High pre-transplant serum nitrate levels predict risk of acute steroid-refractory graft-versus-host disease in the absence of statin therapy

Steroid-refractory graft-versus-host disease is a life-threatening complication after allogeneic stem cell transplantation. Evidence is accumulating that steroid-refractory graft-versus-host disease is associated with endothelial distress. Endothelial cell homeostasis is regulated by nitric oxide, and serum nitrates are derived from nitric oxide synthase activity or dietary sources. In this retrospective study based on 417 patients allografted at our institution we investigated whether quantification of serum nitrates could predict steroid-refractory graft-versus-host disease. Elevated pre-transplant levels of serum nitrates (>26.5 μM) predicted steroid-refractory graft-versus-host disease (P=0.026) and non-relapse mortality (P=0.028), particularly in combination with high pre-transplant angiopoietin-2 levels (P=0.0007 and P=0.021, respectively). Multivariate analyses confirmed serum nitrates as independent predictors of steroid-refractory graft-versus-host disease and non-relapse mortality. Differences in serum nitrate levels did not correlate with serum levels of tumor necrosis factor or C-reactive protein or expression of inducible nitric oxide synthase in blood cells. Patients with high pre-transplant nitrate levels had significantly reduced rates of refractory graft-versus-host disease (P=0.031) when pravastatin was taken. In summary, patients at high risk of developing steroid-refractory graft-versus-host disease could be identified prior to transplantation by serum markers linked to endothelial cell function. Retrospectively, statin medication was associated with a reduced incidence of refractory graft-versus-host disease in this endothelial high-risk cohort.     

Epidemiology of injuries during the Wheelchair Basketball World Championships 2018: A prospective cohort study

Several international sports federations have implemented a standardized injury reporting system during their championships. However, very few studies have investigated athletes with disabilities during major championships apart from the Paralympic Games. Therefore, the aim of this study was to assess the rate and characteristics of injuries during the Wheelchair Basketball World Championships 2018 (WBWC). This prospective cohort study was conducted during the WBWC held in Hamburg, Germany, from August 16 to August 26, 2018. Physicians or physiotherapists of all 28 participating teams (total 336 players) were asked to report all newly incurred injuries (with location, diagnosis, cause, and estimated duration of absence) daily on a standardized injury report form. Prevalence and incidence rates were calculated. Medical staff of 11 teams (132 players) reported 100 injuries, equivalent to 75.8 per 100 players (95% CI: 60.9-90.7) or 68.9 per 1000 player-days (55.4-82.4). Eight time-loss injuries were reported (6.1 injuries per 100 players [95% CI: 1.9-10.3] or 5.5 injuries per 1000 player-days [1.7-9.3]). More injuries were incurred during matches (n = 68) than during training. Most injuries affected the neck/cervical spine (16%), thoracic spine/upper back (15%), and shoulder (14%). The most frequent diagnosis was muscle spasms (25%), the most frequent cause was overuse (52%). A high rate of non–time-loss injuries compared to Paralympic Games was reported. Future studies should focus on the etiology of muscle spasms and further identify injury mechanisms of traumatic and overuse injuries in wheelchair basketball players to develop adequate preventive measures.     

Inter-laboratory study on standardized MPS libraries: evaluation of performance,concordance, and sensitivity using mixtures and degraded DNA

International Journal of Legal Medicine - We present results from an inter-laboratory massively parallel sequencing (MPS) study in the framework of the SeqForSTRs project to evaluate forensically...     

Is normalized hindlimb length measurement in assessment of thyroid disruption in the amphibian metamorphosis assay relevant?

The amphibian metamorphosis assay represents an OECD Level 3 and EDSP Tier 1 ecotoxicity test assessing thyroid activity of chemicals in African clawed frog (Xenopus laevis). To evaluate the effectiveness of snout‐vent length (SVL) normalization of hindlimb length (HLL), correlation between the HLL and SVL or body weight was evaluated in the control groups of 10 individual studies from three laboratories. Two studies required separate analysis of the Nieuwkoop‐Faber (NF) stage ≤60 and >60 animals creating a total of 12 data sets. On study day 7, significant positive correlation between HLL and SVL or body weight was observed in eight and seven of the 10 data sets, respectively (r = 0.608‐0.843 and 0.583‐0.876). On study day 21, significant positive correlation between HLL and SVL or body weight was found in three and four of the 12 data sets, respectively (r = 0.452, 0.480 and 0.553 and r = 0.621, 0.546, 0.564 and 0.378). Significant positive correlation between HLL and SVL was found in three of five studies, including ≤NF stage 60 data (r = 0.564, 0.546 and 0.621). In one of eight studies, including >NF stage 60 data, the positive correlation between HLL and body weight was determined (r = 0.378). Negative or no correlation between HLL and SVL or body weight was found in the other late stage data sets. Therefore, use of SVL‐normalized HLL to assess thyroid‐mediated effects in X. laevis tadpoles is not warranted. HL stage relative to body stage should be considered.     

Th17 cells in inflammation and autoimmunity

T helper 17 (Th17), a distinct subset of CD4⁺ T cells with IL-17 as their major cytokine, orchestrate the pathogenesis of inflammatory and autoimmune diseases. Dysregulated Th17 cells contribute to inflammatory and autoimmune diseases. Candidate biologics are in development for targeting IL-17, IL-17 receptors or IL-17 pathways. Several drugs that impact the IL-17 pathway are already in clinical trials for the treatment of autoimmune diseases. In this review we provide evidence for the role of Th17 cells in immune-mediated diseases. An understanding of the role of Th17 in these conditions will provide important insights and unravel novel targets for therapeutic intervention.     

Atmosphere-sensitive photoluminescence of CoxFe3−xO4 metal oxide nanoparticles

In this work the photoluminescence (PL) of Co_xFe_3−xO₄ spinel oxide nanoparticles under pulsed UV laser irradiation (λ_exc = 270 nm) is investigated for varying Co/Fe ratios (x = 0.4_⋯2.5). A broad emission in the green spectral range is observed, exhibiting two maxima at around 506 nm, which is dominant for Fe-rich nanoparticles (x = 0.4, 0.9), and at around 530 nm, that is more pronounced for Co-rich nanoparticles (x > 1.6). As examinations in different atmospheres show that the observed emission reacts sensitively to the presence of water, it is proposed that the emission is mainly caused by OH groups with terminal or bridging metal–O bonds on the Co_xFe_3−xO₄ surface. Raman spectroscopy supports that the emission maximum at 506 nm corresponds to terminal OH groups bound to metal cations on tetrahedral sites (i.e., Fe³⁺), while the maximum around 530 nm corresponds to terminal OH groups bound to metal cations on octahedral sites (i.e., Co³⁺). Photoinduced dehydroxylation shows that OH groups can be removed on Fe-rich nanoparticles more easily, leading to a conversion process and the formation of new OH groups with different bonds to the surface. As such behavior is not observed for Co_xFe_3−xO₄ with x > 1.6, we conclude that the OH groups are more stable against dehydroxylation on Co-rich nanoparticles. The higher OH stability is expected to lead to a higher catalytic activity of Co-rich cobalt ferrites in the electrochemical generation of oxygen.

Co_xFe_3−xO₄ (0.4 < x < 2.5) nanoparticles show a broad green emission induced by surface OH-groups with a lower stability regarding UV-photoinduced dehydroxylation on Fe-rich (x ≤ 1.6) nanoparticles.