Neuronal and behavioral correlates of the influence of contextual cues on value-based decision making = Die neuronalen und behavioralen Korrelate des Einflusses von kontextuellen Reizen auf das wertebasierte Entscheidungsverhalten : Kumulative Arbeit

Value-based decisions are almost omnipresent in life. However, they are not very well understood. Previous research has shown that the decision-making process is dynamic, and can be influenced, for instance, by increasing the saliency of a certain attribute. Therefore, one could hypothesize that it is possible to make decision-makers aware of certain long-term attributes in order to improve decisions. In four main studies published during my doctoral work, I investigated the role of contextual attributes on value-based decision making and how they influence dietary choices. The text presented here puts the published studies into a broader context and reviews various topics, such as the influence of attention on decision making, neuroscientific evidence as well as computational models in decision-making research

Fluoroapatite/polymer-composite materials based on the microstructure of shark teeth and dulling liquids for intraoral tooth visualization

Ziel der Arbeit war die Entwicklung von biomimetischen synthetischen Fluorapatit/Polymer-Dentalkompositen für die Anwendung als Zahnfüllungsmaterial. Überdies wurden Mattierungsdispersionen entwickelt, um von Zähnen digitale 3D-Modelle zu erzeugen. Als biologische Modellsysteme wurden Haifisch- und Krokodilzähne chemisch, strukturell und mechanisch analysiert. Der Zahnschmelz (Enameloid) der Zähne von rezenten Haifischen besteht aus Fluorapatit, Ca5(PO4)3F, wobei der Fluoridgehalt mit 3,1 Gew% nahezu so hoch ist wie in geologischen Fluorapatit-Kristallen (3,64 Gew%). Enameloid zeigt verglichen mit Dentin eine höhere Kristallinität des Mineralanteils. Die Fluorapatit-Kristallite im Enameloid sind sehr dünn (50-80 nm) und sehr lang (> 1 μm), und ihn Bündeln organisiert. Diese Bündel lassen sich in drei Typen einteilen, die sich in ihrer Orientierung unterscheiden: Es gibt umlaufende, radiale und axiale Kristallitbündel. Jedes Kristallitbündel, unabhängig von seiner Orientierung, ist umhüllt von einer dünnen Schicht einer organischen Matrix. Den äußersten Teil des Enameloids bildet der sogenannte "shiny layer". Dieser besteht im unbehandelten Zustand aus ungeordneten polyedrischen Kristalliten. Obwohl es innerhalb des Enameloids eine starke strukturelle Anisotropie gibt, sind die lokalen mechanischen Eigenschaften weitgehend isotrop. Vickers-Mikrohärtemessungen und Nanoindentationsexperimente zeigen, dass Enameloid etwa sechsmal härter ist als Dentin. Die Härte von Haifischzähnen (Fluorapatit) und humanen Zähnen (Hydroxylapatit) ist vergleichbar, obwohl Fluorapatit als reines Mineral härter ist als Hydroxylapatit. Im Gegensatz zu rezenten Haifischzähnen haben Dentin und Enameloid von fossilen Haifischzähnen eine vergleichbare chemische Zusammensetzung (Fluorapatit). Die Enameloid-Mikrostruktur der fossilen Haifischzähne ist sehr gut erhalten und vergleichbar mit der in rezenten Haifischzähnen. Im Dentin fossiler Haifischzähne sind mittels Rasterelektronenmikroskopie mineralische Substanzen zu erkennen, die im Dentin rezenter Zähne nicht vorhanden sind. Dies könnte auf einen Rekristallisationsprozess während der Diagenese zurückzuführen sein. Krokodilzähne bestehen aus einem nanokristallinen Hydroxylapatit. Rasterelektronenmikroskopische Aufnahmen zeigen, dass die Enamelschicht verglichen mit humanen Zähnen und Haifischzähnen sehr dünn ist (100-200 μm). Die Kristallite im Enamel sind alle senkrecht zur Zahnoberfläche angeordnet, wobei es keine definierten Kristallitbündel gibt. Durch Thermogravimetrie und Synchrotron-Mikrocomputertomographie wurde ermittelt, dass Enamel den größten Mineralanteil besitzt, gefolgt von Dentin und dem Wurzelzement. Enameloid rezenter Haifischzähne wurde als Modellsystem für die Entwicklung biomimetischer Dentalkomposite ausgewählt, weil es, im Vergleich zu Hydroxylapatit, aus dem säureresistenteren Fluorapatit besteht. Zudem kann Fluorapatit synthetisch gut in unterschiedlichen Kristallit-Morphologien dargestellt werden. Zur Darstellung von biomimetischen Kompositen wurde Fluorapatit in unterschiedlichen Kristallit-Morphologien und -Größen hydrothermal synthetisiert. Kombiniert wurden diese Kristallite mit verschiedenen Methacrylat-Monomeren. Die Komposite wurden entweder durch Ultrazentrifugation des Fluorapatits in einer flüssigen Comonomermischung basierend auf Methylmethacrylat und anschließender thermisch initiierter Polymerisation mit Dibenzoylperoxid als Radikalstarter dargestellt, oder durch eine Polymerisation während der Ultrazentrifugation bei Raumtemperatur mit dem Zusatz eines tertiären Amins. Rasterelektronenmikroskopische Aufnahmen zeigen, dass ein kompaktes Material vorzugweise mit dem Amin-Zusatz erhalten wurde. Die Vickers-Härte der Komposite ist höher (0,3-0,4 GPa) als die der reinen Polymermatrix (0,2 GPa), wobei Haifischzähne noch härter sind (Dentin: 0,5-0,7 GPa; Enameloid: 3-4 GPa). Thermogravimetrische Analysen zeigen, dass der Mineralanteil der synthetischen Komposite bei ca. 60-70 Gew% liegt. Mattierungsdispersionen wurden auf Basis von Titandioxid (Anatas) und Stärkekleister bzw. Polyvinylpyrrolidon als Haftmittel entwickelt. Ein dichter Mattierungsfilm auf unterschiedlichen dentalen Materialoberflächen wurde mittels Rasterelektronenmikroskopie gezeigt. Analysen des getrockneten Mattierungsfilms mit Thermogravimetrie und energiedispersiver Röntgen-spektroskopie zeigen, dass der organische Anteil mit Polyvinylpyrrolidon als Haftmittel höher ist als bei der Verwendung von Stärkekleister. Erste klinische Analysen mit einer 3D-Kamera zeigen, dass geeignete Modelle erzeugt werden konnten. Zur Konservierung der Mattierungsdispersionen eignet sich Chlorhexidin, das bereits kommerziell in vielen antiseptischen Mundspülungen verwendet wird. Zusammenfassend behandelt die vorliegende Arbeit zwei Aspekte der modernen zahnmedizinischen Materialforschung. Ein Thema war die Charakterisierung von natürlichen Modellsystemen, d.h. Haifisch- und Krokodilzähnen, mit verschiedenen Analysemethoden. Die daraus resultierenden Ergebnisse können genutzt werden, um innovative und biomimetische Zahnersatzmaterialien zu entwickeln. Zudem wurden Mattierungsdispersionen dargestellt, die die Grundlage für moderne 3D-Abbildungstechniken sind. Dies kann dazu genutzt werden, um schnelle und exakte Zahnabdrücke zu erhalten.The aim of this study was the development of synthetic biomimetic fluoroapatite/polymer-composites, designed for their application as tooth restoration material. Additionally, dulling liquids for digital imaging of teeth were developed. Shark teeth and crocodile teeth were chosen as model systems, and thoroughly analyzed with various analytical methods. The outer layer of recent shark teeth (enameloid) consists of fluoroapatite, Ca5(PO4)3F, with a fluoride content of 3.1 wt%, which is nearly as high as in geological fluoroapatite crystals (3.64 wt%). The enameloid layer shows a higher crystallinity of the mineral phase compared to dentin. Enameloid consists of thin (50-80 nm) and long (> 1 μm) crystallites of fluoroapatite which are hierarchically organized in bundles. Three types of bundles with different orientations are present within the enameloid: circumferential, radial and axial crystallite bundles. Each crystallite bundle, regardless of its orientation, is covered by a thin layer of organic matrix. The outermost layer of the enameloid consists of the so-called "shiny layer", which is composed of randomly oriented solid polyhedral crystallites. Although there is a strong structural anisotropy within the enameloid, the local mechanical properties are widely isotropic. Vickers microhardness tests and nanoindentation experiments indicated that enameloid is about six times harder than dentin. The hardness of shark teeth (fluoroapatite) and human teeth (hydroxyapatite) is comparable, although, as pure mineral, fluoroapatite is harder than hydroxyapatite. In contrast to recent shark teeth, enameloid and dentin of fossilized shark teeth show similar chemical compositions, i.e., nearly stoichiometric fluoroapatite. The enameloid microstructure of fossilized shark teeth has been well preserved and is comparable to the microstructure of recent shark teeth. Scanning electron micrographs of dentin of fossilized shark teeth showed that mineral substances are present, which may be due to recrystallization processes during diagenesis. Crocodile teeth consist of nanocrystalline hydroxyapatite. Scanning electron micrographs showed that the enamel layer is very thin (100-200 μm), in contrast to thicker layers founds in human and shark teeth. The crystallites of the enameloid are oriented perpendicularly to the tooth surface, and no defined crystallite bundles can be observed. Enamel has the highest mineral content, followed by dentin and cementum as shown by thermogravimetry and synchrotron microcomputer tomography. Shark tooth enameloid was selected as a model system for the development of biomimetic dental composites because it consists of fluoroapatite which has a higher acid stability than hydroxyapatite. Additionally, fluoroapatite can be readily synthesized in various crystallite morphologies. For the preparation of biomimetic composites, fluoroapatite was hydrothermally synthesized in different crystallite morphologies and sizes. The crystallites were combined with different methacrylate monomers. The composites were then prepared using either of two routines. Firstly, through ultracentrifugation of fluoroapatite in a liquid comonomer mixture (based on methyl methacrylate), followed by a thermally initiated polymerization using dibenzoyl peroxide as a radical initiator. Alternatively, composites were synthesized via polymerization during ultracentrifugation at room temperature, with the second routine, utilizing the addition of a tertiary amine. Scanning electron micrographs showed that a compact material was achieved more effectively with the second routine, utilizing the addition of a tertiary amine. The composites showed higher Vickers hardness values (0.3-0.4 GPa) compared to the pure polymer matrix (0.2 GPa), whereas shark teeth are even harder (dentin: 0.5-0.7 GPa; enameloid: 3-4 GPa). The mineral content of the synthetic composites was 60-70 wt% as determined by thermogravimetry. Dulling liquids based on titanium dioxide (anatase) and a starch paste or polyvinylpyrrolidone were prepared. The resulting matting films densely covered different dental materials as shown by scanning electron microscopy. Furthermore, the dried matting films were analyzed by thermogravimetry and energy dispersive X-ray spectroscopy. In matting films which contained polyvinylpyrrolidone as adhesive the organic content is higher than with adhesives based on starch paste. First clinical analyses using 3D imaging showed that suitable models could be produced. Additionally, chlorhexidine can be used as a preservative because it is already found in commercially produced antiseptic mouthwashes. This work has covered two important aspects of modern dental material science: First, a thorough analysis of natural model systems (i.e., shark teeth and crocodile teeth) can foster research for innovative dental materials with improved durability and stability. Second, efficient matting films which are a prerequisite for modern, computer-based 3D imaging were developed. This can be used to obtain faster and more exact dental impressions

Comparative 3D analyses and palaeoecology of giant early amphibians (Temnospondyli: Stereospondyli)

Macroevolutionary, palaeoecological and biomechanical analyses in deep time offer the possibility to decipher the structural constraints, ecomorphological patterns and evolutionary history of extinct groups. Here, 3D comparative biomechanical analyses of the extinct giant early amphibian group of stereospondyls together with living lissamphibians and crocodiles, shows that: i) stereospondyls had peculiar palaeoecological niches with proper bites and stress patterns very different than those of giant salamanders and crocodiles; ii) their extinction may be correlated with the appearance of neosuchians, which display morphofunctional innovations. Stereospondyls weathered the end-Permian mass extinction, re-radiated, acquired gigantic sizes and dominated (semi) aquatic ecosystems during the Triassic. Because these ecosystems are today occupied by crocodilians, and stereospondyls are extinct amphibians, their palaeobiology is a matter of an intensive debate: stereospondyls were a priori compared with putative living analogous such as giant salamanders and/or crocodilians and our new results try to close this debate.Peer ReviewedPostprint (published version

The role of fatigue in patients with complex regional pain syndrome.

BACKGROUND AND PURPOSE Fatigue affects patients across a variety of neurological diseases, including chronic pain syndromes such as complex regional pain syndrome (CRPS). In CRPS, fatigue is often underestimated, as the focus lies in the assessment and managing of pain and sensorimotor deficits. This study aimed to investigate the prevalence, characteristics, and influence of fatigue on CRPS severity and quality of life in these patients. Such insights could enhance the clinical management of this challenging condition. METHODS In this prospective study, 181 CRPS patients and 141 age and gender-matched individuals with injury but without chronic pain were interviewed using the Fatigue Scale for Motor and Cognitive Function to assess fatigue. Depressive symptoms and quality of life (QoL) were also evaluated as additional outcome measures. Statistical analysis was performed to examine differences in fatigue prevalence between the groups, as well as associations with CRPS severity, pain levels, and clinical phenotype. In addition, best subsets regression was used to identify the primary factors influencing QoL. Fatigue was tested in a mediation analysis as a mediator between pain and depression. RESULTS CRPS patients showed significantly higher fatigue levels compared to controls (CRPS: 75 [IQR: 57-85] vs. controls: 39 [IQR: 25-57]). Based on the FSMC, 44.2% in the control group experienced fatigue, while 85% of patients with CRPS experienced fatigue (p < 0.001), of which 6% were mild, 15% moderate, and 67% severe. In CRPS severe fatigue was associated with higher pain intensities compared to no fatigue (pain at rest: p = 0.003; pain during movement: p = 0.007) or moderate fatigue (pain during movement: p = 0.03). QoL in our cohort was mainly influenced by pain (pain during movement: adj.R2 = 0.38; p < 0.001, pain at rest: Δadj.R2 = 0.02, p = 0.007) and depressive symptoms (Δadj.R2 = 0.12, p < 0.001). Subsequent analyses indicated that pain and depressive symptoms primarily impact QoL in CPRS whereas fatigue may exert an indirect influence by mediating the connection between pain and depression (p < 0.001). CONCLUSIONS This pioneering study investigates the prevalence of fatigue in CRPS patients and its relation to disease characteristics. Our results indicate a high prevalence of severe fatigue, strongly correlated with pain intensity, and its importance in the interaction between pain and depression in CRPS. These findings underscore the significant role of fatigue as a disease factor in CRPS. Therefore, the evaluation of CRPS-related disability should include a standardized assessment of fatigue for comprehensive clinical management

Quantitative muscle MRI in sporadic inclusion body myositis (sIBM): A prospective cohort study

Background: Sporadic inclusion body myositis (sIBM) is the predominant idiopathic inflammatory myopathy (IIM) in older people. Limitations of classical clinical assessments have been discussed as possible explanations for failed clinical trials, underlining the need for more sensitive outcome measures. Quantitative muscle MRI (qMRI) is a promising candidate for evaluating and monitoring sIBM. Objective: Longitudinal assessment of qMRI in sIBM patients. Methods: We evaluated fifteen lower extremity muscles of 12 sIBM patients (5 females, mean age 69.6, BMI 27.8) and 12 healthy age-and gender-matched controls. Seven patients and matched controls underwent a follow-up evaluation after one year. Clinical assessment included testing for muscle strength with Quick Motor Function Measure (QMFM), IBM functional rating scale (IBM-FRS), and gait analysis (6-minute walking distance). 3T-MRI scans of the lower extremities were performed, including a Dixon-based sequence, T2 mapping and Diffusion Tensor Imaging. The qMRI-values fat-fraction (FF), water T2 relaxation time (wT2), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (RD) were analysed. Results: Compared to healthy controls, significant differences for all qMRI parameters averaged over all muscles were found in sIBM using a MANOVA (p < 0.001). In low-fat muscles (FF < 10%), a significant increase of wT2 and FA with an accompanying decrease of MD, λ1, and RD was observed (p≤0.020). The highest correlation with clinical assessments was found for wT2 values in thigh muscles (r≤-0.634). Significant changes of FF (+3.0%), wT2 (+0.6 ms), MD (-0.04 10-3mm2/s), λ1 (-0.05 10-3mm2/s), and RD (-0.03 10-3mm2/s) were observed in the longitudinal evaluation of sIBM patients (p≤0.001). FA showed no significant change (p = 0.242). Conclusion: qMRI metrics correlate with clinical findings and can reflect different ongoing pathophysiological mechanisms. While wT2 is an emerging marker of disease activity, the role of diffusion metrics, possibly reflecting changes in fibre size and intracellular deposits, remains subject to further investigations

The composition of the dental pellicle: an updated literature review

BackgroundThe dental pellicle is a thin layer of up to several hundred nm in thickness, covering the tooth surface. It is known to protect the teeth from acid attacks through its selective permeability and it is involved in the remineralization process of the teeth. It functions also as binding site and source of nutrients for bacteria and conditioning biofilm (foundation) for dental plaque formation.MethodsFor this updated literature review, the PubMed database was searched for the dental pellicle and its composition.ResultsThe dental pellicle has been analyzed in the past years with various state-of-the art analytic techniques such as high-resolution microscopic techniques (e.g., scanning electron microscopy, atomic force microscopy), spectrophotometry, mass spectrometry, affinity chromatography, enzyme-linked immunosorbent assays (ELISA), and blotting-techniques (e.g., western blot). It consists of several different amino acids, proteins, and proteolytic protein fragments. Some studies also investigated other compounds of the pellicle, mainly fatty acids, and carbohydrates.ConclusionsThe dental pellicle is composed mainly of different proteins, but also fatty acids, and carbohydrates. Analysis with state-of-the-art analytical techniques have uncovered mainly acidic proline-rich proteins, amylase, cystatin, immunoglobulins, lysozyme, and mucins as main proteins of the dental pellicle. The pellicle has protective properties for the teeth. Further research is necessary to gain more knowledge about the role of the pellicle in the tooth remineralization process

Ca2+ release and buffering effects of synthetic hydroxyapatite following bacterial acid challenge

Background Synthetic particulate hydroxyapatite (HAP; Ca-5(PO4)(3)(OH)) is used as ingredient in oral care products but its effects on cariogenic biofilms are not clear yet. The primary mode of action of HAP may be acting as a calcium phosphate reservoir when deposited in oral biofilms and release Ca2+ and (hydrogen) phosphate ions upon bacterial acid challenge. The aim of this in vitro study was to test this hypothesis by investigating release of Ca2+ ions and potential buffering effects from HAP upon bacterial acid challenge in planktonic cultures and biofilms of Streptococcus mutans. Methods Planktonic cultures of S. mutans were grown in BHI broth with 1% sucrose or with additional 5% HAP or 5% silica for up to 48 h. Separately, biofilms of S. mutans were grown in BHI for 72 h in total. After 24 h of this biofilm culture, either BHI alone or BHI with additional 0.5% HAP or 0.5% silica was added. After 48 h, BHI with 1% sucrose was added to allow bacterial acid formation. Ca2+ release was determined colorimetrically and pH measurements were performed using a pH electrode. For statistical analysis, non-parametrical procedures were applied (n >= 10; Mann-Whitney U test; alpha = 0.05). Results Relevant release of Ca2+ was only evident in planktonic cultures or biofilms with HAP but not in both other groups (p <= 0.001). In suspended biofilms with HAP, median pH was 4.77 after 72 h and about 0.5 pH units higher as compared to both other groups (4.28 or 4.32, respectively; p <= 0.001). Conclusions Under the tested conditions, synthetic HAP releases Ca2+ ions upon bacterial acid challenge and may also show some buffering capacity but further studies are needed to investigate whether the concentrations tested here can also be reached clinically in dental biofilms

Evaluation of Neuromuscular Diseases and Complaints by Quantitative Muscle MRI

Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle muscular dystrophy), inflammatory (inclusion body myositis), and metabolic myopathy (Pompe disease) as well as patients with post-COVID-19 conditions suffering from myalgia to healthy controls. Methods: Ten subjects of each group underwent a 3T lower extremity muscle MRI, including a multi-echo, gradient-echo, Dixon-based sequence, a multi-echo, spin-echo (MESE) T2 mapping sequence, and a spin-echo EPI diffusion-weighted sequence. Furthermore, the following clinical assessments were performed: Quick Motor Function Measure, patient questionnaires for daily life activities, and 6-min walking distance. Results: Different involvement patterns of conspicuous qMRI parameters for different NMDs were observed. qMRI metrics correlated significantly with clinical assessments. Conclusions: qMRI metrics are suitable for evaluating patients with NMD since they show differences in muscular involvement in different NMDs and correlate with clinical assessments. Still, standardisation of acquisition and processing is needed for broad clinical use

Pre- and post-skeletal muscle biopsy quantitative magnetic resonance imaging reveals correlations with histopathological findings

Background and purpose: Quantitative muscle magnetic resonance imaging (MRI) is a promising non-invasive method in the diagnostic workup as well as follow-up of neuromuscular disorders. The aim of this study was to correlate quantitative MRI (qMRI) parameters to histopathological changes in skeletal muscle tissue and thus to verify the data from our pilot study. Methods: Twenty-six patients (eight females, 46.4 ± 15.1 years) were examined within 72 h before and within 24 h after a skeletal muscle biopsy using quantitative muscle MRI. Post-biopsy MRI was employed to pinpoint the exact localization of the biopsy. qMRI parameters including fat fraction, water T2 relaxation time and diffusion metrics including fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were extracted from the localization of the biopsy and correlated with histopathological findings. Additionally, three different segmentation masks were applied to the qMRI dataset, to evaluate whether the whole muscle represents the exact biopsy location. Results: Fat fraction and water T2 relaxation time in qMRI correlated significantly with the fat fraction in the muscle biopsy and histopathological inflammatory markers. Fractional anisotropy correlated with the quantity of type 2 fibres, whilst mean diffusivity correlated with p62. No differences were found using different segmentation masks in qMRI. Conclusions: In this follow-up study, the results from our previous study were verified regarding the correlation of qMRI parameters with histopathological features in muscle biopsies, indicating that qMRI serves as a suitable non-invasive method in the follow-up of patients with neuromuscular disorders. If post-biopsy MRI is not available, whole muscle volume can be used for histopathological correlations

Joint European Academy of Neurology–European Pain Federation–Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment

Background and Purpose: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). Methods: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. Results: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. Conclusions: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed