Stress and Multiple Sclerosis - Systematic review and meta-analysis of the association with disease onset, relapse risk and disability progression.

OBJECTIVE: This systematic review and meta-analysis address the evidence on the association of psychological stressors with onset of multiple sclerosis, inflammatory disease activity (relapses or new disease activity on magnetic resonance imaging, MRI) and disability progression. METHODS: PubMed was searched from 1946 to 15 July 2022. Studies and certain stressors were selected when they assessed stressors independent from stress elicited by the disease process itself. Risk of bias was assessed by the CASP Case Control Study Checklist and the CASP Cohort Study Checklist. Normal-Normal Hierarchical Model (NNHM) for random-effects meta-analysis was used in the Bayesian framework. RESULTS: 30 studies reporting data from 26 cohorts reporting on 24.781 cases could be identified. Ten studies addressed stressors and MS disease onset showing a weak to modest effect of psychological stressors. A meta-analysis of three studies investigating diagnosed stress disorders and MS risk showed a 1.87-fold (CI 1.061 to 3.429) increased MS risk. Stress and MS relapse risk were addressed in 19 heterogeneous studies. Meta-analyses from two independent cohorts investigating the same military threat of a population showed a threefold increased risk for relapses in association with war (relapse rate: 3.0, CI 1.56 to 5.81). In addition, two studies confirmed an association of stressful life events and MRI activity. Three studies of stressors and disease progression were included indicating some effect on disease progression. CONCLUSIONS: Taken together studies indicate a minor to modest impact of psychological stressors on disease onset, inflammatory activity and progression of MS. Possible case-selection bias and lack of confounder analysis were present in many studies.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Modeling the environmental fate of bracken toxin ptaquiloside: Production, release and transport in the rhizosphere.

Plants produce a diverse array of toxic compounds which may be released by precipitation, explaining their wide occurrence in surrounding soil and water. This study presents the first mechanistic model for describing the generation and environmental fate of a natural toxin, i.e. ptaquiloside (PTA), a carcinogenic phytotoxin produced by bracken fern (Pteridium aquilinum L. Kuhn). The newly adapted DAISY model was calibrated based on two-year monitoring performed in the period 2018-2019 in a Danish bracken population located in a forest glade. Several functions related to the fate of PTA were calibrated, covering processes from toxin generation in the canopy, wash off by precipitation and degradation in the soil. Model results show a good description of observed bracken biomass and PTA contents, supporting the assumption that toxin production can be explained by the production of new biomass. Model results show that only 4.4 % of the PTA produced in bracken is washed off by precipitation, from both canopy and litter. Model simulations showed that PTA degrades rapidly once in the soil, especially during summer due to the high soil temperatures. Leaching takes place in form of pulses directly connected to precipitation events, with maximum simulated concentrations up to 4.39 µg L-1 at 50 cm depth. Macropore transport is mainly responsible for the events with the highest PTA concentrations, contributing to 72 % of the total mass of PTA leached. Based on the results, we identify areas with high density of bracken, high precipitation during the summer and soils characterized by fast transport, as the most vulnerable to surface and groundwater pollution by phytotoxins.

Nitrogen amended graphene catalyses fast reduction of vinyl chloride by nano zerovalent iron.

Vinyl chloride (VC) is a dominant carcinogenic residual in many aged chlorinated solvent plumes, and it remains a huge challenge to clean it up. Zerovalent iron (ZVI) is an effective reductant for many chlorinated compounds but shows low VC removal efficiency at field scale. Amendment of ZVI with a carbonaceous material may be used to both preconcentrate VC and facilitate redox reactions. In this study, nitrogen-doped graphene (NG) produced by a simple co-pyrolysis method using urea as nitrogen (N) source, was tested as a catalyst for VC reduction by nanoscale ZVI (nZVI). The extent of VC reduction to ethylene in the presence of 2 g/L of nZVI was less than 1% after 3 days, and barely improved with the addition of 4 g/L of graphene. In contrast, with amendment of nZVI with NG produced at pyrolysis temperature (PT) of 950 °C, the VC reduction extent increased more than 10-fold to 69%. The reactivity increased with NG PT increasing from 400 °C to an optimum at 950 °C, and it increased linearly with NG loadings. Interestingly, N dosage had little effect on reactivity if NG was produced at PT of 950 °C, while a positive correlation was observed for NG produced at PT of 600 °C. XPS and Raman analyses revealed that for NG produced at lower PT (<800 °C) mainly the content of pyridine-N-oxide (PNO) groups correlates with reactivity, while for NG produced at higher PT up to 950 °C, reactivity correlates mainly with N induced structural defects in graphene. The results of quenching and hydrogen yield experiments indicated that NG promote reduction of VC by storage of atomic hydrogen, thus increasing its availability for VC reduction, while likely also enabling electron transfer from nZVI to VC. Overall, these findings demonstrate effective chemical reduction of VC by a nZVI-NG composite, and they give insights into the effects of N doping on redox reactivity and hydrogen storage potential of carbonaceous materials.

Phosphorus doped cyanobacterial biochar catalyzes efficient persulfate oxidation of the antibiotic norfloxacin.

In this study, cyanobacterial biochars (CBs) enriched/doped with non-metallic elements were prepared by pyrolysis of biomass amended with different N, S, and P containing compounds. Their catalytic reactivity was tested for persulfate oxidation of the antibiotic norfloxacin (NOR). N and S doping failed to improve CB catalytic reactivity, while P doping increased reactivity 5 times compared with un-doped biochar. Biochars produced with organic phosphorus dopants showed the highest reactivity. Post-acid-washing improved catalytic reactivity. In particular, 950 ℃ acid-washed triphenyl-phosphate doped CB showed the largest degradation rate and reached 79% NOR mineralization in 2 h. Main attributes for P-doped CBs high reactivity were large specific surface areas (up to 655 m2/g), high adsorption, high C-P-O content, graphitic P and non-radical degradation pathway (electron transfer). This study demonstrates a new way to reuse waste biomass by producing efficient P-doped metal-free biochars and presents a basic framework for designing carbon-based catalysts for organic pollutant degradation.

Time course of optic nerve sheath dilation: In vitro response characteristics to controlled pressure elevations.

BACKGROUND: Optic nerve sheath (ONS) dilation indicates intracranial pressure elevation under clinical conditions but limited data exist with regard to the dynamics of sheath expansion. OBJECTIVE: To assess the time course of ONS widening and its stability under controlled pressure conditions in vitro. METHODS: Pre-defined pressure steps up to 65 mmHg were applied to the perineural space of ex-vivo human optic nerves (n = 16). Using ultrasound, the optic nerve sheath diameter (ONSD) was monitored over 500 s. Re-tests at low-pressure levels concluded each experimental series. RESULTS: In most cases, 50% of the total diameter-change were achieved within 50 s after pressure onset and 95% of the maximal diameter after 200 s. The diametric gains in each experiment were strongly correlated with the applied pressure levels (coefficient of variance 0,96) within preparations with variability of the transfer function across preparations. The time course of the dilation was found to follow an approximate natural logarithmic function (R2 = 0.93-0.99). The re-test condition revealed unchanged time course properties (5% significance level) despite starting regularly from a higher baseline-diameter after preceding exposures. CONCLUSIONS: ONS dilation commences rapidly after pressure exposure with a predictable time course over 3-4 min. Elasticity changes presumably affecting trabecular structures cause upward shifts of the optic nerve sheath pressure response. Clinically, ONSD shifts should be considered in serial measurements for increasing intracranial pressure monitoring, but relevant response delays are absent for lower or higher changes of intracranial pressure.

Fast peroxydisulfate oxidation of the antibiotic norfloxacin catalyzed by cyanobacterial biochar.

Peroxydisulfate (PDS) is a common oxidant for organic contaminant remediation. PDS is typically activated by metal catalysts to generate reactive radicals. Unfortunately, as radicals are non-selective and metal catalysts may cause secondary contamination, alternative selective non-radical pathways and non-metal catalysts need attention. Here we investigated PDS oxidation of commonly detected antibiotic Norfloxacin (NOR) using cyanobacterial nitrogen rich biochars (CBs) as catalysts. NOR was fully degraded by CB pyrolysed at 950 °C (CB950) within 120 min. CB950 caused threefold faster degradation than low pyrolysis temperature (PT) CBs and achieved a maximum surface area normalized rate constant of 4.38 × 10-2 min-1 m-2 L compared to widely used metal catalysts. CB950 maintained full reactivity after four repeated uses. High defluorination (82%) and mineralization (>82%) were observed for CB950/PDS. CBs were active over a broad pH range (3-10), but with twice as high rates under alkaline compared with neutral conditions. NOR is degraded by organic, •OH and SO4•- radicals in low PT CBs/PDS systems, where the presence of MnII promotes radical generation. Electron transfer reactions with radicals supplemented dominate high PT CBs/PDS systems. This study demonstrates high PT biochars from algal bloom biomass may find use as catalysts for organic contaminant oxidation.

Optic Nerve Sheath Viscoelastic Properties: Re-Examination of Biomechanical Behavior and Clinical Implications.

BACKGROUND: Meta-analyses show a variable relationship between optic nerve sheath diameter (ONSD) and the presence of raised intracranial pressure (ICP). Because optic nerve sheath (ONS) tissue can be deformed, it is possible that ONSD reflects not only the current ICP but also prior deforming biomechanical exposures. In this post hoc analysis of two published data sets, we characterize ONS Young's modulus (E, mechanical stress per unit of strain) and calculate threshold pressure for plastic deformation. METHODS: The authors of two previously published articles contributed primary data for these unique post hoc analyses. Human cadaveric ex vivo measurements of ONSD (n = 10) and luminal distending pressure (range 5 to 65 mm Hg) were used to calculate E and the threshold pressure for plastic deformation. Clinical in vivo measurements of ONSD and ICP during endotracheal tube suction from patients with traumatic brain injury (n = 15) were used to validate the ex vivo cadaveric findings. RESULTS: Ex vivo ONS estimate of E was 140 ± 1.3 mm Hg (mean ± standard error), with evidence of plastic deformation occurring with distending pressure at 45 mm Hg. Similar E (71 ± 10 mm Hg) was estimated in vivo with an average ICP of 34 ± 2 mm Hg. CONCLUSIONS: Ex vivo, ONS plastic deformation occurs at levels of pressure commonly seen in patients with raised ICP, leading to distortion of the ICP-ONSD relationship. This evidence of plastic deformation may illustrate why meta-analyses fail to identify a single threshold in ONSD associated with the presence of raised ICP. Future studies characterizing time-dependent viscous characteristics of the ONS will help determine the time course of ONS tissue biomechanical behavior.

Delirium on stroke units: a prospective, multicentric quality-improvement project.

BACKGROUND: Post-stroke delirium (POD) in patients on stroke units (SU) is associated with an increased risk for complications and poorer clinical outcome. The objective was to reduce the severity of POD by implementing an interprofessional delirium-management. METHODS: Multicentric quality-improvement project on five SU implementing a delirium-management with pre/post-comparison. Primary outcome was severity of POD, assessed with the Nursing Delirium Screening Scale (Nu-DESC). Secondary outcome parameters were POD incidence, duration, modified Rankin Scale (mRS), length of stay in SU and hospital, mortality, and others. RESULTS: Out of a total of 799 patients, 59.4% (n = 475) could be included with 9.5% (n = 45) being delirious. Implementation of a delirium-management led to reduced POD severity; Nu-DESC median: pre: 3.5 (interquartile range 2.6-4.7) vs. post 3.0 (2.2-4.0), albeit not significant (p = 0.154). Other outcome parameters were not meaningful different. In the post-period, delirium-management could be delivered to 75% (n = 18) of delirious patients, and only 24 (53.3%) of delirious patients required pharmacological treatments. Patients with a more severe stroke and POD remained on their disability levels, compared to similar affected, non-delirious patients who improved. CONCLUSIONS: Implementation of delirium-management on SU is feasible and can be delivered to most patients, but with limited effects. Nursing interventions as first choice could be delivered to the majority of patients, and only the half required pharmacological treatments. Delirium-management may lead to reduced severity of POD but had only partial effects on duration of POD or length of stay. POD hampers rehabilitation, especially in patients with more severe stroke. REGISTRY: DRKS, DRKS00021436. Registered 04/17/2020, www.drks.de/DRKS00021436 .

Occurrence and stability of ptesculentoside, caudatoside and ptaquiloside in surface waters.

The illudane glycosides ptesculentoside (PTE), caudatoside (CAU) and ptaquiloside (PTA) are found in bracken ferns (Pteridium sp.). PTA is known to contaminate water bodies adjacent to bracken ferns and hence contribute to water toxicity. This study for the first time reports the presence of PTE and CAU in surface waters with concentrations up to 5.3 µg L-1 and outlines their stability under semi-natural conditions using water of two diverse lakes at their natural pH or pH adjusted to 6.5, with temperature controlled at 5 or 15 °C, and in the presence or absence of microbial activity. Under the same set of tested conditions the three illudane glycosides degraded at similar rates: with half-lives of approximately two days at pH 7.4 and 15 °C, and approximately 12 days at pH 5.2-6.5 and 5 °C. The water origin had significant influence on the degradation rates, but only due to its difference in pH. In most cases, the degradation rates of all the three illudane glycosides could be predicted using the existing first-order model for PTA hydrolysis. As PTE and CAU exhibit the same leaching pattern and stability as PTA, previous predictions of bracken environmental impact are likely underestimated, as PTE and CAU have not been monitored and included in the risk assessment.

[Pitfalls in the diagnosis of delirium]. / Fallstricke in der Diagnostik des Delirs.

BACKGROUND: The diagnosis of delirium is challenging and requires precise definitions in both clinical routine and in studies. AIM: To point out various pitfalls in the clinical diagnosis of delirium and discuss solutions. METHODS: Review. RESULTS: Common problems include (a) clinical judgment of staff vs. the use of valid assessment tools, (b) different lists of criteria for delirium that may consider the symptoms of delirium differently and thus lead to inclusion or exclusion of patients, (c) different assessment tools that test the symptoms of delirium to different extents and thus have different accuracy, (d) patients with limited communication abilities, such as aphasia, where common tests often fail and alternative procedures may be more effective; (e) the decision whether to test delirium once, twice, three times, or more frequently in 24 h has consequences on the incidence and duration of delirium, (f) the end of delirium, often defined retrospectively as a delirium-free interval or prospectively as the time of transfer or occurrence of an exclusion criterion, can lead to considerable measurement inaccuracies. CONCLUSIONS: Although not all problems can be definitively answered, transparent definition, performance, and documentation of diagnostic procedures are recommended.

[Disorientation and delirium assessment : A secondary analysis of a prospective, observational study]. / Bedeutung der Desorientierung bei der Delireinschätzung : Sekundäranalyse einer prospektiven, observationellen Studie.

Disorientation may present as a warning sign of developing delirium. The most commonly used delirium assessment tool in Germany, the Confusion Assessment Method for Intensive Care Unit (CAM-ICU), does not rate "disorientation", since intubated patients cannot communicate verbally. However, the majority of German ICU patients are not orally intubated, so they could be examined for their orientation. This study was carried out to investigate whether the delirium feature "disorientation" in extubated patients yields diverging findings in comparison to the CAM-ICU and whether the sensitivity of the CAM-ICU may be improved when combined with the feature "disorientation" (CAM-IMC). A total of 86 paired assessments were completed in 50 extubated patients. Delirium was found in 19.8% (N = 17). The CAM-ICU had a sensitivity of 71% (95% confidence interval [CI] 44-90%) and a specificity of 100% (95-100%). Disorientation, if taken as the only delirium feature, had a sensitivity of 77% (50-93%) and a specificity of 93% (89-100%). The CAM-IMC reached a sensitivity of 88% (64-99%) and a specificity of 100% (95-100%). The receiver operating characteristics (ROC) analyses found an area under the curve (AUC) of 0.941 (95%CI 0.851-1.000) for the CAM-IMC, which was the highest compared to the other delirium tests (CAM-ICU, AUC 0.853 [0.720-0.986]; disorientation, AUC 0.868 [0.745-0.991]). This research emphasizes the importance of the feature "disorientation" for delirium assessments in patients able to verbally communicate and explains some controversial delirium ratings in daily practice. The CAM-IMC appears to be an attractive tool for delirium assessment in nonintubated patients and deserves further research.

Biochar catalyzed dechlorination - Which biochar properties matter?

Bone char catalyzed dechlorination of trichloroethylene (TCE) by green rust (iron(II)-iron(III) hydroxide, GR) has introduced a promising new reaction platform for degradation of chlorinated solvents. This study aimed to reveal whether a broader class of biochars are catalytically active for the dechlorination reaction and to identify which biochar properties are the most important for the catalytic activity. Biochars produced by pyrolysis of animal, plant, and sewage waste substrates at 950 °C were prepared for catalytic dechlorination of TCE by GR tested in batch experiments with 0.15 g L-1 biochar, 3.2 g L-1 GR, and ~ 20 µM TCE. The results showed that the biochar substrate significantly affects its catalytic activity, with the highest TCE reduction rate observed for bone and shrimp-based biochars (k ≥ 0.18 h-1), whereas no reactivity was seen for graphite and activated carbon references. Multivariate regression indicated that the biochar catalytic activity is controlled by multiple biochar properties - biochar surface area, TCE sorption, abundance of C-O groups, and pore size are the properties that impact the catalytic activity most. Derivation of biochar reactivity relationship for a broad spectrum of biochars provides a new approach for identifying proper biochar catalysts for pollutant degradation.

The invasive butterbur contaminates stream and seepage water in groundwater wells with toxic pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are persistent mutagenic and carcinogenic compounds produced by many common plant species. Health authorities recommend minimising human exposure via food and medicinal products to ensure consumer health and safety. However, there is little awareness that PAs can contaminate water resources. Therefore, no regulations exist to limit PAs in drinking water. This study measured a PA base concentration of ~ 70 ng/L in stream water adjacent to an invasive PA-producing plant Petasites hybridus (Asteraceae). After intense rain the PA concentration increased tenfold. In addition, PAs measured up to 230 ng/L in seepage water from groundwater wells. The dominant PAs in both water types corresponded to the most abundant PAs in the plants (senkirkine, senecionine, senecionine N-oxide). The study presents the first discovery of persistent plant toxins in well water and their associated risks. In addition, it for the first time reports monocrotaline and monocrotaline N-oxide in Petasites sp.

Bone Char Mediated Dechlorination of Trichloroethylene by Green Rust.

Biochars function as electron transfer mediators and thus catalyze redox transformations of environmental pollutants. A previous study has shown that bone char (BC) has high catalytic activity for reduction of chlorinated ethylenes using layered Fe(II)-Fe(III) hydroxide (green rust) as reductant. In the present study, we studied the rate of trichloroethylene (TCE) reduction by green rust in the presence of BCs obtained at pyrolysis temperatures (PTs) from 450 to 1050 °C. The reactivity increased with PT, yielding a maximum pseudo-first-order rate constant (k) of 2.0 h-1 in the presence of BC pyrolyzed at 950 °C, while no reaction was seen for BC pyrolyzed at 450 °C. TCE sorption, specific surface area, extent of graphitization, carbon content, and aromaticity of the BCs also increased with PT. The electron-accepting capacity (EAC) of BC peaked at PT of 850 °C, and EAC was linearly correlated with the sum of concentrations of quinoid, quaternary N, and pyridine-N-oxide groups measured by XPS. Moreover, no TCE reduction was seen with graphene nanoparticles and graphitized carbon black, which have high degrees of graphitization but low EAC values. Further analyses showed that TCE reduction rates are well correlated with the EAC and the C/H ratio (proxy of electrical conductivity) of the BCs, strongly indicating that both electron-accepting functional groups and electron-conducting domains are crucial for the BC catalytic reactivity. The present study delineates conditions for designing redox-reactive biochars to be used for remediation of sites contaminated with chlorinated solvents.

Rare earth elements in surface specific urban runoff in Northern Beijing.

Rare earth elements (REEs) have been increasingly diffused to the environment through mining activities and the extensive use in modern commodities, vehicular activities, coal burning and various environmental and agricultural applications. Studies of REEs in urban environments are limited with no data on REEs in urban runoff. To investigate the concentration and distribution of REEs, a total of 150 runoff samples were collected from trafficked areas, rooftops and residential parking lots in a moderate to densely populated area in Beijing, China. The runoff samples were separated into dissolved and particulate phases and analyzed by ICP-MS. The REEs were mainly (>80%) found in the runoff particulate material. The sum of REEs (ΣREE) total concentrations in urban stormwater runoff samples ranged from 0.16 to 185 µg/l. The observed mean total concentration of ΣREE in the runoff samples were 3-14 folds higher and dissolved fractions 1.5 to 6 times higher than published concentrations for recipients such as sewage channels and rivers. The distribution of REEs in runoff was dominated by light REE. Cluster analysis and Pearson's correlations revealed a strong association between the individual REEs pointing to a similar source. Higher Ce concentrations compared to other REEs indicated strong influence from traffic emission particulates. The La/Sm (5.90-8.05), La/Ce (0.53-0.58) and Ce/Yb (31.0-42.7) ratios pointed to REE sources from traffic emissions and coal burning thus defining an urban fingerprint.

Fast LC-MS quantification of ptesculentoside, caudatoside, ptaquiloside and corresponding pterosins in bracken ferns.

Ptaquiloside (PTA) is an illudane glycoside partly responsible for the carcinogenicity of bracken ferns (Pteridium sp.). The PTA analogues ptesculentoside (PTE) and caudatoside (CAU) have similar biochemical reactivity. However, both compounds are highly under-investigated due to the lack of analytical standards and appropriate methods. This study presents a robust method for preparation of analytical standards of PTE, CAU, PTA, the corresponding hydrolysis products: pterosins G, A and B, and an LC-MS based method for simultaneous quantification of the six compounds in bracken. The chromatographic separation of analytes takes 5 min. The observed linear range of quantification was 20-500 µg/L for PTA and pterosin B, and 10-250 µg/L for the remaining compounds (r > 0.999). The limits of detection were 0.08-0.26 µg/L for PTE, CAU and PTA and 0.01-0.03 µg/L for the pterosins, equivalent to 2.0-6.5 µg/g and 0.25-0.75 µg/g in dry weight, respectively. The method was applied on 18 samples of dried fern leaves from 6 continents. Results demonstrated high variation in concentrations of PTE, CAU and PTA with levels prior to hydrolysis up to 3,900, 2,200 and 2,100 µg/g respectively. This is the first analytical method for simultaneous and direct measurement of all six compounds. Its application demonstrated that bracken ferns contain significant amounts of PTE and CAU relative to PTA.