Decoding the RNA virome of the tree parasite Armillaria provides new insights into the viral community of soil-borne fungi.

The globally distributed basidiomycete genus Armillaria includes wood decomposers that can act as opportunistic parasites, causing deadly root rot on woody plants. To test whether RNA viruses are involved in this opportunistic behaviour, a large isolate collection of five Armillaria species collected over 40 years in Switzerland from trees, dead wood and soil was analysed. De novo assembly of RNA-Seq data revealed 21 viruses, 14 of which belong to putative new species. Two dsRNA viruses and an unclassified Tymovirales are formally described for the first time for Armillaria. One mitovirus occurred with a high prevalence of 71.1%, while all other viruses were much less prevalent (0.6%-16.9%). About half of all viruses were found only in one fungal species, others occurred in 2-6 fungal species. Co-infections of 2-7 viruses per isolate were not uncommon (34.9%), and most viruses persisted circulating within fungal populations for decades. Some viruses were related to viruses associated with other Armillaria species, supporting the hypothesis that virus transmission can occur between different fungal species. Although no specific correlation between viruses and the fungal trophic strategy was found, this study opens new insights into viral diversity hidden in the soil microbiome.

Plasma Concentrations of Tranylcypromine in Depressed Patients With Chronic Kidney Disease: Two Case Reports.

PURPOSE: The prevalence of comorbid depression and chronic kidney disease (CKD) is high. The aim of this brief report was to review 2 cases of treatment with tranylcypromine (TCP) in patients with treatment-resistant depression (TRD) and CKD. Tests of the plasma concentration of TCP were included. METHODS: Medical and psychiatric notes of the 2 patients were reviewed with plasma concentrations of TCP as a key aspect of the discussion. The data are evaluated in the context of relevant medical and pharmacokinetic literature. FINDINGS: Plasma concentrations of TCP are highly variable both in patients with and without CKD. Plasma concentrations of TCP were not increased in the 2 cases with CKD as compared with literature data of patients without CKD. No signs of intoxication were detected in 2 cases with CKD that impaired continuous treatment of depression with TCP. IMPLICATIONS: TCP may be considered in selected cases of TRD with concomitant CKD. More clinical data and tests of plasma concentrations of TCP are needed in patients with CKD.

Possible Biological Control of Ash Dieback Using the Mycoparasite Hymenoscyphus Fraxineus Mitovirus 2.

Invasive fungal diseases represent a major threat to forest ecosystems worldwide. As the application of fungicides is often unfeasible and not a sustainable solution, only a few other control options are available, including biological control. In this context, the use of parasitic mycoviruses as biocontrol agents of fungal pathogens has recently gained particular attention. Since the 1990s, the Asian fungus Hymenoscyphus fraxineus has been causing lethal ash dieback across Europe. In the present study, we investigated the biocontrol potential of the mitovirus Hymenoscyphus fraxineus mitovirus 2 (HfMV2) previously identified in Japanese populations of the pathogen. HfMV2 could be successfully introduced via co-culturing into 16 of 105 HfMV2-free isolates. Infection with HfMV2 had contrasting effects on fungal growth in vitro, from cryptic to detrimental or beneficial. Virus-infected H. fraxineus isolates whose growth was reduced by HfMV2 showed overall a lower virulence on ash (Fraxinus excelsior) saplings as compared with their isogenic HfMV2-free lines. The results suggest that mycoviruses exist in the native populations of H. fraxineus in Asia that have the potential for biological control of ash dieback in Europe. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Effect of Underlayer Quality on Microstructure, Stoichiometry, and Magnetic Properties of Hexaferrite BaFe12O19 Grown on YSZ(111) by Pulsed Laser Deposition.

We have studied the effect of platinum underlayer for two deposited thicknesses on the microstructure, crystalline quality, morphology, chemical composition, and magnetic properties as well as magnetic domain formation of BaFe12O19 (BaM) grown on YSZ(111) by pulsed laser deposition (PLD). We found that PLD platinum deposited with a thickness of 25 nm cannot withstand the dewetting phenomenon occurring during the subsequent BaM layer growth. A smooth and continuous Pt underlayer that possesses a sharp interface and omits the intermixing between the BaM and substrate was successfully achieved for a deposited Pt film thickness of 75 nm. Independent of the thickness of the deposited Pt layer, the c-axis orientation as well as coercivity Hc and the anisotropy HA fields were significantly improved due to a remarkable improvement of lattice mismatch in comparison with the BaM layer grown without a Pt underlayer on YSZ(111). By applying high-resolution X-ray diffraction, scanning and transmission electron microscopy (SEM/TEM), and atomically resolved scanning TEM imaging combined with energy-dispersive X-ray spectroscopy, as well as atomic and magnetic force microscopy, a comprehensive investigation of both structure and chemical composition of the deposited BaM films and their interfacial regions was performed. This study aimed to correlate the enhancement of the overall magnetic properties and of the local spin magnetic domain orientation with the modification of BaM microstructure and chemical composition at the nanometer scale due to the Pt underlayer. Finally, we attempted to understand the mechanisms that control the magnetic properties of these BaM films in order to be able to tailor them.

[Psychopharmacotherapy with the MAO-inhibitor Tranylcypromine Key Aspects and Trends in Theory and Practice]. / Psychopharmakotherapie mit dem MAO-Hemmer Tranylcypromin Schwerpunkte und Trends aus Theorie und Praxis.

The irreversible monoamine oxidase inhibitor tranylcypromine has been known as an antidepressant drug for more than 60 years. The aim of this review was to make an assessment of the state of the art and therapy of tranylcypromine. The recent medical-scientific literature is analyzed and discussed with respect to key aspects of and general trends in practical psychopharmacotherapy. Meta-analyses of controlled clinical studies have shown that tranylcypromine is an established approach to treatment-resistant depression. Doses (maximum dose, maintenance dose) are increasingly adapted to the requirements of treatment-resistant depression. Monoamine oxidase is not only the primary pharmacological target of tranylcypromine but determines for the first doses also the pharmacokinetics of tranylcypromine because monoamine oxidase is also an enantioselective drug-metabolizing enzyme of the monoamine oxidase inhibitor. An increased diversity of the antidepressant pharmacotherapy suggests the need to rethink the continuing assessment of tranylcypromine as a therapeutic "ultima ratio" in depression. In conclusion, tranylcypromine as a drug of second choice remains a valuable option in antidepressant treatment. Criteria of a switch from other antidepressant drugs to tranylcypromine should be better defined.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Insufficient recovery of monoamine oxidase in a bioequivalence study of the monoamine oxidase inhibitor tranylcypromine: Recommendation of the tranylcypromine enantiomer test.

OBJECTIVE: To investigate the recovery of monoamine oxidase (MAO) activity in the liver and gut of healthy subjects after a dose of 10 mg of the irreversible MAO inhibitor tranylcypromine (TCP). MATERIALS AND METHODS: A bioequivalence study of TCP with a wash-out of 1 week between 2 doses of 10 mg TCP was re-analyzed for changes of the plasma concentrations of TCP enantiomers. Plasma concentrations of (+)-TCP and the ratio of (+)-TCP and (-)-TCP plasma concentrations were used as a measure of MAO activity because (+)-TCP is a more effective suicide inhibitor of MAO than (-)-TCP and, therefore considerably more metabolized by MAO. RESULTS: The area under the curve from the first to the last measured concentration (AUCt) and the maximum plasma concentration (Cmax) of (+)-TCP increased significantly in the second dose (p < 0.0001) by 43.1% (11.8%) and 66.5% (26.4%), respectively, (mean with 95%CI in each case). The ratios (+)-TCP/(-)-TCP of AUCt and Cmax also increased significantly (p < 0.0001) by 27.3% (6.4%) and 25.9% (6.2%), respectively. No changes were found for the half-lives (T1/2) of both enantiomers. CONCLUSION: For the first dose, MAO is the main drug-metabolizing enzyme of (+)-TCP. MAO activity in the liver and gut is not completely recovered within 1 week after 1 dose of TCP. One week of wash-out may be insufficient in bioequivalence studies of irreversible MAO inhibitors. Prolonged inhibition of MAO after the treatment with irreversible MAO inhibitors may explain drug interactions during the switch from another MAO inhibitor to TCP. Enantiomer plasma concentrations of TCP after a dose of racemic TCP may be used as a test for gastrointestinal and hepatic MAO activity.

Efficacy and Adverse Effects of Tranylcypromine and Tricyclic Antidepressants in the Treatment of Depression: A Systematic Review and Comprehensive Meta-analysis.

PURPOSE: We conducted a comprehensive meta-analysis of the comparison of tranylcypromine (TCP) and tricyclic antidepressants (TCAs) in the treatment of depression because such work is lacking in medical scientific literature. METHODS: Literature was searched for studies of TCP controlled by TCAs in multiple databases and in reviews of TCP and monoamine oxidase inhibitors. The natural logarithm of the odds ratio (logOR) and the pooled logOR according to a fixed effect model were calculated for the numbers of responders and nonresponders. RESULTS: A total of 227 studies of TCP were found including 75 controlled studies of TCP-monotherapy. Twelve of 23 studies of TCP monotherapy and TCAs were excluded for several reasons (duplicates, safety studies, retrospective, cross-over), leaving 11 prospective and parallel controlled studies of TCP monotherapy versus TCAs (6 randomized double-blind). One study was excluded from the meta-analysis because of low quality of study design according to the Food and Drug Administration guidelines of studies of antidepressant drugs and high risk of bias according to the Cochrane's tool. Two studies with equal efficacy of TCP and TCAs in continuous endpoints did not provide dichotomous response data. A pooled logOR of 0.480 (95% confidence interval, 0.105-0.857, P = 0.01) resulted for the remaining eight studies in the primary meta-analysis, which favors TCP significantly over TCAs (test for heterogeneity: Х = 8.1, df = 7, P > 0.3, not heterogenous; I = 13.6%, heterogeneity not important). The result is robust with respect to inclusion of hypothetical response data of the 2 studies with continuous data only: pooled logOR, 0.350 (95% confidence interval, 0.028-0.672, P = 0.03). Visual inspection of forest plots and subgroup analysis suggest that superiority of TCP over TCAs is determined by 2 studies in psychomotor-retarded (anergic) depression. CONCLUSIONS: Tranylcypromine and TCAs have an equal antidepressant effect in a mean sample of depressed patients with mixed psychomotor symptoms. Tranylcypromine might be superior to TCAs in depression with predominant psychomotor retardation.

[Therapeutic drug monitoring in neuropsychopharmacology : Summary of the consensus guidelines 2017 of the TDM task force of the AGNP]. / Therapeutisches Drug-Monitoring in der Neuropsychopharmakologie : Zusammenfassung der Konsensusleitlinien 2017 der TDM-Arbeitsgruppe der AGNP.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood serum or plasma to optimize pharmacological therapy. TDM is an instrument with which the high interindividual variability of pharmacokinetics of patients can be identified and therefore enables a personalized pharmacotherapy. In September 2017 the TDM task force of the Working Group for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update of the consensus guidelines on TDM published in 2011. This article summarizes the essential statements for the clinical practice in psychiatry and neurology.

Monitoring the thin film formation during sputter deposition of vanadium carbide.

The thin film formation of magnetron sputtered polycrystalline coatings was monitored by in situ X-ray reflectivity measurements. The measured intensity was analyzed using the Parratt algorithm for time-dependent thin film systems. Guidelines for the on-line interpretation of the data were developed. For thick coatings, the experimental resolution needs to be included in the data evaluation in order to avoid misinterpretations. Based on a simple layer model, the time-dependent mean electron density, roughness and growth velocity were extracted from the data. As an example, the method was applied to the hard coating material vanadium carbide. Both instantaneous and slowly varying changes of the coating could be detected. It was shown that the growth velocity is proportional to the DC power. Significant changes of the microstructure induced by the working gas pressure are mainly driven by the chemical composition.

Relevance of Platinum Underlayer Crystal Quality for the Microstructure and Magnetic Properties of the Heterostructures YbFeO3/Pt/YSZ(111).

The hexagonal ferrite h-YbFeO3 grown on YSZ(111) by pulsed laser deposition is foreseen as a promising single multiferroic candidate where ferroelectricity and antiferromagnetism coexist for future applications at low temperatures. We studied in detail the microstructure as well as the temperature dependence of the magnetic properties of the devices by comparing the heterostructures grown directly on YSZ(111) (i.e., YbPt_Th0nm) with h-YbFeO3 films deposited on substrates buffered with platinum Pt/YSZ(111) and in dependence on the Pt underlayer film thickness (i.e., YbPt_Th10nm, YbPt_Th40nm, YbPt_Th55nm, and YbPt_Th70nm). The goal was to deeply understand the importance of the crystal quality and morphology of the Pt underlayer for the h-YbFeO3 layer crystal quality, surface morphology, and the resulting physical properties. We demonstrate the relevance of homogeneity, continuity, and hillock formation of the Pt layer for the h-YbFeO3 microstructure in terms of crystal structure, mosaicity, grain boundaries, and defect distribution. The findings of transmission electron microscopy and X-ray diffraction reciprocal space mapping characterization enable us to conclude that an optimum film thickness for the Pt bottom electrode is ThPt = 70 nm, which improves the crystal quality of h-YbFeO3 films grown on Pt-buffered YSZ(111) in comparison with h-YbFeO3 films grown on YSZ(111) (i.e., YbPt_Th0nm). The latter shows a disturbance in the crystal structure, in the up-and-down atomic arrangement of the ferroelectric domains, as well as in the Yb-Fe exchange interactions. Therefore, an enhancement in the remanent and in the total magnetization was obtained at low temperatures below 50 K for h-YbFeO3 films deposited on Pt-buffered substrates Pt/YSZ(111) when the Pt underlayer reached ThPt = 70 nm.

Dependence of the Structural and Magnetic Properties on the Growth Sequence in Heterostructures Designed by YbFeO3 and BaFe12O19.

The structure and the chemical composition of individual layers as well as of interfaces belonging to the two heterostructures M1 (BaFe12O19/YbFeO3/YSZ) and M2 (YbFeO3/BaFe12O19/YSZ) grown by pulsed laser deposition on yttria-stabilized zirconia (YSZ) substrates are deeply characterized by using a combination of methods such as high-resolution X-ray diffraction, transmission electron microscopy (TEM), and atomic-resolution scanning TEM with energy-dispersive X-ray spectroscopy. The temperature-dependent magnetic properties demonstrate two distinct heterostructures with different coercivity, anisotropy fields, and first anisotropy constants, which are related to the defect concentrations within the individual layers and to the degree of intermixing at the interface. The heterostructure with the stacking order BaFe12O19/YbFeO3, i.e., M1, exhibits a distinctive interface without any chemical intermixture, while an Fe-rich crystalline phase is observed in M2 both in atomic-resolution EDX maps and in mass density profiles. Additionally, M1 shows high c-axis orientation, which induces a higher anisotropy constant K1 as well as a larger coercivity due to a high number of phase boundaries. Despite the existence of a canted antiferromagnetic/ferromagnetic combination (T < 140 K), both heterostructures M1 and M2 do not reveal any detectable exchange bias at T = 50 K. Additionally, compressive residual strain on the BaM layer is found to be suppressing the ferromagnetism, thus reducing the Curie temperature (Tc) in the case of M1. These findings suggest that M1 (BaFe12O19/YbFeO3/YSZ) is suitable for magnetic storage applications.

Structural and Morphological Studies of Pt in the As-Grown and Encapsulated States and Dependency on Film Thickness.

The morphology and crystal structure of Pt films grown by pulsed laser deposition (PLD) on yttria-stabilized zirconia (YSZ)at high temperatures Tg = 900 °C was studied for four different film thicknesses varying between 10 and 70 nm. During the subsequent growth of the capping layer, the thermal stability of the Pt was strongly influenced by the Pt film's thickness. Furthermore, these later affected the film morphology, the crystal structure and hillocks size, and distribution during subsequent growth at Tg = 900 °C for a long duration. The modifications in the morphology as well as in the structure of the Pt film without a capping layer, named also as the as-grown and encapsulated layers in the bilayer system, were examined by a combination of microscopic and scattering methods. The increase in the thickness of the deposited Pt film brought three competitive phenomena into occurrence, such as 3D-2D morphological transition, dewetting, and hillock formation. The degree of coverage, film continuity, and the crystal quality of the Pt film were significantly improved by increasing the deposition time. An optimum Pt film thickness of 70 nm was found to be suitable for obtaining a hillock-free Pt bottom electrode which also withstood the dewetting phenomena revealed during the subsequent growth of capping layers. This achievement is crucial for the deposition of functional bottom electrodes in ferroelectric and multiferroic heterostructure systems.

Detuning-dependent Mollow triplet of a coherently-driven single quantum dot.

We present both experimental and theoretical investigations of a laser-driven quantum dot (QD) in the dressed-state regime of resonance fluorescence. We explore the role of phonon scattering and pure dephasing on the detuning-dependence of the Mollow triplet and show that the triplet sidebands may spectrally broaden or narrow with increasing detuning. Based on a polaron master equation approach, which includes electron-phonon interaction nonperturbatively, we derive a fully analytical expression for the spectrum. With respect to detuning dependence, we identify a crossover between the regimes of spectral sideband narrowing or broadening. We also predict regimes of phonon-induced squeezing and anti-squeezing of the spectral resonances. A comparison of the theoretical predictions to detailed experimental studies on the laser detuning-dependence of Mollow triplet resonance emission from single In(Ga)As QDs reveals excellent agreement.

Antidepressant treatment with MAO-inhibitors during general and regional anesthesia: a review and case report of spinal anesthesia for lower extremity surgery without discontinuation of tranylcypromine.

Monoamine oxidase-(MAO)-inhibitors are a treatment of last resort in treatment resistant depression, which is regarded as a condition of increased psychiatric risk. General and regional anesthesia for elective surgery during use of long-term MAO-inhibitors remains a matter of debate because of an increased risk of drug interactions and decreased sympathetic stability. A series of case reports and new comparative studies reveal the safety of anesthesia/analgesia in non-cardiac surgery without discontinuation of the MAO-inhibitor if best effort is made for maintenance of sympathetic homeostasis and if known drug interactions are avoided. Very few reports with severe adverse incidents have been noted. Severe cardiovascular morbidity, a contraindication of MAO-inhibitors, probably contributed to peri- and postoperative complications. According to new studies, the risk of pharmacokinetic drug interactions is lower for tranylcypromine than for phenelzine. In the present case, a 66-year-old psychiatric patient on permanent treatment with 20 mg/day tranylcypromine was admitted for forefoot surgery. Anesthetic premedication consisted of 7.5 mg oral midazolam. Intravenous midazolam (0.5 mg) was dispensed for intraoperative sedation. After local anesthesia of the puncture site with 30 mg isobar prilocaine, spinal anesthesia was achieved by a single shot of 13.5 mg hyperbar bupivacaine (0.5%) intrathecally. Postoperative regional and general analgesia were accomplished by a peripheral nerve block with 50 mg isobar bupivacaine as well as oral etoricoxib and oxycodone. No peri- or postoperative complications were encountered. It is concluded that general or regional anesthesia for noncardiac surgery without discontinuation of MAO-inhibitor treatment may be a safe intervention after careful evaluation of an individual's perioperative and psychiatric risk. The increased psychiatric risk in patients treated with MAO-inhibitors outweighs the increased, however manageable, perioperative risk from continuing treatment during surgery.

Process Development of a Generative Method for Partial and Controlled Integration of Active Substances into Open-Porous Matrix Structures.

A special generative manufacturing (AM) process was developed for the partial integration of active ingredients into open-porous matrix structures. A mixture of a silver-containing solution as an antibacterial material with an alginate hydrogel as a carrier system was produced as the active ingredient. The AM process developed was used to introduce the active ingredient solution into an open-porous niobium containing a ß-titanium matrix structure, thus creating a reproducible active ingredient delivery system. The matrix structure had already been produced in a separate AM process by means of selective laser melting (SLM). The main advantage of this process is the ability to control porosity with high precision. To determine optimal surface conditions for the integration of active ingredients into the matrix structure, different surface conditions of the titanium substrate were tested for their impact on wetting behaviour of a silver-containing hydrogel solution. The solution-substrate contact angle was measured and evaluated to determine the most favourable surface condition. To develop the generative manufacturing process, an FDM printer underwent modifications that permitted partial application of the drug solution to the structure in accordance with the bioprinting principle. The modified process enabled flexible control and programming of both the position and volume of the applied drug. Furthermore, the process was able to fill up to 95% of the titanium matrix body pore volume used. The customised application of drug carriers onto implants as a drug delivery system can be achieved via the developed process, providing an alternative to established methods like dip coating that lack this capability.

Modular deposition chamber for in situ X-ray experiments during RF and DC magnetron sputtering.

A new sputtering system for in situ X-ray experiments during DC and RF magnetron sputtering is described. The outstanding features of the system are the modular design of the vacuum chamber, the adjustable deposition angle, the option for plasma diagnostics, and the UHV sample transfer in order to access complementary surface analysis methods. First in situ diffraction and reflectivity measurements during RF and DC deposition of vanadium carbide demonstrate the performance of the set-up.