The complex and enormous diversity of microorganisms associated with plant roots is important for plant health and growth and is shaped by numerous factors. This study aimed to unravel the effects of ...the soil type on bacterial communities in the rhizosphere of field-grown lettuce. We used an experimental plot system with three different soil types that were stored at the same site for 10 years under the same agricultural management to reveal differences directly linked to the soil type and not influenced by other factors such as climate or cropping history. Bulk soil and rhizosphere samples were collected 3 and 7 weeks after planting. The analysis of 16S rRNA gene fragments amplified from total community DNA by denaturing gradient gel electrophoresis and pyrosequencing revealed soil type dependent differences in the bacterial community structure of the bulk soils and the corresponding rhizospheres. The rhizosphere effect differed depending on the soil type and the plant growth developmental stage. Despite the soil type dependent differences in the bacterial community composition several genera such as Sphingomonas, Rhizobium, Pseudomonas, and Variovorax were significantly increased in the rhizosphere of lettuce grown in all three soils. The number of rhizosphere responders was highest 3 weeks after planting. Interestingly, in the soil with the highest numbers of responders the highest shoot dry weights were observed. Heatmap analysis revealed that many dominant operational taxonomic units were shared among rhizosphere samples of lettuce grown in diluvial sand, alluvial loam, and loess loam and that only a subset was increased in relative abundance in the rhizosphere compared to the corresponding bulk soil. The findings of the study provide insights into the effect of soil types on the rhizosphere microbiome of lettuce.
Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of ...activating their residual vision.
We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology.
The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions.
rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way.
ClinicalTrials.gov NCT01280877.
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Background In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients ...with end-stage renal disease. Study Design Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design. Setting & Population Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis. Selection Criteria for Studies Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk. Intervention In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B12 and B6 , were used. Outcomes In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality. Results In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 μmol/L; 95% confidence interval CI, −2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-μmol/L increase) and total mortality (hazard ratio HR, 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9). Limitations Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible. Conclusion Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.
Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital.
A ...single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls. VRE isolates of cases were typed by multi-locus sequence typing.
ST117 was identified as the dominant VRE sequence type. Next to length of stay in hospital or on an intensive care unit and previous dialysis the case-control study revealed previous antibiotic therapy as a risk factor for the in-hospital detection of VRE. The antibiotics piperacillin/tazobactam, meropenem, and vancomycin were associated with the highest risks. After taking into account length of stay in hospital as possible confounder other potential contact-related risk factors such as previous sonography, radiology, central venous catheter, and endoscopy were not significant.
Previous dialysis and previous antibiotic therapy were identified as independent risk factors for the presence of VRE in surgical inpatients.
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4D flow MRI enables quantitative assessment of helical flow. Current methods are susceptible to noise. To evaluate helical flow patterns in healthy volunteers and patients with bicuspid aortic valves ...(BAV) at 1.5 T and 3 T using pressure-based helix-extraction in 4D flow MRI. Two intraindividual 4D flow MRI examinations were performed at 1.5 T and 3 T in ten healthy volunteers (5 females, 32 ± 3 years) and 2 patients with BAV using different acceleration techniques (kt-GRAPPA and centra). Several new quantitative parameters for the evaluation of volumes ml, lengths mm as well as temporal parameters ms of helical flow were introduced and analyzed using the software tool Bloodline. We found good correlations between measurements in volunteers at 1.5 T and 3 T regarding helical flow volumes (R = 0.98) and temporal existence (R = 0.99) of helices in the ascending aorta. Furthermore, we found significantly larger (11.7 vs. 77.6 ml) and longer lasting (317 vs. 769 ms) helices in patients with BAV than in volunteers. The assessed parameters do not depend on the magnetic field strength used for the acquisition. The technique of pressure-based extraction of 4D flow MRI pattern is suitable for differentiation of normal and pathological flow.
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In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic ...analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 62%), 1 (9/37 24%), 18 (7/37 19%), and 14 (5/37 14%). Tumors with
NF2
alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent
NF2
alterations, while other typical alterations found in adult non-
NF2
tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
High-grade B cell lymphomas with concomitant
and
and/or
rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like chemoimmunotherapy protocol. Whether this can be ...improved using intensified regimens is still under debate. However, due to the rarity of HGBCL-DH/TH there are no prospective, randomized controlled trials (RCT) available. Thus, with this systematic review and meta-analysis we attempted to compare survival in HGBCL-DH/TH patients receiving intensified vs. R-CHOP(-like) regimens.
The PubMed and Web of Science databases were searched for original studies reporting on first-line treatment in HGBCL-DH/TH patients from 08/2014 until 04/2022. Studies with only localized stage disease, ≤10 patients, single-arm, non-full peer-reviewed publications, and preclinical studies were excluded. The quality of literature and the risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Random-effect models were used to compare R-CHOP-(like) and intensified regimens regarding 2-year overall survival (2y-OS) and 2-year progression-free survival (2y-PFS).
Altogether, 11 retrospective studies, but no RCT, with 891 patients were included. Only four studies were of good quality based on aforementioned criteria. Intensified treatment could improve 2y-OS (hazard ratio HR=0.78 95% confidence interval CI 0.63-0.96; p=0.02) as well as 2y-PFS (HR=0.66 95% CI 0.44-0.99; p=0.045).
This meta-analysis indicates that intensified regimens could possibly improve 2y-OS and 2y-PFS in HGBCL-DH/TH patients. However, the significance of these results is mainly limited by data quality, data robustness, and its retrospective nature. There is still a need for innovative controlled clinical trials in this difficult to treat patient population.
https://www.crd.york.ac.uk/prospero, identifier CRD42022313234.
Every sixth child suffers from hypertrophy of the adenoid, a secondary lymphoid organ, at least once in childhood. Little is known about the impact of pathogen-provocation vs. developmental impact on ...T-cell responses after 1 year of age. Therefore, developmental and infection-driven influences on the formation of T-cell-compartments and -multifunctionality in adenoids were analyzed taking into account patient's history of age and inflammatory processes. Here, we show that in adenoids of 102 infants and children similar frequencies of naïve, effector, and memory T-cells were accumulated, whereby history of suffering from subsequent infection symptoms resulted in lower frequencies of CD4
and CD8
T-cells co-expressing several cytokines. While patients suffering from sole nasal obstruction had balanced Th1- and Th17-compartments, Th1 dominated in patients with concomitant upper airway infections. In addition, analysis of cytokine co-expressing CD4
and CD8
T-cells showed that children at the age of three or older differed significantly from those being 1- or 2-years old, implicating a developmental switch in T-cell differentiation at that age. Yet, dissecting age and infectious history of the patients revealed that while CD8
T-cell differentiation seems to be triggered by development, CD4
T-cell functionality is partly impaired by infections. However, this functionality recovers by the age of 3 years. Thus, 3 years of age seems to be a critical period in an infant's life to develop robust T-cell compartments of higher quality. These findings identify important areas for future research and distinguish an age period in early childhood when to consider adjusting the choice of treatment of infections.
Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to ...radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).
Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data.
Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up.
The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1-8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI.
EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304.
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ABSTRACT
Introduction: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS). Methods: ...In 37 patients, ulnar and median nerve cross‐sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow‐up was 14.5 months. Linear mixed‐effects models were conducted to analyze time effects on CSA. Results: Ulnar nerve CSA declined significantly at a monthly rate of –0.04 mm2 (forearm) and –0.05 mm2 (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA. Conclusions: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391–397, 2016
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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