Time-Dependent Prediction Models for Individual Prognosis of Chronic Postsurgical Pain following Knee Replacement Based on an Extensive Multivariable Data Set.

(1) Background: Clinically useful prediction models for chronic postsurgical pain (CPSP) in knee replacement (TKA) are lacking. (2) Methods: In our prospective, multicenter study, a wide-ranging set of 91 variables was collected from 933 TKA patients at eight time points up to one year after surgery. Based on this extensive data pool, simple and complex prediction models were calculated for the preoperative time point and for 6 months after surgery, using least absolute shrinkage and selection operator (LASSO) 1se and LASSO min, respectively. (3) Results: Using preoperative data only, LASSO 1se selected age, the Revised Life Orientation Test on pessimism, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-subscore pain and the Timed "Up and Go" Test for prediction, resulting in an area under the curve (AUC) of 0.617 and a Brier score of 0.201, expressing low predictive power only. Using data up to 6 months after surgery, LASSO 1se included preoperative Patient Health Questionnaire-4, Knee Injury and Osteoarthritis Outcome Score (KOOS)-subscore pain (pain) 3 months after surgery (month), WOMAC pain 3 and 6 months, KOOS subscore symptoms 6 months, KOOS subscore sport 6 months and KOOS subscore Quality of Life 6 months. This improved the predictive power to an intermediate one (AUC 0.755, Brier score 0.168). More complex models computed using LASSO min did little to further improve the strength of prediction. (4) Conclusions: Even using multiple variables and complex calculation methods, the possibility of individual prediction of CPSP after TKA remains limited.

Enhancing biomechanical machine learning with limited data: generating realistic synthetic posture data using generative artificial intelligence.

Objective: Biomechanical Machine Learning (ML) models, particularly deep-learning models, demonstrate the best performance when trained using extensive datasets. However, biomechanical data are frequently limited due to diverse challenges. Effective methods for augmenting data in developing ML models, specifically in the human posture domain, are scarce. Therefore, this study explored the feasibility of leveraging generative artificial intelligence (AI) to produce realistic synthetic posture data by utilizing three-dimensional posture data. Methods: Data were collected from 338 subjects through surface topography. A Variational Autoencoder (VAE) architecture was employed to generate and evaluate synthetic posture data, examining its distinguishability from real data by domain experts, ML classifiers, and Statistical Parametric Mapping (SPM). The benefits of incorporating augmented posture data into the learning process were exemplified by a deep autoencoder (AE) for automated feature representation. Results: Our findings highlight the challenge of differentiating synthetic data from real data for both experts and ML classifiers, underscoring the quality of synthetic data. This observation was also confirmed by SPM. By integrating synthetic data into AE training, the reconstruction error can be reduced compared to using only real data samples. Moreover, this study demonstrates the potential for reduced latent dimensions, while maintaining a reconstruction accuracy comparable to AEs trained exclusively on real data samples. Conclusion: This study emphasizes the prospects of harnessing generative AI to enhance ML tasks in the biomechanics domain.

Influence of Lateral Sitting Wedges on the Rasterstereographically Measured Scoliosis Angle in Patients Aged 10-18 Years with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional axial deviation of the spine diagnosed in adolescence. Despite a long daily sitting duration, there are no studies on whether scoliosis can be positively influenced by sitting on a seat wedge. For the prospective study, 99 patients with AIS were measured with the DIERS formetric III 4D average, in a standing position, on a level seat and with three differently inclined seat wedges (3°, 6° and 9°). The rasterstereographic parameters 'scoliosis angle' and 'lateral deviation RMS' were analysed. The side (ipsilateral/contralateral) on which the optimal correcting wedge was located in relation to the lumbar/thoraco-lumbar convexity was investigated. It was found that the greatest possible correction of scoliosis occurred with a clustering in wedges with an elevation on the ipsilateral side of the convexity. This clustering was significantly different from a uniform distribution (p < 0.001; chi-square = 35.697 (scoliosis angle); chi-square = 54.727 (lateral deviation RMS)). It should be taken into account that the effect of lateral seat wedges differs for individual types of scoliosis and degrees of severity. The possibility of having a positive effect on scoliosis while sitting holds great potential, which is worth investigating in follow-up studies.

Dynamic surface topography data for assessing intra- and interindividual variation of vertebral motion.

Spinal function is substantially related to the motion of the particular vertebrae and the spine as a whole. For systematic assessment of individual motion, data sets are required which cover the kinematics comprehensively. Additionally, the data should enable a comparison of inter- and intraindividual variation of vertebral orientation in dedicated motion tasks like gait. For this purpose, this article provides surface topography (ST) data which were acquired while the individual test persons were walking on a treadmill at three different speed levels (2 km/h, 3 km/h, 4 km/h). In each recording, ten full walking cycles were included per test case to enable a detailed analysis of motion patterns. The provided data reflects asymptomatic and pain-free volunteers. Each data set contains the vertebral orientation in all three motion directions for the vertebra prominens down to L4 as well as the pelvis. Additionally, spinal parameters like balance, slope, and lordosis / kyphosis parameters as well as an assignment of the motion data to single gait cycles are included. The complete raw data set without any preprocessing is provided. This allows to apply a broad range of further signal processing and evaluation steps in order to identify characteristic motion patterns as well as intra- and inter-individual variation of vertebral motion.

Creation and Evaluation of a Severity Classification of Hyperkyphosis and Hypolordosis for Exercise Therapy.

The rise in the occurrence of musculoskeletal disorders, such as thoracic hyperkyphosis (THK) or lumbar hypolordosis (LHL), is a result of demographic changes. Exercise therapy is an effective approach that can reduce related disabilities and costs. To ensure successful therapy, an individualized exercise program adapted to the severity of the disorder is expedient. Nevertheless, appropriate classification systems are scarce. This project aimed to develop and evaluate a severity classification focused on exercise therapy for patients with THK or LHL. A multilevel severity classification was developed and evaluated by means of an online survey. Reference limits of spinal shape angles were established by data from video rasterstereography of 201 healthy participants. A mean kyphosis angle of 50.03° and an average lordosis angle of 40.72° were calculated as healthy references. The strength of the multilevel classification consisting of the combination of subjective pain and objective spinal shape factors was confirmed by the survey (70% agreement). In particular, the included pain parameters were considered relevant by 78% of the experts. Even though the results of the survey provide important evidence for further analyses and optimization options of the classification system, the current version is still acceptable as therapeutic support.

Reference values and functional descriptions of transverse plane spinal dynamics during gait based on surface topography.

Spinal dynamics during gait have been of interest in research for many decades. Based on respective previous investigations, the pelvis is generally expected to be maximally forward rotated on the side of the reference leg at the beginning of each gait cycle and to reach its maximum counterrotation approximately at the end of the reference leg's stance phase. The pelvic-upper-thoracic-spine coordination converges towards an anti-phase movement pattern in high velocities during ambulation. The vertebral bodies around the seventh thoracic vertebra are considered to be an area of transition during human ambulation where no or at least little rotary motion can be observed. The respective cranial and caudal vertebrae meanwhile are expected to rotate conversely around this spinal point of intersection. However, these previous assumptions are based on scarce existing research, whereby only isolated vertebrae have been analyzed contemporaneously. Due to huge methodological differences in data capturing approaches, the results are additionally hardly comparable to each other and involved measurement procedures are often not implementable in clinical routines. Furthermore, none of the above-mentioned methods provided reference data for spinal motion during gait based on an appropriate number of healthy participants. Hence, the aim of this study was to present such reference data for spinal rotary motion of every vertebral body from C7 down to L4 and the pelvis derived from surface topographic back shape analyses in a cohort of 201 healthy participants walking on a treadmill at a given walking speed of 5 km/h. Additionally, the spine's functional movement behavior during gait should be described in the transverse plane based on data derived from this noninvasive, clinically suitable measurement approach and, in conclusion, the results shall be compared against those of previous research findings derived from other measurement techniques. Contrary to the previous functional understanding, the area of the mid-thoracic spine was found to demonstrate the largest amplitude of rotary motion of all investigated vertebrae and revealed an approximately counterrotated movement behavior compared to the rotary motion of the pelvis. In both directions, spinal rotation during gait seemed to be initiated by the pelvis. The overlying vertebrae followed in succession in the sense of an ongoing movement. Therefore, the point of intersection was not statically located in a specific anatomical section of the spine. Instead, it was found to be dynamic, ascending from one vertebra to the next from caudal to cranial in dependence of the pelvis's rotation initiation.

The INDICATE Knee expectations survey detects general patient treatment goals for total knee arthroplasty and the influence of demographic factors on patients expectations.

PURPOSE: Post-operative outcome after total knee arthroplasty (TKA) in the treatment of end-stage osteoarthritis correlates strongly with pre-operative impairment-driven patient treatment goals. However, a clinical tool for measuring patient treatment goals in correlation to impairments is still missing, which impedes patient-oriented indication in TKA. METHODS: Patients scheduled for TKA were recruited in four German hospitals. All patients were handed the INDICATE Knee Score pre-operatively. The score contains 31 treatment goals with respective impairments, subdivided into seven categories. They were asked to rank all treatment goals and impairments on a 3-point scale. Treatment goals and impairments were then checked for frequency of occurrence. Correlation of goal and impairment was tested. Analysis for associations of treatment goals and different cohort characteristics (age, sex, BMI) was conducted. RESULTS: 1.298 patients were included in the study. Seven treatment goals were categorised as "main goal" from more than 90% of all patients ("knee pain", "range of motion", "walking distance", "overall physical function", "climbing stairs", "quality of life", "implant survival"). Comparing age groups, there were significant associations towards higher expectations regarding working, physical and sports related treatment goals in younger patients (< 65y) ("ability to work" (P ≤ .001), "sports activities" (P ≤ .001), "sex life" (P ≤ .001), "dependence on help of others" (P = .015), "preventing secondary impairment" (P = .03), "dependence on walking aids" (P = .005)). Higher BMI resulted in increasing relevance of "weight reduction" (P ≤ .001), "climbing stairs" (P = .039) "global health status" (P = .015) and "long standing" (P = .007) as a "main goal". Analysis for differences in treatment goals regarding sex showed women choosing more treatment goals as "main goals" than men. CONCLUSION: Seven treatment goals which were expected by > 90% in our collective can be classified as general treatment goals for TKA. Demographic factors (age, sex, BMI) were significantly associated with patients' expectations for TKA. We conclude physicians should clearly assess their patients' demands prior to TKA to maximise post-operative outcome. LEVEL OF EVIDENCE: Prognostic Level III.

Consistency of vertebral motion and individual characteristics in gait sequences.

Vertebral motion reveals complex patterns, which are not yet understood in detail. This applies to vertebral kinematics in general but also to specific motion tasks like gait. For gait analysis, most of existing publications focus on averaging characteristics of recorded motion signals. Instead, this paper aims at analyzing intra- and inter-individual variation specifically and elaborating motion parameters, which are consistent during gait cycles of particular persons. For this purpose, a study design was utilized, which collected motion data from 11 asymptomatic test persons walking at different speed levels (2, 3, and 4 km/h). Acquisition of data was performed using surface topography. The motion signals were preprocessed in order to separate average vertebral orientations (neutral profiles) from basic gait cycles. Subsequently, a k-means clustering technique was applied to figure out, whether a discrimination of test persons was possible based on the preprocessed motion signals. The paper shows that each test sequence could be assigned to the particular test person without additional prior information. In particular, the neutral profiles appeared to be highly consistent intra-individually (across the gait cycles as well as speed levels), but substantially different between test persons. A full discrimination of test persons was achieved using the neutral profiles with respect to flexion/extension data. Based on this, these signals can be considered as individual characteristics for the particular test persons.

AI-Based Detection of Aspiration for Video-Endoscopy with Visual Aids in Meaningful Frames to Interpret the Model Outcome.

Disorders of swallowing often lead to pneumonia when material enters the airways (aspiration). Flexible Endoscopic Evaluation of Swallowing (FEES) plays a key role in the diagnostics of aspiration but is prone to human errors. An AI-based tool could facilitate this process. Recent non-endoscopic/non-radiologic attempts to detect aspiration using machine-learning approaches have led to unsatisfying accuracy and show black-box characteristics. Hence, for clinical users it is difficult to trust in these model decisions. Our aim is to introduce an explainable artificial intelligence (XAI) approach to detect aspiration in FEES. Our approach is to teach the AI about the relevant anatomical structures, such as the vocal cords and the glottis, based on 92 annotated FEES videos. Simultaneously, it is trained to detect boluses that pass the glottis and become aspirated. During testing, the AI successfully recognized the glottis and the vocal cords but could not yet achieve satisfying aspiration detection quality. While detection performance must be optimized, our architecture results in a final model that explains its assessment by locating meaningful frames with relevant aspiration events and by highlighting suspected boluses. In contrast to comparable AI tools, our framework is verifiable and interpretable and, therefore, accountable for clinical users.

Reference Values for 3D Spinal Posture Based on Videorasterstereographic Analyses of Healthy Adults.

Visual examinations are commonly used to analyze spinal posture. Even though they are simple and fast, their interrater reliability is poor. Suitable alternatives should be objective, non-invasive, valid and reliable. Videorasterstereography (VRS) is a corresponding method that is increasingly becoming established. However, there is a lack of reference data based on adequate numbers of participants and structured subgroup analyses according to sex and age. We used VRS to capture the spinal posture of 201 healthy participants (aged 18-70 years) divided into three age cohorts. Three-dimensional reference data are presented for the global spine parameters and for every vertebral body individually (C7-L4) (here called the specific spine parameters). The vertebral column was found to be systematically asymmetric in the transverse and the coronal planes. Graphical presentations of the vertebral body posture revealed systematic differences between the subgroups; however, large standard deviations meant that these differences were not significant. In contrast, several global parameters (e.g., thoracic kyphosis and lumbar lordosis) indicated differences between the analyzed subgroups. The findings confirm the importance of presenting reference data not only according to sex but also according to age in order to map physiological posture changes over the life span. The question also arises as to whether therapeutic approximations to an almost symmetrical spine are biomechanically desirable.

Comprehensive visualization of spinal motion in gait sequences based on surface topography.

Analysis of spinal motion is considered to be important to assess function of the human spine. Surface topography (ST) is a method to record the vertebral orientation in 3D. Such measurements can be performed in static but also in dynamic situations like gait or other motion tasks. However, dynamic ST measurements are hard to interpret due to their complexity. The main goal of this paper is to provide comprehensive visualization tools which allow a more intuitive and comprehensive interpretation n of such measurements. In particular, juxtaposition and superimposition techniques are utilized to emphasize differences in motion characteristics. The method was applied to a test series of 12 healthy volunteers walking on a treadmill at various speed levels. It could be shown that the visualization tools are helpful to compare different motion sequences including an analysis of intra- and interindividual variation. Based on these techniques, it could be shown that the profiles of vertebral orientation remain considerable constant when one person was walking at different speed levels whereas they differed substantially between the different individuals. In contrast, the motion amplitudes contained high intra- and interindividual variation, i.e. between speed levels and different test persons. In summary, the paper demonstrates that appropriate visualization tools are helpful to interpret ST measurements and cope with the complexity of these data sets. In particular, they can be used to compare different motion sequences in a more comprehensive way.

Machine learning techniques demonstrating individual movement patterns of the vertebral column: the fingerprint of spinal motion.

Surface topography systems enable the capture of spinal dynamic movement; however, it is unclear whether vertebral dynamics are unique enough to identify individuals. Therefore, in this study, we investigated whether the identification of individuals is possible based on dynamic spinal data. Three different data representations were compared (automated extracted features using contrastive loss and triplet loss functions, as well as simple descriptive statistics). High accuracies indicated the possible existence of a personal spinal 'fingerprint', therefore enabling subject recognition. The present work forms the basis for an objective comparison of subjects and the transfer of the method to clinical use cases.

Protective Effects of Therapeutic Neutrophil Depletion and Myeloperoxidase Inhibition on Left Ventricular Function and Remodeling in Myocardial Infarction.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI.

Evaluation of 3D vertebral and pelvic position by surface topography in asymptomatic females: presentation of normative reference data.

BACKGROUND: Deviations from a conventional physiologic posture are often a cause of complaint. According to current literature, the upright physiological spine posture exhibits inclinations in the sagittal plane but not in the coronal and transverse planes, but individual vertebral body positions of asymptomatic adults have rarely been described using surface topography. Therefore, this work aims to form a normative reference dataset for the thoracic and lumbar vertebral bodies and for the pelvis in all three planes in asymptomatic women. METHODS: In a prospective, cross-sectional, monocentric study, 100 pain-free asymptomatic women, aged 20-64 years were enrolled. Habitual standing positions of the trunk were measured using surface topography. Data were analyzed in all three planes. Age sub-analysis was: 1) ages ≤ 40 years and 2) ages ≥ 41 years. Two-sample t-tests were used for age comparisons of the vertebral bodies, vertebra prominence (VP)-L4, and global parameters. One-sample t-tests were used to test deviations from symmetrical zero positions of VP-L4. RESULTS: Coronal plane: on average, the vertebral bodies were tilted to the right between the VP and T4 (maximum: T2 - 1.8° ± 3.2), while between T6 and T11 they were tilted to the left (maximum: T7 1.1° ± 1.9). T5 and L2 were in a neutral position, overall depicting a mean right-sided lateral flexion from T2 to T7 (apex at T5). Sagittal plane: the kyphotic apex resided at T8 with - 0.5° ± 3.6 and the lumbar lordotic apex at L3 with - 2.1° ± 7.4. Transverse plane: participants had a mean vertebral body rotation to the right ranging from T6 to L4 (maximum: T11 - 2.2° ± 3.5). Age-specific differences were seen in the sagittal plane and had little effect on overall posture. CONCLUSIONS: Asymptomatic female volunteers standing in a habitual posture displayed an average vertebral rotation and lateral flexion to the right in vertebral segments T2-T7. The physiological asymmetrical posture of women could be considered in spinal therapies. With regard to spinal surgery, it should be clarified whether an approximation to an absolutely symmetrical posture is desirable from a biomechanical point of view? This data set can also be used as a reference in clinical practice. TRIAL REGISTRATION: This study was registered with WHO (INT: DRKS00010834) and approved by the responsible ethics committee at the Rhineland-Palatinate Medical Association (837.194.16).

Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation.

The six-transmembrane protein of prostate 2 (Stamp2) acts as an anti-inflammatory protein in macrophages by protecting from overt inflammatory signaling and Stamp2 deficiency accelerates atherosclerosis in mice. Herein, we describe an unexpected role of Stamp2 in polymorphonuclear neutrophils (PMN) and characterize Stamp2's protective effects in myocardial ischemic injury. In a murine model of ischemia and reperfusion (I/R), echocardiography and histological analyses revealed a pronounced impairment of cardiac function in hearts of Stamp2-deficient- (Stamp2-/- ) mice as compared to wild-type (WT) animals. This difference was driven by aggravated cardiac fibrosis, as augmented fibroblast-to-myofibroblast transdifferentiation was observed which was mediated by activation of the redox-sensitive p38 mitogen-activated protein kinase (p38 MAPK). Furthermore, we observed increased production of reactive oxygen species (ROS) in Stamp2-/- hearts after I/R, which is the likely cause for p38 MAPK activation. Although myocardial macrophage numbers were not affected by Stamp2 deficiency after I/R, augmented myocardial infiltration by polymorphonuclear neutrophils (PMN) was observed, which coincided with enhanced myeloperoxidase (MPO) plasma levels. Primary PMN isolated from Stamp2-/- animals exhibited a proinflammatory phenotype characterized by enhanced nuclear factor (NF)-κB activity and MPO secretion. To prove the critical role of PMN for the observed phenotype after I/R, antibody-mediated PMN depletion was performed in Stamp2-/- mice which reduced deterioration of LV function and adverse structural remodeling to WT levels. These data indicate a novel role of Stamp2 as an anti-inflammatory regulator of PMN and fibroblast-to-myofibroblast transdifferentiation in myocardial I/R injury.

Classification and Automated Interpretation of Spinal Posture Data Using a Pathology-Independent Classifier and Explainable Artificial Intelligence (XAI).

Clinical classification models are mostly pathology-dependent and, thus, are only able to detect pathologies they have been trained for. Research is needed regarding pathology-independent classifiers and their interpretation. Hence, our aim is to develop a pathology-independent classifier that provides prediction probabilities and explanations of the classification decisions. Spinal posture data of healthy subjects and various pathologies (back pain, spinal fusion, osteoarthritis), as well as synthetic data, were used for modeling. A one-class support vector machine was used as a pathology-independent classifier. The outputs were transformed into a probability distribution according to Platt's method. Interpretation was performed using the explainable artificial intelligence tool Local Interpretable Model-Agnostic Explanations. The results were compared with those obtained by commonly used binary classification approaches. The best classification results were obtained for subjects with a spinal fusion. Subjects with back pain were especially challenging to distinguish from the healthy reference group. The proposed method proved useful for the interpretation of the predictions. No clear inferiority of the proposed approach compared to commonly used binary classifiers was demonstrated. The application of dynamic spinal data seems important for future works. The proposed approach could be useful to provide an objective orientation and to individually adapt and monitor therapy measures pre- and post-operatively.

General method for automated feature extraction and selection and its application for gender classification and biomechanical knowledge discovery of sex differences in spinal posture during stance and gait.

Modern technologies enable to capture multiple biomechanical parameters often resulting in relational data. The current work proposes a generally applicable method comprising automated feature extraction, ensemble feature selection and classification to best capture the potentials of the data also for generating new biomechanical knowledge. Its benefits are demonstrated in the concrete biomechanically and medically relevant use case of gender classification based on spinal data for stance and gait. Very good results for accuracy were obtained using gait data. Dynamic movements of the lumbar spine in sagittal and frontal plane and of the pelvis in frontal plane best map gender differences.

The participants' perspective: how biographic-narrative intervention influences identity negotiation and quality of life in aphasia.

BACKGROUND: People with aphasia experience a pronounced decrease in quality of life (QoL). Beyond that identity negotiation is hindered, which is crucial for QoL. Biographic-narrative approaches use life story telling to support identity (re)development after disruptive events like stroke. Because of the language deficits inherent in aphasia such 'talk-based' approaches have to be modified for an optimal use. AIMS: To evaluate an adapted interdisciplinary biographic-narrative intervention using quantitative measures of health-related quality of life (HRQL) and mood. Additionally, semi-structured interviews were conducted to gain a deeper understanding of identity development processes in people with aphasia. METHODS & PROCEDURES: Twenty-seven participants with various types of chronic aphasia were enrolled. The biographic narrative intervention consisted of five face-to-face in-depth interviews and seven group sessions conducted over 10 weeks in a mixed-method design with pre- and post-tests and a follow-up assessment 3 months post-intervention. For quantitative evaluation the Aachen Life Quality Inventory (ALQI), the Satisfaction with Life Scale (SWLS) and the Visual Analog Mood Scales (VAMS) were used. Semi-structured interviews were conducted post-treatment, including questions concerning the participants' experiences with the intervention and identity change. Results were analysed using interpretative principles from Grounded Theory. OUTCOMES & RESULTS: For all 27 participants, we found significant and stable growth in HRQL. Self-reported states of mood also improved. As expected, overall cognitively based life satisfaction did not change. The interviews revealed two main categories: 'evaluation of the face-to-face interviews' and 'evaluation of the group sessions'. Further analysis found four overlapping main themes which were identified as identity issues: agency, control, disease concept and doing things. CONCLUSIONS & IMPLICATIONS: Our quantitative and qualitative results demonstrated the benefits associated with the biographic-narrative intervention. The participants' sense of self changed through the approach. The findings provide foundations for future work using biographic narrative interventions to influence QoL and identity renegotiation in people with aphasia.

Endothelin receptor B protects granulocyte macrophage colony-stimulating factor mRNA from degradation.

Evidence is lacking on the differential effects of the two therapeutic concepts of endothelin receptor antagonists (ERAs): the blockade of only the endothelin receptor A (ETAR; selective antagonism) versus both ETAR and endothelin receptor B (ETBR; dual blockade). Ambrisentan, a selective ERA, and bosentan, a dual blocker, are both available for therapy. We hypothesized that there are differences in the potential of ERAs to ameliorate inflammatory processes in human airway smooth muscle cells (HASMCs) and aimed to unravel underlying mechanisms. We used HASMC culture, enzyme-linked immunosorbent assay, and quantitative reverse-transcription polymerase chain reaction. Tumor necrosis factor α (TNFα) induced transcription and expression of chemokine (C-X-C motif) ligand 2 (CXCL2), chemokine (C-X-C motif) ligand 3 (CXCL3), granulocyte macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase 12 (MMP12) in HASMCs. In concentration-response experiments, bosentan led to a significantly greater reduction of GM-CSF and MMP12 protein release than ambrisentan, whereas there was no significant difference in their effect on GM-CSF and MMP12 mRNA. Both ERAs reduced CXCL3 protein and mRNA equally but had no effect on CXCL2. Blocking mitogen-activated protein kinases revealed that both ETAR and ETBR signal through p38 mitogen-activated protein kinase, but ETBR also signals through extracellular signal-regulated kinase (ERK) 1/2 to induce GM-CSF expression. In the presence of the transcription inhibitor actinomycin D, bosentan, but not ambrisentan, reduced GM-CSF but not MMP12 or CXCL3 mRNA. In conclusion, blockade of each endothelin receptor subtype reduces GM-CSF transcription, but blocking ETBR additionally protects GM-CSF mRNA from degradation via ERK-1/2. Accordingly, blocking both ETAR and ETBR leads to a stronger reduction of TNFα-induced GM-CSF protein expression. This mechanism might be specific to GM-CSF. Our data stress the anti-inflammatory potential of ERA and warrant further investigation of their utility in chronic inflammatory airway diseases.

Direct effects of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia.

OBJECTIVES: The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. METHODS: Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. RESULTS: The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. CONCLUSION: For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only.