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Abstract While magnetomyography (MMG) using optically pumped magnetometers (OPMs) is a promising method for non-invasive investigation of the neuromuscular system, it has almost exclusively been performed in magnetically shielded rooms (MSRs) to date. MSRs provide extraordinary conditions for biomagnetic measurements but limit the widespread adoption of measurement methods due to high costs and extensive infrastructure. In this work, we address this issue by exploring the feasibility of mobile OPM-MMG in a setup of commercially available components. From field mapping and simulations, we find that the employed zero-field OPM can operate within a large region of the mobile shield, beyond which residual magnetic fields and perturbations become increasingly intolerable. Moreover, with digital filtering and moderate averaging a signal quality comparable to that in a heavily shielded MSR is attained. These findings facilitate practical and cost-effective implementations of OPM-MMG systems in clinical practice and research.

Abstract Background Idiopathic (IF) and nonidiopathic facial (NIF) nerve palsies are the most common forms of peripheral facial nerve palsies. Various risk factors for IF palsies, such as weather, have been explored, but such associations are sparse for NIF palsies, and it remains unclear whether certain diagnostic procedures, such as contrast agent-enhanced cerebral magnetic resonance imaging (cMRI), are helpful in the differential diagnosis of NIF vs. IF. Methods In this retrospective, monocentric study over a five-year period, the medical reports of 343 patients with peripheral facial nerve palsy were analysed based on aetiology, sociodemographic factors, cardiovascular risk factors, consultation time, diagnostic procedures such as cMRI, and laboratory results. We also investigated whether weather conditions and German Google Trends data were associated with the occurrence of NIF. To assess the importance of doctors’ clinical opinions, the documented anamneses and clinical examination reports were presented and rated in a blinded fashion by five neurology residents to assess the likelihood of NIF. Results A total of 254 patients (74%) had IF, and 89 patients (26%) had NIF. The most common aetiology among the NIF patients was the varicella zoster virus (VZV, 45%). Among the factors analysed, efflorescence (odds ratio (OR) 17.3) and rater agreement (OR 5.3) had the highest associations with NIF. The day of consultation (Friday, OR 3.6) and the cMRI findings of contrast enhancement of the facial nerve (OR 2.3) were also risk factors associated with NIF. In contrast, the local weather, Google Trends data, and cardiovascular risk factors were not associated with NIF. Conclusion The findings of this retrospective study highlight the importance of patient history and careful inspections to identify skin lesions for the differential diagnosis of acute facial nerve palsy. Special caution is advised for hospital physicians during the tick season, as a surge in NIF cases can lead to a concomitant increase in IF cases, making it challenging to choose adequate diagnostic methods.

Abstract Optically pumped magnetometers (OPM) are quantum sensors that offer new possibilities to measure biomagnetic signals. Compared to the current standard surface electromyography (EMG), in magnetomyography (MMG), OPM sensors offer the advantage of contactless measurements of muscle activity. However, little is known about the relative performance of OPM-MMG and EMG, e.g. in their ability to detect and classify finger movements. To address this in a proof-of-principle study, we recorded simultaneous OPM-MMG and EMG of finger flexor muscles for the discrimination of individual finger movements on a single human participant. Using a deep learning model for movement classification, we found that both sensor modalities were able to discriminate finger movements with above 89% accuracy. Furthermore, model predictions for the two sensor modalities showed high agreement in movement detection (85% agreement; Cohen’s kappa: 0.45). Our findings show that OPM sensors can be employed for contactless discrimination of finger movements and incentivize future applications of OPM in magnetomyography.

There is no general consensus on evaluating disease progression in facioscapulohumeral muscular dystrophy (FSHD). Recently, shear wave elastography (SWE) has been proposed as a noninvasive diagnostic tool to assess muscle stiffness in vivo. Therefore, this study aimed to characterize biceps brachii (BB) muscle mechanics in mild-FSHD patients using SWE. Eight patients with mild FSHD, the BB were assessed using SWE, surface electromyography (sEMG), elbow moment measurements during rest, maximum voluntary contraction (MVC), and isometric ramp contractions at 25%, 50%, and 75% MVC across five elbow positions (60°, 90°, 120°, 150°, and 180° flexion). The mean absolute percentage deviation (MAPD) was analyzed as a measure of force control during ramp contractions. The shear elastic modulus of the BB in FSHD patients increased from flexed to extended elbow positions (e.g., p < 0.001 at 25% MVC) and with increasing contraction intensity (e.g., p < 0.001 at 60°). MAPD was highly variable, indicating significant deviation from target values during ramp contractions. SWE in mild FSHD is influenced by contraction level and joint angle, similar to findings of previous studies in healthy subjects. Moreover, altered force control could relate to the subjective muscle weakness reported by patients with dystrophies.

Abstract Aging leads to a decline in muscle mass and force-generating capacity. Ultrasound shear wave elastography (SWE) is a non-invasive method to capture age-related muscular adaptation. This study assessed biceps brachii muscle (BB) mechanics, hypothesizing that shear elastic modulus reflects (i) passive muscle force increase imposed by length change, (ii) activation-dependent mechanical changes, and (iii) differences between older and younger individuals. Fourteen healthy volunteers aged 60–80 participated. Shear elastic modulus, surface electromyography, and elbow torque were measured at five elbow positions in passive and active states. Data collected from young adults aged 20–40 were compared. The BB passive shear elastic modulus increased from flexion to extension, with the older group exhibiting up to 52.58% higher values. Maximum elbow flexion torque decreased in extended positions, with the older group 23.67% weaker. Significant effects of elbow angle, activity level, and age on total and active shear elastic modulus were found during submaximal contractions. The older group had 20.25% lower active shear elastic modulus at 25% maximum voluntary contraction. SWE effectively quantified passive and activation-dependent BB mechanics, detecting age-related alterations at rest and during low-level activities. These findings suggest shear elastic modulus as a promising biomarker for identifying altered muscle mechanics in aging.

Abstract Pressure recovery (PR) is essential part of the post stenotic fluid mechanics and depends on the ratio of EOA/AA, the effective aortic valve orifice area (EOA) and aortic cross-sectional area (AA). In patients with advanced ascending aortic aneurysm and mildly diseased aortic valves, the effect of AA on pressure recovery and corresponding functional aortic valve opening area (ELCO) was evaluated before and after valve-sparing surgery (Dacron graft implantation). 66 Patients with ascending aortic aneurysm (mean aortic diameter 57 +/− 10 mm) and aortic valve-sparing surgery (32 reimplantation technique (David), 34 remodeling technique (Yacoub)) were routinely investigated by Doppler echocardiography. Dacron graft with a diameter between 26 and 34 mm were implanted. EOA was significantly declined after surgery (3.4 +/− 0.8 vs. 2.6 +/− 0.9cm2; p

Neuromuscular disorders (NMDs) affect various parts of a motor unit, such as the motor neuron, neuromuscular junction, and muscle fibers. Abnormal spontaneous activity (SA) is detected with electromyography (EMG) as an essential hallmark in diagnosing NMD, which causes fatigue, pain, and muscle weakness. Monitoring the effects of NMD calls for new smart devices to collect and classify EMG. Delay-based Reservoir Computing (DRC) is a neuromorphic algorithm with high efficiency in classifying sequential data. This work proposes a new DRC-based algorithm that provides a reference for medical education and training and a second opinion to clinicians to verify NMD diagnoses by detecting SA in muscles. With a sampling frequency of Fs = 64 kHz, we have classified SA with EMG signals of 1 s of muscle recordings. Furthermore, the DRC model of size N = 600 nodes has successfully detected SA signals against normal muscle activity with an accuracy of up to 90.7%. The potential of using neuromorphic processing approaches in point-of-care diagnostics, alongside the supervision of a clinician, provides a more comprehensive and reliable clinical profile. Our developed model benefits from the potential to be implemented in physical hardware to provide near-sensor edge computing.

Abstract Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects. Many templates have a small field-of-view typically focussed on the brain, limiting the use for applications requiring detailed information about other extra-cranial structures in the head and neck area. However, there are several applications where such information is important, for example source reconstruction of electroencephalography (EEG) and/or magnetoencephalography (MEG). We have constructed a new template based on 225 T1w and FLAIR images with a big field-of-view that can serve both as target for across subject spatial normalization as well as a basis to build high-resolution head models. This template is based on and iteratively re-registered to the MNI152 space to provide maximal compatibility with the most commonly used brain MRI template.

Objective: Emergency diagnostics, such as acquisition of an electroencephalogram (EEG), are of great diagnostic importance, but there is often a lack of experienced personnel. Wet active electrode sponge-based electroencephalogram (sp-EEG) systems can be applied rapidly and by inexperienced personnel. This makes them an attractive alternative to routine EEG (r-EEG) systems in these settings. Here, we examined the feasibility and signal quality of sp-EEG compared to r-EEG. Methods: In this case-control, single-blind, non-randomized study, EEG recordings using a sp- and a r-EEG system were performed in 18 individuals with a variety of epileptiform discharges and 11 healthy control subjects. The time was stopped until all electrodes in both systems displayed adequate skin-electrode impedances. The resulting 58 EEGs were visually inspected by 7 experienced, blinded neurologists. Raters were asked to score physiological and pathological graphoelements, and to distinguish between the different systems by visual inspection of the EEGs. Results: Time to signal acquisition for sp-EEG was significantly faster (4.8 min (SD 2.01) vs. r-EEG 13.3 min (SD 2.72), p

Neuromuscular diseases are a prevalent cause of prolonged and severe suffering for patients, and with the global population aging, it is increasingly becoming a pressing concern. To assess muscle activity in NMDs, clinicians and researchers typically use electromyography (EMG), which can be either non-invasive using surface EMG, or invasive through needle EMG. Surface EMG signals have a low spatial resolution, and while the needle EMG provides a higher resolution, it can be painful for the patients, with an additional risk of infection. The pain associated with the needle EMG can pose a risk for certain patient groups, such as children. For example, children with spinal muscular atrophy (type of NMD) require regular monitoring of treatment efficacy through needle EMG; however, due to the pain caused by the procedure, clinicians often rely on a clinical assessment rather than needle EMG. Magnetomyography (MMG), the magnetic counterpart of the EMG, measures muscle activity non-invasively using magnetic signals. With super-resolution capabilities, MMG has the potential to improve spatial resolution and, in the meantime, address the limitations of EMG. This article discusses the challenges in developing magnetic sensors for MMG, including sensor design and technology advancements that allow for more specific recordings, targeting of individual motor units, and reduction of magnetic noise. In addition, we cover the motor unit behavior and activation pattern, an overview of magnetic sensing technologies, and evaluations of wearable, non-invasive magnetic sensors for MMG.

The STX1B gene encodes the presynaptic protein syntaxin-1B, which plays a major role in regulating fusion of synaptic vesicles. Mutations in STX1B are known to cause epilepsy syndromes, such as genetic epilepsies with febrile seizures plus (GEFS+). Here, we reprogrammed skin fibroblasts from a female patient affected by GEFS+ to human induced pluripotent stem cells (iPSCs). The patient carries an InDel mutation (c.133_134insGGATGTGCATTG; p.Lys45delinsArgMetCysIleGlu and c.135_136AC > GA; p.Leu46Met), located in the regulatory Habc-domain of STX1B. Successful reprogramming of cells was confirmed by a normal karyotype, expression of several pluripotency markers and the potential to differentiate into all three germ layers.

Background and objectives: Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes. Methods: We performed a diffusion MRI mega-analysis in 192 participants consisting of 126 controls and 66 patients with GGE from four different cohorts and two different epilepsy centers. We applied whole-brain multi-site harmonization and analyzed fractional anisotropy (FA), as well as mean, radial and axial diffusivity (MD/RD/AD) to assess differences between controls, patients with GGE and the common GGE subtypes, i.e. GGE with generalized tonic-clonic seizures only (GGE-GTCS), GGE-JME and absence epilepsy (GGE-AE). We also analyzed relationships with patients' response to anti-seizure-medication (ASM). Results: Relative to controls, we identified decreased anisotropy and increased RD in patients with GGE. We found no significant effects of disease duration, age of onset or seizure frequency on diffusion metrics. Patients with JME had increased MD and RD when compared to controls, while patients with GGE-GTCS showed decreased MD/AD when compared to controls. Compared to patients with GGE-AE, patients with GGE-GTCS had lower AD/MD. Compared to patients with GGE-GTCS, patients with GGE-JME had higher MD/RD and AD. Moreover, we found lower FA in patients with refractory when compared to patients with non-refractory GGE in the right cortico-spinal tract, but no significant differences in patients with active versus controlled epilepsy. Discussion: We provide evidence that clinically defined GGE as a whole and GGE-subtypes harbor marked microstructural differences detectable with diffusion MRI. Moreover, we found an association between microstructural changes and treatment resistance. Our findings have important implications for future full-resolution multi-site studies when assessing GGE, its subtypes and ASM refractoriness.

Abstract Relevant pressure recovery (PR) has been shown to increase functional stenotic aortic valve orifice area and reduce left ventricular load. However, little is known about the relevance of PR in the pulmonary artery. The study examined the impact of PR using 2D‐echocardiography in the pulmonary artery distal to the degenerated homograft in patients after Ross surgery. Ninety‐two patients with pulmonary homograft were investigated by Doppler echocardiography (mean time interval after surgery 31 ± 26 months). PR was measured as a function of pulmonary artery diameter determined by computed tomography angiography. Homograft orifice area, valve resistance, and transvalvular stroke work were calculated with and without considering PR. PR decreased as the pulmonary artery diameter increased (r = −0.69, p

Optically pumped magnetometers (OPM) are quantum sensors that enable the contactless, non-invasive measurement of biomagnetic muscle signals, i.e., magnetomyography (MMG). Due to the contactless recording, OPM-MMG might be preferable to standard electromyography (EMG) for patients with neuromuscular diseases, particularly when repetitive recordings for diagnostic and therapeutic monitoring are mandatory. OPM-MMG studies have focused on recording physiological muscle activity in healthy individuals, whereas research on neuromuscular patients with pathological altered muscle activity is non-existent. Here, we report a proof-of-principle study on the application of OPM-MMG in patients with neuromuscular diseases. Specifically, we compare the muscular activity during maximal isometric contraction of the left rectus femoris muscle in three neuromuscular patients with severe (Transthyretin Amyloidosis in combination with Pompe’s disease), mild (Charcot-Marie-Tooth disease, type 2), and without neurogenic, but myogenic, damage (Myotonia Congenita). Seven healthy young participants served as the control group. As expected, and confirmed by using simultaneous surface electromyography (sEMG), a time-series analysis revealed a dispersed interference pattern during maximal contraction with high amplitudes. Furthermore, both patients with neurogenic damage (ATTR and CMT2) showed a reduced variability of the MMG signal, quantified as the signal standard deviation of the main component of the frequency spectrum, highlighting the reduced possibility of motor unit recruitment due to the loss of motor neurons. Our results show that recording pathologically altered voluntary muscle activity with OPM-MMG is possible, paving the way for the potential use of OPM-MMG in larger studies to explore the potential benefits in clinical neurophysiology.

The design of and materials for prosthodontic abutments and posts have significant influences on the fracture resistance of restored teeth. This in vitro study compared the fracture strength and marginal quality of full-ceramic crowns as a function of the inserted root posts via simulation of a five-year period of use. Test specimens were prepared from 60 extracted maxillary incisors using titanium L9 (A), glass-fiber L9 (B), and glass-fiber L6 (C) root posts. The circular marginal gap behavior, linear loading capacity, and material fatigue after artificial aging were investigated. The marginal gap behavior and material fatigue were analyzed using electron microscopy. The linear loading capacity of the specimens was investigated using the Zwick Z005 universal testing machine. None of the tested root post materials showed statistically significant differences in marginal width values (p = 0.921), except in the case of marginal gap location. For Group A, there was a statistically significant difference from the labial to the distal (p = 0.012), mesial (p = 0.000), and palatinal (p = 0.005). Similarly, Group B showed a statistically significant difference from the labial to the distal (p = 0.003), mesial (p = 0.000), and palatinal (p = 0.003). Group C showed a statistically significant difference from the labial to the distal (p = 0.001) and mesial (p = 0.009). Linear load capacity reached mean values of 455.8–537.7 N, and micro-cracks occurred after artificial aging, predominantly in Groups B and C. Through the chosen experimental design, it was shown that the root post material and root post length had no influence on the fracture strength of the test teeth before or after artificial aging. However, the marginal gap location depends on the root post material and its length, which is wider mesially and distally and also tends to be greater palatinally than labially.

Myasthenia gravis (MG) is often accompanied with muscle weakness; however, little is known about mechanical adaptions of the affected muscles. As the latter can be assessed using ultrasound shear wave elastography (SWE), this study characterizes the biceps brachii muscle of 11 patients with MG and compares them with that of 14 healthy volunteers. Simultaneous SWE, elbow torque and surface electromyography measurements were performed during rest, maximal voluntary contraction (MVC) and submaximal isometric contractions (up to 25%, 50% and 75% MVC) at different elbow angles from flexion to extension. We found that, with increasing elbow angle, maximum elbow torque decreased (p < 0.001), whereas muscle stiffness increased during rest (p = 0.001), MVC (p = 0.004) and submaximal contractions (p < 0.001). Muscle stiffness increased with increasing contraction intensities during submaximal contractions (p < 0.001). In comparison to the healthy cohort, muscle stiffness of MG patients was 2.1 times higher at rest (p < 0.001) but 8.93% lower in active state (75% MVC, p = 0.044). We conclude that (i) increased muscle stiffness shown by SWE during rest might be an indicator of MG, (ii) SWE reflects muscle weakness and (iii) SWE can be used to characterize MG muscle.

We present the case of a patient with granulomatous endocarditis of the mitral valve leading to severe valve stenosis caused by granulomatosis with polyangiitis. Endocarditis is a rare complication of granulomatosis with polyangiitis that may be misdiagnosed as infectious endocarditis or, as in our case, thrombotic lesions. (Level of Difficulty: Intermediate.)

Very few reports exist on serious cardiac complications associated with intake of serotonin-noradrenaline reuptake inhibitors. This paper describes and discusses the case of a patient who ingested a dose of 17.5 g venlafaxine. She developed a full serotonergic syndrome leading to multi-organ failure, including refractory cardiovascular shock, which was managed by early implantation of an extracorporeal life support (ECLS) system as a bridging strategy. This intervention was successful and resulted in full recovery of the patient.

Abstract Background Acute hyperammonemia without signs of common causes in the elderly might be challenging to identify. We report the oldest case known to date of a female patient with late onset ornithine carbamyltransferase deficiency (OTC), which was unmasked after a protein overload due to nutritional supplements. Our case illustrates how environmental factors (protein overload) in previously unknown OTC in the elderly leads to hyperammonemic encephalopathy and highlights that early treatment prevents persisting neurological deficits and should be considered in absence of common causes of hyperammonemic encephalopathy. Case presentation A 68-year-old woman presented with acute confusion, which progressed into a deep coma (Glasgow-Coma-Scale score 3) within a few hours. The only remarkable finding was a plasma ammonia (NH3) concentration of 697 μmmol/l (range 12–47 μmmol/). Third party history revealed that the patient disliked meat for most of her life (meat = protein, which needs to be metabolized) and had taken nutritional supplements (since supplements often have a high protein-ratio) 2 days before the symptoms started. Protein catabolism results in NH3, which is metabolized via the urea cycle. Consequently, the acute hyperammonemia in our patient was thought to be related to an inherited metabolic disorder, which only unmasked itself as a result of an overload of the corresponding metabolite (in this case protein). Since ornithine carbamyltransferase deficiency (OTC) is the most common inherited urea cycle disorder, this diagnosis became likely and was confirmed later via genetic and metabolic testing (amino acids, orotic acid, etc.). After 2 weeks of treatment (dialysis, low-protein-diet, nitrogen-lowering medication) the patient was discharged in a healthy condition without any neurological deficits. Conclusion OTC is a x-chromosomal linked disorder, that usually manifests in newborn infants and children, but also rarely in adults and even rarer in the elderly (50- till 60-years-old), where it is probably underdiagnosed. In case of hyperammonemic encephalopathy – regardless of the underlying cause -, treatment should be started early to prevent persisting neurological deficits. OTC should be considered in absence of common causes of hyperammonemic encephalopathy.

Rigidity in Parkinson’s disease (PD) is assessed by clinical scales, mostly the Unified Parkinson’s Disease Rating Scale of the Movement Disorders Society (MDS-UPDRS). While the MDS-UPDRS-III ranges on an integer from 0 to 4, we investigated whether muscle ultrasound shear wave elastography (SWE) offers a refined assessment. Ten PD patients (five treated with deep brain stimulation (DBS) and levodopa, five with levodopa only) and ten healthy controls were included. Over a period of 80 min, both the SWE value and the item 22b-c of the MDS-UPDRS-III were measured at 5 min intervals. The measurements were performed bilaterally at the biceps brachii muscle (BB) and flexor digitorum profundus muscle in flexion and passive extension. Rigidity was modified and tracked under various therapeutic conditions (with and without medication/DBS). The feasibility of SWE for objective quantification was evaluated by correlation with the UPDRS-III: considering all positions and muscles, there was already a weak correlation (r = 0.01, p < 0.001)—in a targeted analysis, the BB in passive extension showed a markedly higher correlation (r = 0.494, p < 0.001). The application of dopaminergic medication and DBS resulted in statistically significant short-term changes in both clinical rigidity and SWE measurements in the BB (p < 0.001). We conclude that rigidity is reflected in the SWE measurements, indicating that SWE is a potential non-invasive quantitative assessment tool for PD.

Ultrasound shear wave elastography (SWE) is an emerging modality for the estimation of stiffness, but it has not been studied in relation to common disorders with altered stiffness, such as bruxism, which affects almost one-third of adults. Because this condition could lead to an increased stiffness of masticatory muscles, we investigated SWE in bruxism according to a proof-of-principle and feasibility study with 10 patients with known bruxism and an age- and gender-matched control group. SWE of the left and right masseter muscles was estimated under three conditions: relaxed jaw, 50% of the subjective maximal bite force, and maximal jaw opening. Rejecting the null hypothesis, SWE was significantly increased during relaxed jaw (bruxism 1.92 m/s ± 0.44; controls 1.66 m/s ± 0.24), whereas for maximal mouth opening, the result was vice versa increased with 2.89 m/s ± 0.93 for bruxism patients compared with 3.53 m/s ± 0.95 in the healthy control, which could be due to limited jaw movement in chronic bruxism patients (bruxism 4.46 m/s ± 1.17; controls 5.23 m/s ± 0.43). We show that SWE in bruxism is feasible and could be of potential use for diagnostics and monitoring, though we also highlight important limitations and necessary methodological considerations for future studies.

So far, surface electromyography (sEMG) has been the method of choice to detect and evaluate muscle fatigue. However, recent advancements in non-cryogenic quantum sensors, such as optically pumped magnetometers (OPMs), enable interesting possibilities to flexibly record biomagnetic signals. Yet, a magnetomyographic investigation of muscular fatigue is still missing. Here, we simultaneously used sEMG (4 surface electrode) and OPM-based magnetomyography (OPM-MMG, 4 sensors) to detect muscle fatigue during a 3 × 1-min isometric contractions of the left rectus femoris muscle in 7 healthy participants. Both signals exhibited the characteristic spectral compression distinctive for muscle fatigue. OPM-MMG and sEMG slope values, used to quantify the spectral compression of the signals, were positively correlated, displaying similarity between the techniques. Additionally, the analysis of the different components of the magnetic field vector enabled speculations regarding the propagation of the muscle action potentials (MAPs). Altogether these results show the feasibility of the magnetomyographic approach with OPMs and propose a potential alternative to sEMG for the study of muscle fatigue.

The main purpose of this study was to synthesize a new set of naphthoquinone-based ruthenium(II) arene complexes and to develop an understanding of their mode of action. This study systematically reviews the steps of synthesis, aiming to provide a simplified approach using microwave irradiation. The chemical structures and the physicochemical properties of this novel group of compounds were examined by 1H-NMR and 13C-NMR spectroscopy, X-ray diffractometry, HPLC-MS and supporting DFT calculations. Several aspects of the biological activity were investigated in vitro, including short- and long-term cytotoxicity tests, cellular accumulation studies, detection of reactive oxygen species generation, apoptosis induction and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity as well as cell cycle analysis in A549, CH1/PA-1, and SW480 cancer cells. Furthermore, the DNA interaction ability was studied in a cell-free assay. A positive correlation was found between cytotoxicity, lipophilicity and cellular accumulation of the tested complexes, and the results offer some important insights into the effects of the arene. The most obvious finding to emerge from this study is that the usually very chemosensitive CH1/PA-1 teratocarcinoma cells showed resistance to these phthiocol-based organometallics in comparison to the usually less chemosensitive SW480 colon carcinoma cells, which pilot experiments suggest as being related to NQO1 activity.

Background: In an ever-aging society, health care systems will be confronted with an increasing number of patients over 80 years (“the very old”). Currently, knowledge about and recommendations for delirium management are often based on studies in patients aged 60 to 65 years. It is not clear whether these findings apply to patients ≥80 years.Aim: Comparison of younger and older patients with delirium, especially regarding risk factors.Methods: In this prospective cohort study, within 1-year, 5,831 patients (18–80 years: n = 4,730; ≥80: n = 1,101) with delirium were enrolled. The diagnosis of delirium was based on the Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM (Diagnostic and Statistical Manual)-5 construct of nursing instrument. Sociodemographic trajectories, as well as the relevant predisposing and precipitating factors for delirium, were assessed via a multiple regression analysis.Results: The very old were more commonly admitted as emergencies (OR 1.42), had a greater mortality risk (OR 1.56) and displayed fewer precipitating risk factors for the development of a delirium, although the number of diagnoses were not different (p = 0.325). Predisposing factors were sufficient almost alone for the development of delirium in patients ≥ 80 years of age; in 18–80 years of age, additional precipitating factors had to occur to make a delirium possible.Conclusion: When relevant predisposing factors for delirium are apparent, patients over 80 years of age require comparatively few or no precipitating factors to develop delirium. This finding should be taken into account at hospitalization and may allow better treatment of delirium in the future.

Ultrasound shear wave elastography (SWE) is an increasingly used imaging modality that expands clinical ultrasound by measuring the elasticity of various tissues, such as the altered elasticity of tumors. Peripheral nerve tumors are rare, have been well-characterized by B-mode-ultrasound, but have not yet been investigated with SWE. Given the lack of studies, a first step would be to investigate homogeneous peripheral nerve tumors (PNTs), histologically neurofibromas or schwannomas, which can occur in multiple in neurofibromatosis type 1 and 2 (NF1 and 2), respectively. Hence, we measured shear wave velocity (SWV) in 30 PNTs of 11 patients with NF1 within the median nerve. The SWV in PNTs ranged between 2.8 ± 0.8 m/s and correlated with their width and approximate volume but not with their length or height. Furthermore, we determined the extent to which PNTs alter the SWV of the median nerve for three positions of the wrist joint: neutral (zero-degree), individual maximal flexion and maximal extension. Here, SWV was decreased in NF1 patients compared to age- and sex-matched controls (p = 0.029) during maximal wrist extension. We speculate that the presence of PNTs may have a biomechanical impact on peripheral nerves which has not been demonstrated yet.

Shear wave elastography (SWE) is a clinical ultrasound imaging modality that enables non-invasive estimation of tissue elasticity. However, various methodological factors—such as vendor-specific implementations of SWE, mechanical anisotropy of tissue, varying anatomical position of muscle and changes in elasticity due to passive muscle stretch—can confound muscle SWE measurements and increase their variability. A measurement protocol with a low variability of reference measurements in healthy subjects is desirable to facilitate diagnostic conclusions on an individual-patient level. Here, we present data from 52 healthy volunteers in the areas of: (1) Characterizing different limb and truncal muscles in terms of inter-subject variability of SWE measurements. Superficial muscles with little pennation, such as biceps brachii, exhibit the lowest variability whereas paravertebral muscles show the highest. (2) Comparing two protocols with different limb positioning in a trade-off between examination convenience and SWE measurement variability. Repositioning to achieve low passive extension of each muscle results in the lowest SWE variability. (3) Providing SWE shear wave velocity (SWV) reference values for a specific ultrasound machine/transducer setup (Canon Aplio i800, 18 MHz probe) for a number of muscles and two positioning protocols. We argue that methodological issues limit the current clinical applicability of muscle SWE.

Abstract Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal-recessive mitochondrial disorder caused by TYMP mutations presenting with a multisystemic, often lethal syndrome of progressive leukoencephalopathy, ophthalmoparesis, demyelinating neuropathy, cachexia and gastrointestinal dysmotility. Hemodialysis (HMD) has been suggested as a treatment to reduce accumulation of thymidine and deoxyuridine. However, all studies so far have failed to measure the toxic metabolites in cerebrospinal fluid (CSF), which is the crucial compartment for CNS damage. Our study is the first prospective, longitudinal investigation, exploiting detailed serial testing of predefined clinical and molecular outcome parameters (including serial CSF assessments) in a 29-year-old MNGIE patient undergoing 1 year of extensive HMD. We demonstrate that HMD only transiently restores increased serum and urine levels of thymidine and deoxyuridine, but fails to reduce CSF levels of the toxic metabolites and is ineffective to influence neurological function. These findings have direct important implications for clinical practice: They prevent a burdensome, long-term invasive, but ultimately probably ineffective procedure in future MNGIE patients.

We present a molecular mechanics force field in AMBER format for the mixed-valence manganese vanadium oxide cluster [Mn4V4O17(OAc)3]3−—a synthetic analogue of the oxygen-evolving complex that catalyzes the water oxidation reaction in photosystem II—with parameter sets for two different oxidation states. Most force field parameters involving metal atoms have been newly parametrized and the harmonic terms refined using hybrid quantum mechanics/molecular mechanics reference simulations, although some parameters were adapted from pre-existing force fields of vanadate cages and manganese oxo dimers. The characteristic Jahn–Teller distortions of d4 MnIII ions in octahedral environments are recovered by the force field. As an application, the developed parameters have been used to calculate the redox potential of the [MnIIIMn3IV] ⇌ [Mn4IV]+e− half-reaction in acetonitrile by means of Marcus theory.

Myotonia, i.e., delayed muscle relaxation in certain hereditary muscle disorders, can be assessed quantitatively using different techniques ranging from force measurements to electrodiagnostics. Ultrasound shear wave elastography (SWE) has been proposed as a novel tool in biomechanics and neuromuscular medicine for the non-invasive estimation of muscle elasticity and, indirectly, muscle force. The aim of this study is to provide ‘proof-of-principle’ that SWE allows a quantitative measurement of the duration of delayed muscle relaxation in myotonia in a simple clinical setting. In six myotonic muscle disorder patients and six healthy volunteers, shear wave velocities (SWV) parallel to the fiber orientation in the flexor digitorum superficialis muscle in the forearm were recorded with a temporal resolution of one per second during fist-clenching and subsequent relaxation; the relaxation time to 10% of normalized shear wave velocity (RT0.1) was calculated. Forty-six SWE imaging sequences were acquired, yielding a mean RT0.1 of 7.38 s in myotonic muscle disorder patients, significantly higher than in healthy volunteers (1.36 s), which is comparable to data obtained by mechanical dynamometry. SWV measurements during the baseline relaxation and voluntary contraction phases did not differ significantly between groups. We conclude that SWE is a promising, non-invasive, widely available tool for the quantitative assessment of myotonia to aid in diagnosis and therapeutic monitoring.

Sulfur-substituted nucleobases are promising photo- and chemotherapeutic drugs. Here, the authors unravel the electronic and structural aspects that lead to the ultrafast population of triplet states in these molecules, providing an explanation for their efficiency as photosensitizers.

Pump-probe measurements aim to capture the motion of electrons and nuclei on their natural timescales (femtoseconds to attoseconds) as chemical and physical transformations take place, effectively making “molecular movies” with short light pulses. However, the quantum dynamics of interest are filtered by the coordinate-dependent matrix elements of the chosen experimental observable. Thus, it is only through a combination of experimental measurements and theoretical calculations that one can gain insight into the internal dynamics. Here, we report on a combination of structural (relativistic ultrafast electron diffraction, or UED) and spectroscopic (time-resolved photoelectron spectroscopy, or TRPES) measurements to follow the coupled electronic and nuclear dynamics involved in the internal conversion and photodissociation of the polyatomic molecule, diiodomethane (CH_{2}I_{2}). While UED directly probes the 3D nuclear dynamics, TRPES only serves as an indirect probe of nuclear dynamics via Franck-Condon factors, but it is sensitive to electronic energies and configurations, via Koopmans’ correlations and photoelectron angular distributions. These two measurements are interpreted with trajectory surface hopping calculations, which are capable of simulating the observables for both measurements from the same dynamics calculations. The measurements highlight the nonlocal dynamics captured by different groups of trajectories in the calculations. For the first time, both UED and TRPES are combined with theory capable of calculating the observables in both cases, yielding a direct view of the structural and nonadiabatic dynamics involved.

The human brain is known to contain several functional networks that interact dynamically. Therefore, it is desirable to analyze the temporal features of these networks by dynamic functional connectivity (dFC). A sliding window approach was used in an event-related fMRI (visual stimulation using checkerboards) to assess the impact of repetition time (TR) and window size on the temporal features of BOLD dFC. In addition, we also examined the spatial distribution of dFC and tested the feasibility of this approach for the analysis of interictal epileptiforme discharges. 15 healthy controls (visual stimulation paradigm) and three patients with epilepsy (EEG-fMRI) were measured with EPI-fMRI. We calculated the functional connectivity degree (FCD) by determining the total number of connections of a given voxel above a predefined threshold based on Pearson correlation. FCD could capture hemodynamic changes relative to stimulus onset in controls. A significant effect of TR and window size was observed on FCD estimates. At a conventional TR of 2.6 s, FCD values were marginal compared to FCD values using sub-seconds TRs achievable with multiband (MB) fMRI. Concerning window sizes, a specific maximum of FCD values (inverted u-shape behavior) was found for each TR, indicating a limit to the possible gain in FCD for increasing window size. In patients, a dynamic FCD change was found relative to the onset of epileptiform EEG patterns, which was compatible with their clinical semiology. Our findings indicate that dynamic FCD transients are better detectable with sub-second TR than conventional TR. This approach was capable of capturing neuronal connectivity across various regions of the brain, indicating a potential to study the temporal characteristics of interictal epileptiform discharges and seizures in epilepsy patients or other brain diseases with brief events.

[This corrects the article DOI: 10.1371/journal.pone.0190480.].

Machine learning (ML) has shown to advance the research field of quantum chemistry in almost any possible direction and has also recently been applied to investigate the multifaceted photochemistry of molecules. In this paper, we pursue two goals: (i) We show how ML can be used to model permanent dipole moments for excited states and transition dipole moments by adapting the charge model of Gastegger et al. [Chem. Sci. 8, 6924–6935 (2017)], which was originally proposed for the permanent dipole moment vector of the electronic ground state. (ii) We investigate the transferability of our excited-state ML models in chemical space, i.e., whether an ML model can predict the properties of molecules that it has never been trained on and whether it can learn the different excited states of two molecules simultaneously. To this aim, we employ and extend our previously reported SchNarc approach for excited-state ML. We calculate UV absorption spectra from excited-state energies and transition dipole moments as well as electrostatic potentials from latent charges inferred by the ML model of the permanent dipole moment vectors. We train our ML models on C H 2 N H 2 + and C2H4, while predictions are carried out for these molecules and additionally for CHNH2, CH2NH, and C 2 H 5 + . The results indicate that transferability is possible for the excited states. [ABSTRACT FROM AUTHOR]