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- Sharma, S., et al.
(författare)
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Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades
- 2017
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 91:14
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII. 4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII. 4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of >= 160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII. 4 NoV. IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII. 4 NoV. The emergence of new pandemic GII. 4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.
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| 5. |
- Knip, Mikael, et al.
(författare)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 6. |
- Landegren, N, et al.
(författare)
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AIREing out autoimmunity
- 2015
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Ingår i: SCIENCE TRANSLATIONAL MEDICINE. - 1946-6234. ; 7:292
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Bybrant, M. C., et al.
(författare)
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Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p=.00001) and those with DQX/X (p.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p=.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
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- Hallberg, R. T., et al.
(författare)
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Hydrogen-assisted spark discharge generated metal nanoparticles to prevent oxide formation
- 2018
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 52:3, s. 347-358
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Tidskriftsartikel (refereegranskat)abstract
- There exists a demand for production of metal nanoparticles for today's emerging nanotechnology. Aerosol-generated metal nanoparticles can oxidize during particle formation due to impurities in the carrier gas. One method to produce unoxidized metal nanoparticles is to first generate metal oxides and then reduce them during sintering. Here, we propose to instead prevent oxidation by introducing the reducing agent already at particle formation. We show that by mixing 5% hydrogen into the nitrogen carrier gas, we can generate single crystalline metal nanoparticles by spark discharge from gold, cobalt, bismuth, and tin electrodes. The non-noble nanoparticles exhibit signs of surface oxidation likely formed post-deposition when exposed to air. Nanoparticles generated without hydrogen are found to be primarily polycrystalline and oxidized. To demonstrate the advantages of supplying the reducing agent at generation, we compare to nanoparticles that are generated in nitrogen and sintered in a hydrogen mixture. For bismuth and tin, the crystal quality of the particles after sintering is considerably higher when hydrogen is introduced at particle generation compared to at sintering, whereas for cobalt it is equally effective to only add hydrogen at sintering. We propose that hydrogen present at particle generation prevents the formation of oxide primary particles, thus improving the ability to sinter the nanoparticles to compact and single crystals of metal. This method is general and can be applied to other aerosol generation systems, to improve the generation of size-controlled nanoparticles of non-noble metals with a suitable reducing agent.
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| 9. |
- Kohut, A., et al.
(författare)
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From plasma to nanoparticles : Optical and particle emission of a spark discharge generator
- 2017
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Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 28:47
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Tidskriftsartikel (refereegranskat)abstract
- The increased demand for high purity nanoparticles (NPs) of defined geometry necessitates the continuous development of generation routes. One of the most promising physical techniques for producing metal, semiconductor or alloy NPs in the gas phase is spark discharge NP generation. The technique has a great potential for up-scaling without altering the particles. Despite the simplicity of the setup, the formation of NPs in a spark discharge takes place via complex multi-scale processes, which greatly hinders the investigation via conventional NP measurement techniques. In the present work, time-resolved optical emission spectroscopy (OES) was used to provide information on the species present in the spark from as early as approximately 100 ns after the initiation of the discharge. We demonstrate that operando emission spectroscopy can deliver valuable insights into NP formation. The emission spectra of the spark are used to identify, among others, the main stages of material erosion and to calculate the quenching rate of the generated metal vapour. We demonstrate that the alteration of key control parameters, that are typically used to optimize NP generation, clearly affect the emission spectra. We report for Cu and Au NPs that the intensity of spectral lines emitted by metal atoms levels off when spark energy is increased above an energy threshold, suggesting that the maximum concentration of metal vapour produced in the generator is limited. This explains the size variation of the generated NPs. We report a strong correlation between the optical and particle emission of the spark discharge generator, which demonstrate the suitability of OES as a valuable characterization tool that will allow for the more deliberate optimization of spark-based NP generation.
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| 10. |
- Liu, Po-Hong, et al.
(författare)
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Dietary Gluten Intake and Risk of Microscopic Colitis Among US Women without Celiac Disease : A Prospective Cohort Study
- 2019
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Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 114:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored.METHODS: We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI).RESULTS: We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17).CONCLUSION: Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.
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