[Interdisciplinary, collaborative D-A-CH (Germany, Austria and Switzerland) consensus statement concerning the diagnostic and treatment of myalgic encephalomyelitis/chronic fatigue syndrome]. / Interdisziplinäres, kollaboratives D-A-CH Konsensus-Statement zur Diagnostik und Behandlung von Myalgischer Enzephalomyelitis/Chronischem Fatigue-Syndrom.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, loss of ability to work and the need for nursing care including artificial nutrition and, in very severe cases, even death.The aim of this D-A-CH (Germany, Austria, Switzerland) consensus statement is 1) to summarize the current state of knowledge on ME/CFS, 2) to highlight the Canadian Consensus Criteria (CCC) as clinical criteria for diagnostics with a focus on the leading symptom post-exertional malaise (PEM) and 3) to provide an overview of current options and possible future developments, particularly with regard to diagnostics and therapy. The D-A-CH consensus statement is intended to support physicians, therapists and valuer in diagnosing patients with suspected ME/CFS by means of adequate anamnesis and clinical-physical examinations as well as the recommended clinical CCC, using the questionnaires and other examination methods presented. The overview of the two pillars of therapy for ME/CFS, pacing and symptom-relieving therapy options, is intended not only to provide orientation for physicians and therapists, but also to support decision-makers from healthcare policy and insurance companies in determining which therapy options should already be reimbursable by them at this point in time for the indication ME/CFS.

Volumetric measurement of intracranial meningiomas: a comparison between linear, planimetric, and machine learning with multiparametric voxel-based morphometry methods.

PURPOSE: To compare the accuracy of three volumetric methods in the radiological assessment of meningiomas: linear (ABC/2), planimetric, and multiparametric machine learning-based semiautomated voxel-based morphometry (VBM), and to investigate the relevance of tumor shape in volumetric error. METHODS: Retrospective imaging database analysis at the authors' institutions. We included patients with a confirmed diagnosis of meningioma and preoperative cranial magnetic resonance imaging eligible for volumetric analyses. After tumor segmentation, images underwent automated computation of shape properties such as sphericity, roundness, flatness, and elongation. RESULTS: Sixty-nine patients (85 tumors) were included. Tumor volumes were significantly different using linear (13.82 cm3 [range 0.13-163.74 cm3]), planimetric (11.66 cm3 [range 0.17-196.2 cm3]) and VBM methods (10.24 cm3 [range 0.17-190.32 cm3]) (p < 0.001). Median volume and percentage errors between the planimetric and linear methods and the VBM method were 1.08 cm3 and 11.61%, and 0.23 cm3 and 5.5%, respectively. Planimetry and linear methods overestimated the actual volume in 79% and 63% of the patients, respectively. Correlation studies showed excellent reliability and volumetric agreement between manual- and computer-based methods. Larger and flatter tumors had greater accuracy on planimetry, whereas less rounded tumors contributed negatively to the accuracy of the linear method. CONCLUSION: Semiautomated VBM volumetry for meningiomas is not influenced by tumor shape properties, whereas planimetry and linear methods tend to overestimate tumor volume. Furthermore, it is necessary to consider tumor roundness prior to linear measurement so as to choose the most appropriate method for each patient on an individual basis.

[Increase of educational inequity at the transformation to higher secondary schools in connection with the COVID-19 pandemic: low achievers and low motivated students as particular risk group]. / Zunahme von Bildungsungerechtigkeit durch die COVID-19-Pandemie beim Übergang in die Sekundarstufe II: Leistungsschwache und wenig motivierte Schüler*innen als besonders vulnerable Gruppe.

When learning at home, students face higher demands in regards of self-regulated learning compared to learning at school. In order to cope with the demands of distance learning, high levels of self-management, self-motivation, and self-organization are required. This can be-according to the resource model of coping with developmental tasks (Fend et al. 2009)-supported by familial, school-related and personal resources. Based upon this theoretical approach, a survey was conducted with 593 students just after their transition to upper secondary schools in autumn 2021 on distance learning and relevant resources. They spent about one month in the new school before they had to cope with a 4-month long period of distance learning. Four regression models were estimated using step-wise inclusion of the different resources described in the paper. The analyses confirm above all the great importance of personal resources (academic achievement, learning motivation, general self-efficacy) for coping with the demands of distance learning. Low achievers and low motivated students prove to be particularly at risk in the context of distance learning. Therefore, this vulnerable group requires special attention and support both, in future periods of remote teaching as well as following the pandemic.

Predicting Coping With Self-Regulated Distance Learning in Times of COVID-19: Evidence From a Longitudinal Study.

Due to the COVID-19 pandemic, students worldwide have experienced fundamental changes to their learning. Schools had to shift to distance education as part of the effort to stop the spread of the virus. Although distance learning undoubtedly resulted in challenges for all students, there is much concern that it exacerbated existing educational inequalities and led to disadvantages - particularly for students who were already struggling academically and lacking support from family and school. The aim of this paper was to investigate the possible impact of family and child characteristics, school performance prior to lockdown, and support at home and from school during lockdown in coping with self-regulated distance learning during times of COVID-19. The paper draws on data from a two-wave longitudinal study surveying 155 lower secondary school students aged 13-14years from a rural-alpine region in Austria. Data were collected 1year before the start of the pandemic and directly after schools had returned to in-class teaching after the first lockdown. Our findings support the notion that distance learning poses a substantial risk for exacerbating existing educational disadvantages. They show that coping with out-of-school learning was especially challenging for students with low academic achievement and learning motivation prior to the pandemic. Furthermore, findings demonstrate that the support from parents and teachers foster students' capabilities to cope with the self-regulatory demands connected with distance learning. Although the importance of competencies for self-regulated learning became particularly evident in the context of the pandemic, from our findings, it can be concluded that in the future, schools should strengthen their investment in promoting competencies for self-regulated learning. Self-regulation must be recognized as an essential educational skill for academic achievement and life-long learning.

Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin.

In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with α-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.

Molecular basis of F-actin regulation and sarcomere assembly via myotilin.

Sarcomeres, the basic contractile units of striated muscle cells, contain arrays of thin (actin) and thick (myosin) filaments that slide past each other during contraction. The Ig-like domain-containing protein myotilin provides structural integrity to Z-discs-the boundaries between adjacent sarcomeres. Myotilin binds to Z-disc components, including F-actin and α-actinin-2, but the molecular mechanism of binding and implications of these interactions on Z-disc integrity are still elusive. To illuminate them, we used a combination of small-angle X-ray scattering, cross-linking mass spectrometry, and biochemical and molecular biophysics approaches. We discovered that myotilin displays conformational ensembles in solution. We generated a structural model of the F-actin:myotilin complex that revealed how myotilin interacts with and stabilizes F-actin via its Ig-like domains and flanking regions. Mutant myotilin designed with impaired F-actin binding showed increased dynamics in cells. Structural analyses and competition assays uncovered that myotilin displaces tropomyosin from F-actin. Our findings suggest a novel role of myotilin as a co-organizer of Z-disc assembly and advance our mechanistic understanding of myotilin's structural role in Z-discs.

Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin.

The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin-binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+ Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin-binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.

Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation.

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X-ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle-based systems.

Dual-porous cellulose nanofibril aerogels via modular drying and cross-linking.

Nanofibrillar foams and aerogels are traditionally either macroporous with low surface area and high mechanical strength, or mesoporous with high surface area and low mechanical strength. In this work, an anionic cellulose nanofibril (CNF)-based dual-porous aerogel with BET specific surface area up to 430 m2 g-1 was prepared via a modular process combining directional freeze-thawing (creating macro-pores, ca. 50-200 µm) and supercritical drying (creating meso-pores, ca. 2-50 nm). Furthermore, by optionally utilizing both physical and chemical cross-linking strategies, aerogels with a Young's modulus of up to 711 kPa and good stability in aqueous conditions were demonstrated. By altering cross-linking strategies, the properties of resulting aerogels, such as hydrophilicity, mechanical strength and stability in water, can be precisely controlled for different applications. As a result, cationic methylene blue (MB) and metal ions (Ag+) were chosen as model species to investigate the absorption properties of the physically cross-linked aerogels in water. The aerogels showed a maximum adsorption of MB up to 234 mg g-1 and of Ag+ up to 116 mg g-1 as a result of the high specific surface area of the aerogels and their strong electrostatic interaction with the model species. Importantly, the hierarchical dual porosity of the aerogels enabled fast adsorption kinetics combined with a considerable adsorption capacity overall. Finally, it was shown that the adsorbed Ag+ could be converted to metallic Ag, demonstrating the additional functionality of these dual porous hybrid aerogels for antibacterial or catalytic applications.

Multi-element chemical analysis of printed circuit boards - challenges and pitfalls.

Printed circuit boards (PCB) are an essential component of electrical and electronic equipment (EEE) and account for roughly 5% of the mass of EEE. Knowledge about the chemical composition of PCB is crucial to enable an enhanced recycling, especially for elements considered critical regarding their economic importance and supply risk (e.g. precious metals or specialty metals such as tantalum, germanium, gallium). No standard reference methods exist for determining the chemical composition of PCB. Previously published element mass fractions cover a wide range and were produced with numerous methods for sample preparation, digestion, and measurement. This impedes comparability of PCB composition from different studies. To investigate sample- and element-specific effects of applied methods a PCB sample from desktop PC was analysed in two separate labs. One lab applied sample- and element-specific validated methods (aqua regia, HF, H2SO4 blend; ICP-OES, QQQ-ICP-MS), providing reference values, the other applied routine in-house methods (aqua regia; ICP-OES, ICP-MS) to assess the validity of in-house methods for chemical analysis of PCB. A t-test was used to identify elements depicting significant differences between validated and in-house methods. For base metals, in-house methods led to comparable results. For precious, specialty, and hazardous metals as well as REE investigated in this study, significant differences were detected. With respect to all results for in-house methods in this study, the combination of aqua regia and ICP-OES led to less significant differences than aqua regia and ICP-MS. The results show that sample- and element-specific quality assurance is crucial to prevent analytical bias.

Refractive indices of layers and optical simulations of Cu(In,Ga)Se2 solar cells.

Cu(In,Ga)Se2 based solar cells have reached efficiencies close to 23%. Further knowledge-driven improvements require accurate determination of the material properties. Here, we present refractive indices for all layers in Cu(In,Ga)Se2 solar cells with high efficiency. The optical bandgap of Cu(In,Ga)Se2 does not depend on the Cu content in the explored composition range, while the absorption coefficient value is primarily determined by the Cu content. An expression for the absorption spectrum is proposed, with Ga and Cu compositions as parameters. This set of parameters allows accurate device simulations to understand remaining absorption and carrier collection losses and develop strategies to improve performances.

Agglomeration potential of TiO2 in synthetic leachates made from the fly ash of different incinerated wastes.

Material flow studies have shown that a large fraction of the engineered nanoparticles used in products end up in municipal waste. In many countries, this municipal waste is incinerated before landfilling. However, the behavior of engineered nanoparticles (ENPs) in the leachates of incinerated wastes has not been investigated so far. In this study, TiO2 ENPs were spiked into synthetic landfill leachates made from different types of fly ash from three waste incineration plants. The synthetic leachates were prepared by standard protocols and two types of modified procedures with much higher dilution ratios that resulted in reduced ionic strength. The pH of the synthetic leachates was adjusted in a wide range (i.e. pH 3 to 11) to understand the effects of pH on agglomeration. The experimental results indicated that agglomeration of TiO2 in the synthetic landfill leachate simultaneously depend on ionic strength, ionic composition and pH. However, when the ionic strength was high, the effects of the other two factors were masked. The zeta potential of the particles was directly related to the size of the TiO2 agglomerates formed. The samples with an absolute zeta potential value < 10 mV were less stable, with the size of TiO2 agglomerates in excess of 1500 nm. It can be deduced from this study that TiO2 ENPs deposited in the landfill may be favored to form agglomerates and ultimately settle from the water percolating through the landfill and thus remain in the landfill.

Determination of non-gaseous and gaseous mercury fractions in unused fluorescent lamps: a study of different lamp types.

Since incandescent light bulbs have been phased out in the European Union from 2009, the use of fluorescent lamps has drastically increased as a reliable, more energy-efficient and cost-effective alternative. State-of-the-art fluorescent lamps are dependent on mercury/mercury alloys, posing a risk for the consumer and the environment, and appropriate waste management is challenging. Consequently analytical methods to determine possible mercury species (non-gaseous/gaseous) in these lamps are of need. Here, a straightforward and wet-chemistry-based analytical strategy for the determination of gaseous and non-gaseous mercury in commercially available fluorescent lamps is presented. It can be adapted in any analytical laboratory, without or with only minimum modifications of already installed equipment. The analytical figures of merit, as well as application of the method to a series of commercially available fluorescent lamps, are presented. Out of 14 analysed and commercially available lamp types, results from this study indicate that only one contains a slightly higher amount of mercury than set by the legislative force. In all new lamps the amount of gaseous mercury is negligible compared with the non-gaseous fraction (88%-99% of total mercury).

The structure and regulation of human muscle α-actinin.

The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. α-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa α-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level. The structure provides insight into the phosphoinositide-based mechanism controlling its interaction with sarcomeric proteins such as titin, lays a foundation for studying the impact of pathogenic mutations at molecular resolution, and is likely to be broadly relevant for the regulation of spectrin-like proteins.

Direct interaction of actin filaments with F-BAR protein pacsin2.

Two mechanisms have emerged as major regulators of membrane shape: BAR domain-containing proteins, which induce invaginations and protrusions, and nuclear promoting factors, which cause generation of branched actin filaments that exert mechanical forces on membranes. While a large body of information exists on interactions of BAR proteins with membranes and regulatory proteins of the cytoskeleton, little is known about connections between these two processes. Here, we show that the F-BAR domain protein pacsin2 is able to associate with actin filaments using the same concave surface employed to bind to membranes, while some other tested N-BAR and F-BAR proteins (endophilin, CIP4 and FCHO2) do not associate with actin. This finding reveals a new level of complexity in membrane remodeling processes.

Recalibration of the auditory continuity illusion: sensory and decisional effects.

An interrupted sound can be perceived as continuous when noise masks the interruption, creating an illusion of continuity. Recent findings have shown that adaptor sounds preceding an ambiguous target sound can influence listeners' rating of target continuity. However, it remains unclear whether these aftereffects on perceived continuity influence sensory processes, decisional processes (i.e., criterion shifts), or both. The present study addressed this question. Results show that the target sound was more likely to be rated as 'continuous' when preceded by adaptors that were perceived as clearly discontinuous than when it was preceded by adaptors that were heard (illusorily or veridically) as continuous. Detection-theory analyses indicated that these contrastive aftereffects reflect a combination of sensory and decisional processes. The contrastive sensory aftereffect persisted even when adaptors and targets were presented to opposite ears, suggesting a neural origin in structures that receive binaural inputs. Finally, physically identical but perceptually ambiguous adaptors that were rated as 'continuous' induced more reports of target continuity than adaptors that were rated as 'discontinuous'. This assimilative aftereffect was purely decisional. These findings confirm that judgments of auditory continuity can be influenced by preceding events, and reveal that these aftereffects have both sensory and decisional components.

The continuity illusion adapts to the auditory scene.

The human auditory system is efficient at restoring sounds of interest. In noisy environments, for example, an interrupted target sound may be illusorily heard as continuing smoothly when a loud noise masks the interruptions. In quiet environments, however, sudden interruptions might signal important events. In that case, restoration of the target sound would be disadvantageous. Achieving useful perceptual stability may require the restoration mechanism to adapt its output to current perceptual demands, a hypothesis which has not yet been fully evaluated. In this study, we investigated whether auditory restoration depends on preceding auditory scenes, and we report evidence that restoration adapts to the perceived continuity of target sounds and to the loudness of interrupting sounds. In the first experiment, listeners adapted to illusory and non-illusory tone sweeps (targets) and interrupting noise, and we observed that the perceived continuity of the target and the loudness of the interrupting noise influenced the extent of subsequent restorations. A second experiment revealed that these adaptation effects were unrelated to the adapted spectra, indicating that non-sensory representations of the perceived auditory scene were involved. We argue that auditory restoration is a dynamic illusory phenomenon which recalibrates continuity hearing to different acoustic environments.

Oncogenic c-H-ras deregulates survivin expression: an improvement for survival.

Survivin protein accomplishes two basic functions: cell cycle regulation and control of apoptosis. It is only expressed in G2/M phase and it influences rescue pathways in apoptosis-induced cells. Overexpression of constitutive active c-H-ras in HeLa, or induction of c-H-ras in a stable HeLaDiR cell line, led to sustained survivin expression in all cell cycle phases and even protected cells from drug induced apoptosis. siRNA-mediated silencing of survivin reversed this protection. Here we link the anti-apoptotic property of survivin to its cell cycle (in)dependent regulation via the activity of oncogenic c-H-ras.