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Abstract Introduction This pilot study investigated the effects of a 12-week administration of a nutritional supplement containing special collagen peptides on the structural and molecular properties of the collagen fiber network in the human skin. For the assessments, the suction blister method and electron microscopical comparisons were used. Methods Three suction blisters were generated on the inner forearm of each test subject before and after the 12-week administration of the nutritional supplement. High-resolution scanning electron microscopy (SEM) was employed to meticulously investigate the structural characteristics of the skin’s collagen network, including the length and diameter of collagen fibers within the suction blister roof. Furthermore, the analysis included immunohistochemistry and fluorescence light microscopy to study hyaluronic acid within the extracellular matrix. Additional assessments encompassed changes in various epidermal parameters. Nine female participants within the age range of 43.7–61.8 years (mean: 52.5 ± 5.9 years) completed the study in accordance with the study protocol. Results Compared with baseline, the 12-week supplementation regimen led to a statistically significant average increase in the collagen fiber network size of 34.56% (p

IntroductionThe HGSHS:A is one of the most commonly used measures of hypnotic suggestibility. However, this test suffers from low feasibility due to a time requirement exceeding 1 h, and from a questionable representation of the normal population. Recently, a short version of HGSHS-5:G was developed and published, and now the first results are available. The scope of this investigation was to verify the assumption of equally positioned and normally distributed scores, resulting in equally sized suggestibility groups in a number of different studies with full or short versions of HGSHS, and to compare the results of the 11-item score with the 5-item score, the latter being calculated from either the full version or the short version test.MethodsData from 21 studies with testing for HGSHS were analyzed, 15 using the HGSHS:A full version and six using the HGSHS-5:G short version, for a total of 2,529 data sets. Position and distribution of both the 11-item score and the 5-item score were tested. Linear regression analysis was used to compare the two scores, as well as cross-table and weighted Cohen’s kappa to determine the match of grouping into low and high suggestibility. To evaluate contributing factors to the observed differences in the study results, a multifactorial analysis of variance was performed.ResultsIn the different studies, position and distribution of scores, as well as group sizes for low and high suggestibles, varied. All score distributions were found to be non-normal and shifted to the right from the middle score; the shift was more extensive with the 11-item score. The correlation between both scores calculated from full version tests was moderate (R2 = 0.69), as was the match of suggestibility grouping (κ = 0.58). Studies using the short version involving less student-dominated populations showed sufficient agreement with the full version, but lower scores were caused by an increase in the zero score.ConclusionA normal population is not represented in most applications of HGSHS, and grouping into low and high suggestibles varies, mainly due to different positions of score distributions. A direct comparison of full and short versions of HGSHS tested in the same subjects is still missing.

Aspects of hypnosis and its application in psychotherapy, psychosomatics and medicine are examined and contextualized in the 250-year history of hypnosis. Imagination as an essential element of hypnotic treatments appeared as early as 1784 as an argument rejecting the theory of animal magnetism of Franz Anton Mesmer. In somnambulism of German romanticism, another proto-form of hypnosis after 1800, concepts of the mind–body problem were dealt with, which still characterize the understanding of unconscious mental processes today. Hypnosis was at the beginning of psychoanalysis, but was not pursued further by Sigmund Freud from 1900 onwards. Nevertheless, there were some hypnoanalytical approaches in the 20th century, as well as attempts to integrate hypnosis into behavior therapy. Techniques of imagination and relaxation combine both; in particular findings from cognitive psychology explain processes of both hypnosis and cognitive behavioral therapy. The influence of social psychology brought a new perspective to the debate about the nature of hypnosis, which continues to this day: is hypnosis to be understood as a special state of consciousness or is it a completely normal, mundane interaction? The experiments that were carried out to support one side or the other were also dependent on the hypnotizability of the subjects involved, as the more difficult hypnotic phenomena such as paralysis, hallucinations or identity delusions can only be demonstrated by highly hypnotizable subjects. The fact that these are not mere compliance reactions has now been proven by many studies using imaging techniques. But even those who are moderately hypnotizable benefit from hypnosis rituals. Variables postulated by socio-cognitive hypnosis researchers, such as motivation and expectation, are relevant, as is a good “hypnotic rapport.” Practical application of hypnotherapy today is characterized by the innovative techniques and strategies developed by Milton H. Erickson. Research into the effectiveness of hypnosis in the field of psychotherapy and psychosomatics still leaves much to be done. The situation is different in the field of medical hypnosis, where there are considerably more studies with a satisfactory design and verifiable effects. However, the impact in practical application in everyday medical practice is still low. Newer developments such as virtual reality and artificial intelligence are being looked at with critical interest.

Abstract Argumentation is crucial to fostering scientific reasoning and problem-solving in science education. However, researchers and teachers still report problems facilitating argumentation in the classroom. This may be influenced by the design of the corresponding professional development programs (PDPs) and the focus of the underlying research. To describe the state of the research regarding science teacher PDPs on facilitating argumentation, we systematically reviewed publications from the last 20 years in terms of their design, with selected low- and high-inference characteristics, for example, in terms of the addressed professional competence and the argumentation framework. The results illustrate a broad spectrum of teacher PDPs on argumentation in terms of formal-structural aspects (e.g., sample size) and interests (e.g., methodology). We found, for example, that pre-service teachers’ argumentation PDPs are less frequent than in-service teachers’ argumentation PDPs and that research rarely focuses on situation-specific competencies, such as professional vision or decision-making. Additionally, we report challenges in analyzing the argumentation framework and discuss possible reasons for this. We critically evaluate these and other findings, point to fruitful directions for further research and reviews, and inform practitioners of professional development of argumentation.

Abstract The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior.

Abstract In this proof-of-concept study, we questioned whether the influence of TMS on cortical excitability can be applied to classical conditioning. More specifically, we investigated whether the faciliatory influence of paired-pulse TMS on the excitability of the human motor cortex can be transferred to a simultaneously presented auditory stimulus through conditioning. During the conditioning phase, 75 healthy young participants received 170 faciliatory paired TMS pulses (1st pulse at 95% resting motor threshold, 2nd at 130%, interstimulus interval 12 ms), always presented simultaneously with one out of two acoustic stimuli. In the test phase, 20 min later, we pseudorandomly applied 100 single TMS pulses (at 130% MT), 50 paired with the conditioned tone—50 paired with a control tone. Using the Wilcoxon-Signed Rank test, we found significantly enhanced median amplitudes of motor evoked potentials (MEPs) paired with the conditioned tone as compared to the control tone, suggesting successful conditioning (p = 0.031, responder rate 55%, small effect size of r = − 0.248). The same comparison in only those participants with a paired-pulse amplitude

Humans and other animals can maintain constant payoffs in an uncertain environment by steadily re-evaluating and flexibly adjusting current strategy, which largely depends on the interactions between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). While the ventromedial PFC (vmPFC) represents the level of uncertainty (i.e., prior belief about external states), it remains unclear how the brain recruits the PFC-MD network to re-evaluate decision strategy based on the uncertainty. Here, we leverage non-linear dynamic causal modeling on fMRI data to test how prior belief-dependent activity in vmPFC gates the information flow in the PFC-MD network when individuals switch their decision strategy. We show that the prior belief-related responses in vmPFC had a modulatory influence on the connections from dorsolateral PFC (dlPFC) to both, lateral orbitofrontal (lOFC) and MD. Bayesian parameter averaging revealed that only the connection from the dlPFC to lOFC surpassed the significant threshold, which indicates that the weaker the prior belief, the less was the inhibitory influence of the vmPFC on the strength of effective connections from dlPFC to lOFC. These findings suggest that the vmPFC acts as a gatekeeper for the recruitment of processing resources to re-evaluate the decision strategy in situations of high uncertainty.

The effects of spurious modes on the performance of microwave systems is studied using a Monte Carlo algorithm based on randomized mode mixtures. A high power microwave launcher for the heating of fusion plasmas is used as an example, but the method can be applied to arbitrary linear optical systems. The linearity allows to simulate the beam propagation only for the pure modes while the actual Monte Carlo analysis is done using linear combinations of these fundamental solutions. This significantly decreases the calculation time. The results are histograms for truncation losses on mirrors, peak power densities and the overall efficiency. These results allow the definition of safety margins when designing high power millimeter wave components. In addition, a worst-case prediction for reduction of the overall efficiency due to spurious modes can be confirmed by the Monte Carlo analysis.

Social semiotic discussions about the role played by representations in effective teaching and learning in areas such as physics have led to theoretical proposals that have a strong common thread: in order to acquire an appropriate understanding of a particular object of learning, access to the disciplinary relevance aspects in the representations used calls for the attainment of representational competence across a particular critical constellation of systematically used semiotic resources (which are referred to as modes, see more on this later). However, an affirming empirical investigation into the relationship between a particular object of learning and different representational formulations, particularly with large numbers of students, is missing in the literature, especially in the context of university-level physics education. To start to address, this research shortfall the positioning for this article is that such studies need to embrace the complexities of student thinking and application of knowledge. To achieve this, both factor and network analyses were used. Even though both approaches are grounded in different frameworks, for the task at hand, both approaches are useful for analyzing clustering dynamics within the responses of a large number of participants. Both also facilitate an exploration of how such clusters may relate to the semiotic resource formulation of a representation. The data were obtained from a questionnaire given to 1368 students drawn from 12 universities across 7 countries. The questionnaire deals with the refraction of light in introductory-level physics and involves asking students to give their best prediction of the relative visual positioning of images and objects in different semiotically constituted situations. The results of both approaches revealed no one-to-one relationship between a particular representational formulation and a particular cluster of student responses. The factor analysis used correct answer responses to reveal clusters that brought to the fore three different complexity levels in relation to representation formulation. The network analysis used all responses (correct and incorrect) to reveal three structural patterns. What is evident from the results of both analyses is that they confirm two broad conclusions that have emerged from social semiotic explorations dealing with representations in relation to attempting to optimize teaching and learning. The first, which is linked to a facilitating-awareness perspective, is that any given disciplinary visual representation can be expected to evoke a dispersed set of knowledge structures, which is referred to as their relevance structure. Thus, the network analysis results can be seen as presenting a unique starting point for studies aiming to identify such relevance structure. The second broad conclusion is that disciplinary visual representation can and often does contain more disciplinary-relevant aspects than what may be directly visible in a given representation. These are referred to as the appresent aspects that need to become part of the total awareness needed by someone to constitute an intended meaning. The results of the factor analysis can then also be seen to be a way of capturing all the disciplinary-relevant aspects (both present and appresent). Educational implications are discussed.

Abstract Background Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. Methods We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. Results Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p

Students at all levels of education experience difficulties with the concepts of measurement uncertainties. One task that includes concepts of measurement uncertainties is a data comparison problem where students decide whether two datasets are in agreement or not—an authentic scientific practice. To aid students with these concepts and tasks, sensitive instruments are needed that probe students’ understanding and track their progress. We present a tool in the form of a coding manual that analyzes students’ written justifications for such a data comparison problem. With this coding manual, justifications are coded based on the quantity that is compared and the deciding criterion in this comparison. Our coding manual was used in the evaluation of a digital learning environment (DLE). In this evaluation, 154 participants (aged 14–17 years) wrote a justification for a data comparison problem before and after going through the DLE. These participants were randomly assigned to one of three groups where each group was taught an increased amount of concepts regarding measurement uncertainties. By analyzing the participants’ justifications with our coding manual, we could probe their ability to compare datasets on a fine-grained level. The sensitivity of our tool was illustrated by the increase in higher quality codes with the increased conceptual teaching between the three groups. We argue that our tool for coding justifications can be applied to any data comparison problem giving detailed information about what data analysis methods students use and how they reach their conclusion and thus contributes to the research on students’ understanding of measurement uncertainties.

Abstract Introduction Nutrition claims are one of the most common tools used to improve food decisions. Previous research has shown that nutrition claims impact expectations; however, their effects on perceived pleasantness, valuation, and their neural correlates are not well understood. These claims may have both intended and unintended effects on food perception and valuation, which may compromise their effect on food decisions. Methods We investigated the effects of nutrition claims on expectations, perceptions, and valuation of milk‐mix drinks in a behavioral (n = 110) and an fMRI (n = 39) study. In the behavioral study, we assessed the effects of a “fat‐reduced” and a “protein‐rich” nutrition claim on expected and perceived food attributes of otherwise equal food products. In the fMRI study, we investigated the effect of a “protein‐rich” claim on taste pleasantness perception and valuation, and on their neural correlates during tasting and swallowing. Results We found that both nutrition claims increased expected and perceived healthiness and decreased expected but not perceived taste pleasantness. The “protein‐rich” claim increased expected but not perceived satiating quality ratings, while the “fat‐reduced” claim decreased both expected and perceived satiating quality ratings. In the absence vs. presence of the “protein‐rich” claim, we observed an increased activity in a cluster extending to the left nucleus accumbens during tasting and an increased functional connectivity between this cluster and a cluster in right middle frontal gyrus during swallowing. Conclusion Altogether, we found that nutrition claims impacted expectations and attenuated reward‐related responses during tasting but did not negatively affect perceived pleasantness. Our findings support highlighting the presence of nutrients with positive associations and exposure to foods with nutrition claims to increase their acceptance. Our study offers insights that may be valuable in designing and optimizing the use of nutrition claims.

Interactions across frontal cortex are critical for cognition. Animal studies suggest a role for mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human decision making are unclear. Here, inspired by animal work, we extended a neural model of an executive frontal-MD network and trained it on a human decision-making task for which neuroimaging data were collected. Using a biologically-plausible learning rule, we found that the model MD thalamus compressed its cortical inputs (dorsolateral prefrontal cortex, dlPFC) underlying stimulus-response representations. Through direct feedback to dlPFC, this thalamic operation efficiently partitioned cortical activity patterns and enhanced task switching across different contingencies. To account for interactions with other frontal regions, we expanded the model to compute higher-order strategy signals outside dlPFC, and found that the MD offered a more efficient route for such signals to switch dlPFC activity patterns. Human fMRI data provided evidence that the MD engaged in feedback to dlPFC, and had a role in routing orbitofrontal cortex inputs when subjects switched behavioral strategy. Collectively, our findings contribute to the emerging evidence for thalamic regulation of frontal interactions in the human brain.

Several publications with healthcare professionals, such as psychotherapists, have shown a significant difference in personality styles in practitioners using hypnosis compared to those not using hypnosis. To investigate differences in personality styles, dentists were contacted to participate in a personality-inventory [Personality Style and Disorder Inventory (PSDI)] online survey. Dentists using hypnosis (HYP DGZH) (n = 418) were compared to dentists not using hypnosis (NONHYP DENT) (n = 162). Results show that hypnosis-practicing dentists score significantly higher in the intuitive/schizotypal ST personality style (p < 0.001) compared to non-hypnosis-practicing dentists. Female dentists scored significantly higher in intuitive/schizotypal ST and unselfish/self-sacrificing SL in the HYP DGZH sample but only in unselfish/self-sacrificing SL in the NONHYP DENT sample. The percentage of women was similar in both samples (68.2%; 67.3%). Intuitive/schizotypal ST was found to be the predominant personality style of men who are interested in or use hypnosis, metaphorically so-called “homo hypnoticus.” Within the limitations of this cross-sectional non-interventional observational online-questionnaire study, results expand this notion to the so-called “homo hypnoticus dentalis.” However, further research on the subject is needed to investigate and confirm this personality type in other than the German-speaking DACH countries.

The Late Jurassic elasmobranch Protospinax annectans is often regarded as a key species to our understanding of crown group elasmobranch interrelationships and the evolutionary history of this group. However, since its first description more than 100 years ago, its phylogenetic position within the Elasmobranchii (sharks and rays) has proven controversial, and a closer relationship between Protospinax and each of the posited superorders (Batomorphii, Squalomorphii, and Galeomorphii) has been proposed over the time. Here we revise this controversial taxon based on new holomorphic specimens from the Late Jurassic Konservat-Lagerstätte of the Solnhofen Archipelago in Bavaria (Germany) and review its skeletal morphology, systematics, and phylogenetic interrelationships. A data matrix with 224 morphological characters was compiled and analyzed under a molecular backbone constraint. Our results indicate a close relationship between Protospinax, angel sharks (Squatiniformes), and saw sharks (Pristiophoriformes). However, the revision of our morphological data matrix within a molecular framework highlights the lack of morphological characters defining certain groups, especially sharks of the order Squaliformes, hampering the phylogenetic resolution of Protospinax annectans with certainty. Furthermore, the monophyly of modern sharks retrieved by molecular studies is only weakly supported by morphological data, stressing the need for more characters to align morphological and molecular studies in the future.

This study contributes to the therapist variable in general and the personality profile of securely and insecurely attached psychotherapists and other healthcare professionals in particular. In a preceding study, it has been found that insecurely attached psychotherapists differ in nine personality styles from securely attached ones. The aim of the present study was to replicate these findings and to investigate whether they also apply to other health professions such as dentists. About 891 subjects from two German professional societies for hypnosis were surveyed online with a personality questionnaire [Personality Styles and Disorder Inventory (PSDI)] and an attachment questionnaire [Relationship Scale Questionnaire (RSQ)]. Since these subjects were interested in hypnosis and used it in their practice (HYP), 150 dentists without a hypnosis context (NONHYP) were studied as a control group with the same survey. The results of the preceding attachment study could be replicated: Insecurely attached healthcare professionals differed significantly from securely attached ones in the same nine (plus one, i.e., 10) personality styles if they use psychological methods including hypnosis. If they do not use psychological methods (like the NONHYP dentists), they differ in half of the personality styles. No within-sample and no between-sample differences have been found in the assertive/antisocial (AS) personality style. No within-sample differences have also been found in the conscientious/compulsive (ZW) and the intuitive/schizotypal (ST) personality styles. However, large between-sample differences were obvious in ZW and the ST. Both of the samples of the dentist were much more compulsive than the two psychotherapeutic samples. In addition, both of the HYP samples were much more schizotypal than the NONHYP samples. The latter is the general signature of those individuals who are interested in hypnosis and were metaphorically termed homo hypnoticus. It seems that AS, ZW, and ST are independent of attachment.

Sporadic late-onset Alzheimer's disease (AD) is the most frequent cause of dementia associated with aging. Due to the progressive aging of the population, AD is becoming a healthcare burden of unprecedented proportions. Twenty years ago, it was reported that some indole molecules produced by the gut microbiota possess essential biological activities, including neuroprotection and antioxidant properties. Since then, research has cemented additional characteristics of these substances, including anti-inflammatory, immunoregulatory, and amyloid anti-aggregation features. Herein, we summarize the evidence supporting an integrated hypothesis that some of these substances can influence the age of onset and progression of AD and are central to the symbiotic relationship between intestinal microbes and the brain. Studies have shown that some of these substances' activities result from interactions with biologically conserved pathways and with genetic risk factors for AD. By targeting multiple pathologic mechanisms simultaneously, certain indoles may be excellent candidates to ameliorate neurodegeneration. We propose that management of the microbiota to induce a higher production of neuroprotective indoles (e.g., indole propionic acid) will promote brain health during aging. This area of research represents a new therapeutic paradigm that could add functional years of life to individuals who would otherwise develop dementia.

Early diagnosis and treatment of rheumatoid arthritis (RA) are of critical importance to halt the progression of the disease. Optimal use of advanced imaging techniques or biomarkers may facilitate early diagnosis of RA. Even though many disease-modifying anti-rheumatic drugs (DMARDs) are available for RA treatment, biological DMARDs (bDMARDs) offer expanding therapeutic options and good outcomes in patients with RA who do not have a sufficient response to conventional synthetic DMARDs. However, high costs of bDMARDs have limited patient access to optimised disease management and increased the cost burden for healthcare systems. The advent of biosimilars led to significant cost savings driven by price competition among the reference products, which could be beneficial for healthcare systems. Healthcare provider (HCP)–patient communication and informed shared decision-making are crucial to prevent the occurrence of a nocebo effect, which results from negative perceptions that patients may have and could lead to less effective outcomes. Research has demonstrated that effective communication between HCPs and patients utilising positive framing can improve acceptance by patients to be initiated on or switched to a biosimilar and can help to integrate biosimilars into routine clinical practice to maximise benefits for patients with RA.

Abstract Introduction In 2016, SB4 (Benepali®) became the first etanercept (ETN) biosimilar to obtain marketing authorisation in Europe. Despite robust analytical and clinical comparisons, outstanding questions remain on SB4 use in routine practice. Methods A systematic search for publications on real-world evidence of SB4 effectiveness, safety and drug survival was undertaken using search terms (SB4 OR Benepali OR biosimilar etanercept OR innovator etanercept) in the BIOSIS® Toxicology, BIOSIS Previews®, Embase® and MEDLINE® databases up to 17 January 2019. Results Of 959 articles identified, eight journal articles, two journal letters and 23 congress abstracts were selected on criteria of original real-world evidence with a clinical focus. As expected with real-world evidence, quality scoring showed that the evidence had high external validity but lower internal validity. A total of 13,552 patients were described across nine European countries and all approved SB4 indications: 2499 were ETN-naïve and 11,053 switched from reference ETN to SB4 (switchers). Switch acceptance rates (a combination of clinicians offering and patients accepting initiation on SB4) ranged between 51.6% and 99.0%; patient support programmes positively contributed to acceptance. Disease activity was generally similar pre- and post-switch (typically 3-month timeframe). Retention rates across studies were at least 75% (up to 12 months follow-up). No new safety signals were identified. Differences in discontinuation rates versus historic controls reported in some studies may have been influenced by differences in treatment practices, lack of clinician confidence and nocebo effects. Conclusion Nearly 2500 ETN-naïve patients have been initiated on SB4 and outcomes are similar to those patients receiving reference ETN. Overall this systematic review of real-world evidence provides additional reassurance that SB4 is as effective and safe as reference ETN in both switched and naïve patients. Funding Biogen International GmbH.