Pretransplant risk assessment of graft failure is important for donor selection and choice of immunosuppressive treatment. We examined the relation between kidney graft failure and presence of IgG ...donor specific HLA antibodies (DSA) or C1q‐fixing DSA, detected by single antigen bead array (SAB) in pretransplant sera from 837 transplantations. IgG‐DSA were found in 290 (35%) sera, whereas only 30 (4%) sera had C1q‐fixing DSA. Patients with both class‐I plus ‐II DSA had a 10 yr graft survival of 30% versus 72% in patients without HLA antibodies (p < 0.001). No significant difference was observed in graft survival between patients with or without C1q‐fixing DSA. Direct comparison of both assays showed that high mean fluorescence intensity values on the pan‐IgG SAB assay are generally related to C1q‐fixation. We conclude that the presence of class‐I plus ‐II IgG DSA as detected by SAB in pretransplant sera of crossmatch negative kidney recipients is indicative for an increased risk for graft failure, whereas the clinical significance of C1q‐fixing IgG‐DSA could not be assessed due to their low prevalence.
In a retrospective analysis using pretransplant sera from 837 kidney transplantations, this study compares the value of C1q‐fixing versus pan‐IgG donor‐specific HLA antibodies in risk assessment for kidney graft failure.
Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into ...multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study.
In total, 106 multimeric complexes were identified; in more than half of these at least one SEP protein was present. Besides the known complexes involved in determining floral organ identity, various complexes consisting of combinations of proteins known to play a role in floral organ identity specification, and flowering time determination were discovered. The capacity to form this latter type of complex suggests that homeotic factors play essential roles in down-regulation of the MADS box genes involved in floral timing in the flower via negative auto-regulatory loops. Furthermore, various novel complexes were identified that may be important for the direct regulation of the floral transition process. A subsequent detailed analysis of the APETALA3, PISTILLATA, and SEP3 proteins in living plant cells suggests the formation of a multimeric complex in vivo.
Overall, these results provide strong indications that higher-order complex formation is a general and essential molecular mechanism for plant MADS box protein functioning and attribute a pivotal role to the SEP3 'glue' protein in mediating multimerization.
Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic ...low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients.
Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria.
307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease.
Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Essentials
The association between chronic kidney disease and bleeding is unknown.
We followed 10 347 subjects at high cardiovascular risk for bleeding events.
Chronic kidney disease was associated ...with a 1.5‐fold increased bleeding risk.
Especially albuminuria rather than decreased kidney function was associated with bleeding events.
Summary
Background
There are indications that patients with chronic kidney disease have an increased bleeding risk.
Objectives
To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk.
Methods
We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease SMART cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses.
Results
The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person‐years and that for subjects without chronic kidney disease was 3.5 per 1000 person‐years. Patients with chronic kidney disease (n = 2443) had a 1.5‐fold (95% CI 1.2–1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of < 45 mL min−1 1.73 m–2 with albuminuria had a 3.5‐fold (95% CI 2.3–5.3) increased bleeding risk, whereas an eGFR of < 45 mL min−1 1.73 m–2 without albuminuria was not associated with an increased bleeding risk (HR 1.3, 95% CI 0.7–2.5).
Conclusion
Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria.
Background Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and ...neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. Methods This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). Discussion The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. Trial registration WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021). Keywords: Nutrition, Preterm infant, Docosahexaenoic acid, Brain development, MRI, White matter integrity, Neurodevelopment, Language
For the first time an excess of photons above an energy threshold of 730 GeV from the giant radio galaxy M 87 has been measured at a significance level above 4 σ. The data have been taken during the ...years 1998 and 1999 with the HEGRA stereoscopic system of 5 imaging atmospheric Cherenkov telescopes. The excess of $107.4\,\pm\,26.8$ events above 730 GeV corresponds to an integral flux of 3.3% of the Crab flux or $N_\gamma(E > 730\,\mbox{GeV}) = (0.96 \pm 0.23) \times 10^{-12}$ phot cm-2 s-1. M 87 is located at the center of the Virgo cluster of galaxies at a relatively small redshift of $z = 0.00436$ and is a promising candidate among the class of giant radio galaxies for the emission of TeV γ-radiation. The detection of TeV γ-rays from M 87 – if confirmed – would establish a new class of extragalactic source in this energy regime since all other AGN detected to date at TeV energies are BL Lac type objects.
The unidentified TeV source in Cygnus is now confirmed by follow-up observations from 2002 with the HEGRA stereoscopic system of Cherenkov Telescopes. Using all data (1999 to 2002) we confirm this ...new source as steady in flux over the four years of data taking, extended with radius 6.2′ (±$1.2^\prime_{\rm stat}$ ± $0.9^\prime_{\rm sys}$) and exhibiting a hard spectrum with photon index -1.9. It is located in the direction of the dense OB stellar association, Cygnus OB2. Its integral flux above energies $E>1$ TeV amounts to ~5% of the Crab assuming a Gaussian profile for the intrinsic source morphology. There is no obvious counterpart at radio, optical nor X-ray energies, leaving TeV J2032+4130 presently unidentified. Observational parameters of this source are updated here and some astrophysical discussion is provided. Also included are upper limits for a number of other interesting sources in the FoV, including the famous microquasar Cygnus X-3.
Summary
Antibodies recognizing denatured human leucocyte antigen (HLA) can co‐react with epitopes on intact HLA or recognize cryptic epitopes which are normally unaccessible to HLA antibodies. Their ...specificity cannot be distinguished by single antigen beads (SAB) alone, as they carry a mixture of intact and denatured HLA. In this study, we selected pretransplant sera containing donor‐specific HLA class I antibodies (DSA) according to regular SAB analysis from 156 kidney transplant recipients. These sera were analysed using a SAB preparation (iBeads) which is largely devoid of denatured HLA class I, and SAB coated with denatured HLA class I antigens. A total of 241 class I DSA were found by regular SAB analysis, of which 152 (63%) were also found by iBeads, whereas 28 (11%) were caused by reactivity with denatured DNA. Patients with DSA defined either by regular SAB or iBeads showed a significantly lower graft survival rate (P = 0·007) compared to those without HLA class I DSA, whereas reactivity to exclusively denatured HLA was not associated with decreased graft survival. In addition, DSA defined by reactivity to class I SAB or class I iBeads occurred more frequently in female patients and in patients with historic HLA sensitization, whereas reactivity to denatured HLA class I was not associated with any of these parameters. Our data suggest that pretransplant donor‐specific antibodies against denatured HLA are clinically irrelevant in patients already sensitized against intact HLA.
The Crab supernova remnant has been observed regularly with the stereoscopic system of five imaging air Cerenkov telescopes that was part of the High Energy Gamma Ray Astronomy (HEGRA) experiment. In ...total, close to 400 hr of useful data have been collected from 1997 to 2002. The differential energy spectrum of the combined data set can be approximated by a power law-type energy spectrum: d Phi /dE = Phi sub(0) (E/TeV) Gamma , Phi sub(0) = (2.83 plus or minus 0.04 sub(stat) plus or minus 0.6 sub(sys)) 10 super(-11) photons cm super(-2) s super(-1) TeV super(-1), and Gamma = -2.62 plus or minus 0.02 sub(stat) plus or minus 0.05 sub(sys). The spectrum extends up to energies of 80 TeV and is well matched by model calculations in the framework of inverse Compton scattering of various seed photons in the nebula, including for the first time a recently detected compact emission region at millimeter wavelengths. The observed indications for a gradual steepening of the energy spectrum in data is expected in the inverse Compton emission model. The average magnetic field in the emitting volume is determined to be 161.6 plus or minus 0.8 sub(stat) plus or minus 18 sub(sys) mu G. The presence of protons in the nebula is not required to explain the observed flux, and upper limits on the injected power of protons are calculated to be as low as 20% of the total spin-down luminosity for bulk Lorentz factors of the wind in the range of 10 super(4)-10 super(6). The position and size of the emission region have been studied over a wide range of energies. The position is shifted by 13" to the west of the pulsar, with a systematic uncertainty of 25". No significant shift in the position with energy is observed. The size of the emission region is constrained to be less than 2' at energies between 1 and 10 TeV. Above 30 TeV the size is constrained to be less than 3'. No indication of pulsed emission has been found, and upper limits in differential bins of energy have been calculated reaching typically 1%-3% of the unpulsed component.
Background
Data on chronic pain after kidney donation are sparse. The aim of this study was to assess the incidence of chronic pain after hand‐assisted laparoscopic nephrectomy.
Methods
Living kidney ...donors who donated between 2011 and 2017 at the University Medical Centre Groningen were included. All patients underwent hand‐assisted laparoscopic donor nephrectomy. Postdonation pain and movement disabilities were assessed using the Carolinas Comfort Scale (CCS) and a visual analogue scale (VAS). The prevalence, severity of pain and the need for analgesics were reported.
Results
Some 333 living kidney donors with a mean age of 56 years were included. At a median of 19 (i.q.r. 10–33) months after donation, 82 donors (24·6 per cent) had a CCS score above 0, of which 58 (71 per cent) had a CCS score of at least 2 and 57 (70 per cent) reported movement limitations. Some 110 donors (33·0 per cent) had a VAS score of more than 0. Complaints mainly occurred during bending over (12·3 per cent) and exercising (12·4 per cent). Thirty‐two donors (9·7 per cent) required analgesics during follow‐up between donation and the time of measurement, and six of 82 (7 per cent) reported chronic inguinal pain. In multivariable analysis, donor age (odds ratio (OR) 0·97, 95 per cent c.i. 0·95 to 0·99; P = 0·020) and length of hospital stay (OR 1·21, 1·01 to 1·51; P = 0·041) were independently associated with chronic pain.
Conclusion
One‐quarter of donors experienced chronic postdonation pain or discomfort, most of which was bothersome. Younger donors and those with a longer postoperative hospital stay had more symptoms.
Living donor nephrectomy is associated with chronic pain in 25 per cent of donors. Complaints occur during bending over and exercising. Younger donors and donors with a longer hospital stay had more complaints.
Significant in a quarter of patients
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