of 9 bp can be found that has 5 bp in common with the repeat in the Pe-Pc region. WPhi Cox, however, is essential for excisive recombination in vitro. WPhi Cox, like P2 Cox, binds cooperatively with integrase to attP. Both Cox proteins induce a strong bend in their DNA targets upon binding.
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| 9. |
- Ahmad, Awais, et al.
(författare)
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Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes
- 2021
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell Publishing Inc.. - 0009-9104 .- 1365-2249. ; 203:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjogrens syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver-kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti-nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD-associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2 center dot 9%) and three pSS (2 center dot 6%) cases were diagnosed with AILD. Among SLE-cases without known AILD (n = 272), 26 (9 center dot 6%) had PBC-associated autoantibodies, 15 (5 center dot 5%) AIH-associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC-associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7 center dot 4%), while one fulfilled the diagnostic PBC-criteria. AMA-M2 detected by immunoblot was the most common PBC-associated autoantibody in SLE (20 of 272, 7 center dot 4%). The prevalence of SMA (4 center dot 4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH-criteria. The patient with combined AIH/PBC-serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8 center dot 1%) had PBC-associated, 12 (10 center dot 8%) AIH-associated autoantibodies and two overlapped. PBC-associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD-associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody-negative and -positive patients.
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| 10. |
- Al Musawi, Ahmed, et al.
(författare)
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Intervention for a correct medication list and medication use in older adults : a non-randomised feasibility study among inpatients and residents during care transitions
- 2024
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Ingår i: International Journal of Clinical Pharmacy. - : Springer. - 2210-7703 .- 2210-7711.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMedication discrepancies in care transitions and medication non-adherence are problematic. Few interventions consider the entire process, from the hospital to the patient's medication use at home.AimIn preparation for randomised controlled trials (RCTs), this study aimed (1) to investigate the feasibility of recruitment and retention of patients, and data collection to reduce medication discrepancies at discharge and improve medication adherence, and (2) to explore the outcomes of the interventions.MethodParticipants were recruited from a hospital and a residential area. Hospital patients participated in a pharmacist-led intervention to establish a correct medication list upon discharge and a follow-up interview two weeks post-discharge. All participants received a person-centred adherence intervention for three to six months. Discrepancies in the medication lists, the Beliefs about Medicines Questionnaire (BMQ-S), and the Medication Adherence Report Scale (MARS-5) were assessed.ResultsOf 87 asked to participate, 35 were included, and 12 completed the study. Identifying discrepancies, discussing discrepancies with physicians, and performing follow-up interviews were possible. Conducting the adherence intervention was also possible using individual health plans for medication use. Among the seven hospital patients, 24 discrepancies were found. Discharging physicians agreed that all discrepancies were errors, but only ten were corrected in the discharge information. Ten participants decreased their total BMQ-S concern scores, and seven increased their total MARS-5 scores.ConclusionBased on this study, conducting the two RCTs separately may increase the inclusion rate. Data collection was feasible. Both interventions were feasible in many aspects but need to be optimised in upcoming RCTs.
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