Background
The increasing production of nanoplastics and the fragmentation of microplastics into smaller particles suggest a plausible yet unclear hazard in the natural environment, such as soil. We ...investigated the short-term effects (28 days) of polystyrene nanoparticles (PS-NPs) on the activity and biomass of soil microbiota, and the functional diversity of soil enzymes at environmental relevant low levels in an incubation experiment.
Results
Our results showed a significant decrease in microbial biomass in treatments of 100 and 1000 ng PS-NP g
−1
DM throughout the incubation period. Dehydrogenase activity and activities of enzymes involved in
N
-(leucine-aminopeptidase),
P
-(alkaline-phosphatase), and C-(β-glucosidase and cellobiohydrolase) cycles in the soil were significantly reduced at day 28 suggesting a broad and detrimental impact of PS-NPs on soil microbiota and enzymes. Leucine-aminopeptidase and alkaline-phosphatase activities tended to decrease consistently, while β-glucosidase and cellobiohydrolase activities increased at high concentrations (e.g., PS-NP-1000) in the beginning of the incubation period, e.g., at day 1. On the other hand, basal respiration and metabolic quotient increased with increasing PS-NP application rate throughout the incubation period possibly due to increased cell death that caused substrate-induced respiration (cryptic growth).
Conclusions
We herewith demonstrated for the first time the potential antimicrobial activity of PS-NPs in soil, and this may serve as an important resource in environmental risk assessment of PS-NPs in the soil environment.
Background There is scarce data about the long-term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy-proven ...viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10-year follow-up in patients with biopsy-proven myocarditis. Methods and Results Two-hundred three consecutive patients with biopsy-proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow-up. The median follow-up was 10.1 years. End points were all-cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long-term mortality in patients with biopsy-proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio HR, 2.40; 95% CI, 1.30-4.43), escalating to a HR of 3.00 (95% CI, 1.41-6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95-112.00) for SCD; all
≤0.009. Specifically, midwall, (antero-) septal LGE, and extent of LGE were highly associated with death, all
<0.001. Septal LGE was the best independent predictor for SCD (HR, 4.59; 95% CI, 1.38-15.24;
=0.01). Conclusions In patients with biopsy-proven viral myocarditis, the presence of midwall LGE in the (antero-) septal segments is associated with a higher rate of mortality (including SCD) compared with absent LGE or other LGE patterns, underlining the prognostic benefit of a distinct LGE analysis in these patients.
Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors ...(ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown.
The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort.
A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell–inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02–3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort.
High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.
•Accurate estimation of tumour mutational burden (TMB) by gene panel sequencing.•High TMB identifies patients with poor overall survival after chemoradiation.•TP53 mutations and unfavourable immune expression patterns associated with high TMB.
This study aimed to follow the impact of human papillomavirus (HPV) catch-up and vaccination on the very high cervical HPV-prevalence in women at a youth clinic in central Stockholm during the period ...2008-2018.
2008-2010, cervical HPV-prevalence (69.5%) and HPV16 prevalence (34.7%) were high in non-vaccinated women at a youth clinic in Stockholm. 2013-2015, after the introduction of the quadrivalent-Gardasil® HPV-vaccine, HPV16 and HPV6 prevalence had decreased. Here, cervical HPV-prevalence was investigated 10 years after primary sampling.
2017-2018, 178 cervical swabs, from women aged 15-23 years old, were tested for 27 HPV types by a bead-based multiplex method. HPV-prevalence data were then related to vaccination status and age and compared to HPV-prevalence in 615 samples from 2008 to 2010 and 338 samples from 2013 to 2015 from the same clinic, and to HPV types in 143 cervical cancer cases during 2003-2008 in Stockholm.
The proportion of vaccinated women increased from 10.7% (2008-2010) to 82.1% (2017-2018). The prevalence of all 27 HPVs, all high-risk HPVs (HR-HPVs) and the combined presence of the quadrivalent-Gardasil® types HPV16, 18, 6, and 11, was lower in vaccinated compared to unvaccinated women (67.4 vs. 93.3%,
= 0.0031, 60.1 vs. 86.7%,
= 0.0057 and 5.8 vs. 26.7%,
= 0.002, respectively). Furthermore, HPV16 prevalence in non-vaccinated women 2017-2018 was lower than that in 2008-2010 (16.7 and 34.7%, respectively,
= 0.0471) and similar trends were observed for HPV18 and 11. In both vaccinated and non-vaccinated women, the most common non-quadrivalent-Gardasil® vaccine HR-HPV types were HPV39, 51, 52, 56, and 59. Together they accounted for around 9.8% of cervical cancer cases in Stockholm during 2003-2008, and their prevalence tended to have increased during 2017-2018 compared to 2008-2010.
Quadrivalent-Gardasil® vaccination has decreased HPV-vaccine type prevalence significantly. However, non-vaccine HR-HPV types remain high in potentially high-risk women at a youth clinic in Stockholm.
Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at ...single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population ...structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer's disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD.
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Fracture treatment in children needs new implant materials to overcome disadvantages associated with removal surgery. Magnesium-based implants constitute a biocompatible and ...bioresorbable alternative. In adults and especially in children, implant safety needs to be evaluated. In children the bone turnover rate is higher and implant material might influence growth capacity, and the long-term effect of accumulated particles or ions is more critical due to the host’s prolonged post-surgery lifespan. In this study we aimed to investigate the degradation behavior of ZX00 (Mg-0.45Zn-0.45Ca; in wt.%) in a small and a large animal model to find out whether there is a difference between the two models (i) in degradation rate and (ii) in bone formation and in-growth. Our results 6, 12 and 24 weeks after ZX00 implantation showed no negative effects on bone formation and in-growth, and no adverse effects such as fibrotic or sclerotic encapsulation. The degradation rate did not significantly differ between the two growing-animal models, and both showed slow and homogeneous degradation performance. Our conclusion is that small animal models may be sufficient to investigate degradation rates and provide preliminary evidence on bone formation and in-growth of implant materials in a growing-animal model.
The safety of implant material is of the utmost importance, especially in children, who have enhanced bone turnover, more growth capacity and longer postoperative lifespans. Magnesium (Mg)-based implants have long been of great interest in pediatric orthopedic and trauma surgery, due to their good biocompatibility, biodegradability and biomechanics. In the study documented in this manuscript we investigated Mg–Zn–Ca implant material without rare-earth elements, and compared its outcome in a small and a large growing-animal model. In both models we observed bone formation and in-growth which featured no adverse effects such as fibrotic or sclerotic encapsulation, and slow homogeneous degradation performance of the Mg-based implant material.
Streams of high speed dust particles originate from Jupiter's moon Io. After release from Io, the particles collect electric charges in the Io plasma torus, gain energy from the co‐rotating electric ...field of Jupiter's magnetosphere, and leave the Jovian system into interplanetary space with escape speeds over 200 km s−1. The Galileo spacecraft has continuously monitored the dust streams during 34 revolutions about Jupiter between 1996 and 2002. The observed dust fluxes exhibit large orbit‐to‐orbit variability due to systematic and stochastic changes. After removal of the systematic variations, the total dust emission rate of Io has been calculated. It varies between 10−3 and 10 kg s−1, and is typically in the range of 0.1 to 1 kg s−1. We compare the dust emission rate with other markers of volcanic activity on Io like large‐area surface changes caused by volcanic deposits and sightings of volcanic plumes.
The Ulysses spacecraft has been orbiting the Sun on a highly inclined ellipse (
i
=
79
∘
, perihelion distance 1.3
AU, aphelion distance 5.4
AU) since it encountered Jupiter in February 1992. Since ...then it has made almost three revolutions about the Sun. Here we report on the final three years of data taken by the on-board dust detector. During this time, the dust detector recorded 609 dust impacts of particles with masses
10
−
16
g
⩽
m
⩽
10
−
7
g
, bringing the mission total to 6719 dust data sets. The impact rate varied from a low value of 0.3 per day at high ecliptic latitudes to 1.5 per day in the inner solar system. The impact direction of the majority of impacts between 2005 and 2007 is compatible with particles of interstellar origin; the rest are most likely interplanetary particles. We compare the interstellar dust measurements from 2005/2006 with the data obtained during earlier periods (1993/1994) and (1999/2000) when Ulysses was traversing the same spatial region at southern ecliptic latitudes but the solar cycle was at a different phase. During these three intervals the impact rate of interstellar grains varied by more than a factor of two. Furthermore, in the two earlier periods the grain impact direction was in agreement with the flow direction of the interstellar helium while in 2005/2006 we observed a shift in the approach direction of the grains by approximately
30
∘
away from the ecliptic plane. The reason for this shift remains unclear but may be connected with the configuration of the interplanetary magnetic field during solar maximum. We also find that the dust measurements are in agreement with the interplanetary flux model of
Staubach et al. (1997) which was developed to fit a 5-year span of Ulysses data.
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