104 research outputs found

    Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: 'Shrunken pore syndrome'.

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    The plasma levels of cystatin C, β2-microglobulin, beta-trace protein, retinol binding protein (RBP) and creatinine were determined in plasma samples from 111 randomly selected patients with eGFRcystatin C ≤ 60% of eGFRcreatinine and from 55 control patients with 0.9eGFRcreatinine ≤ eGFRcystatin C ≤ 1.1eGFRcreatinine (eGFRcystatin C ≈ eGFRcreatinine). The concentration ratios of cystatin C/creatinine, β2-microglobulin/creatinine, beta-trace protein/creatinine and RBP/creatinine were significantly higher in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine than in patients with eGFRcystatin C ≈ eGFRcreatinine. When the patients were divided into three groups with different estimated GFR intervals (≤ 40, 40-60 and ≥ 60 mL/min/1.73m(2)) the concentration ratios of cystatin C/creatinine, β2-microglobulin/creatinine, and beta-trace protein/creatinine were significantly higher in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine than in patients with eGFRcystatin C ≈ eGFRcreatinine for all GFR intervals. Similar results were obtained when the population without pregnant women was studied as well as the subpopulations of men or of non-pregnant women. Populations of pre-eclamptic women and pregnant women in the third trimester display similar results. Since the production of these four proteins with sizes similar to that of cystatin C is not co-regulated, the most likely explanation for the simultaneous increase of their creatinine-ratios in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine is that their elimination by glomerular filtration is decreased. We suggest that this is due to a reduction in pore diameter of the glomerular membrane and propose the designation 'Shrunken pore syndrome' for this pathophysiological state

    Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

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    Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p < 0.0001). Furthermore, in the group with 4th quartile LVAb, 55% were IAA positive (p = 0.01) and correlation was found between 4th quartile LVAb and IAA in children < 10 years of age (p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4th quartile LVAb correlated with IAA; and 3) there was a correlation between 4th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D

    Effect of Cooling Rate after Solution Treatment on Subsequent Phase Separation Evolution in Super Duplex Stainless Steel 25Cr-7Ni (wt.%)

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    The effect of cooling rate after solution treatment on the initial structure of super duplex stainless steel 25Cr-7Ni (wt.%), and the effect of the initial structure on phase separation (PS) evolution during subsequent aging were investigated. The nanostructure in the bulk of the steel was studied using small-angle neutron scattering (SANS). Ex situ SANS experiments showed that the rate of PS differs during aging, due to the different initial structures imposed by the difference in cooling rate after solution treatment. In situ SANS experiments revealed that the PS is already pronounced after aging at 475 ◦C for 180 min and that a slower cooling rate after solution treatment will lead to more significant PS. Hence, PS depends on the plate thickness, imposing different cooling rates in the production of duplex stainless steels

    Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome

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    Objectives Clinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.publishedVersio

    BACCHUS Analysis of Weak Lines in APOGEE Spectra (BAWLAS)

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    Elements with weak and blended spectral features in stellar spectra are challenging to measure and require specialized analysis methods to precisely measure their chemical abundances. In this work, we have created a catalog of approximately 120,000 giants with high signal-to-noise APOGEE DR17 spectra, for which we explore weak and blended species to measure Na, P, S, V, Cu, Ce, and Nd abundances and 12^{12}C/13^{13}C isotopic ratios. We employ an updated version of the BACCHUS (Brussels Automatic Code for Characterizing High accUracy Spectra) code to derive these abundances using the stellar parameters measured by APOGEE's DR17 ASPCAP pipeline, quality flagging to identify suspect spectral lines, and a prescription for upper limits. Combined these allow us to provide our BACCHUS Analysis of Weak Lines in APOGEE Spectra (BAWLAS) catalog of precise chemical abundances for these weak and blended species that agrees well with literature and improves upon APOGEE abundances for these elements, some of which are unable to be measured with APOGEE's current, grid-based approach without computationally expensive expansions. This new catalog can be used alongside APOGEE and provide measurements for many scientific applications ranging from nuclear physics to Galactic chemical evolution and Milky Way population studies. To illustrate this we show some examples of uses for this catalog, such as, showing that we observe stars with enhanced s-process abundances or that we can use the our 12^{12}C/13^{13}C ratios to explore extra mixing along the red giant branch.Comment: 49 Pages, 30 figures, 7 Tables. Accepted for publishing in The Astrophysical Journal Supplement Series. The BAWLAS chemical abundance catalog to be made publicly available as an SDSS DR17 value-added catalog: https://www.sdss.org/dr17/data_access/value-added-catalogs

    Maternal Enterovirus Infection during Pregnancy as a Risk Factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 Years of Age

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    Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22–17.6), as compared to boys of IgM-negative mothers (P < .025). These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood
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