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- Fakultät für Gesundheitswissenschaften (28) (remove)
Frailty assessment is recommended before elective transcatheter aortic valve implantation (TAVI) to determine post-interventional prognosis. Several studies have investigated frailty in TAVI-patients using numerous assessments; however, it remains unclear which is the most appropriate tool for clinical practice. Therefore, we evaluate which frailty assessment is mainly used and meaningful for ≤30-day and ≥1-year prognosis in TAVI patients. Randomized controlled or observational studies (prospective/retrospective) investigating all-cause mortality in older (≥70 years) TAVI patients were identified (PubMed; May 2020). In total, 79 studies investigating frailty with 49 different assessments were included. As single markers of frailty, mostly gait speed (23 studies) and serum albumin (16 studies) were used. Higher risk of 1-year mortality was predicted by slower gait speed (highest Hazard Ratios (HR): 14.71; 95% confidence interval (CI) 6.50–33.30) and lower serum albumin level (highest HR: 3.12; 95% CI 1.80–5.42). Composite indices (five items; seven studies) were associated with 30-day (highest Odds Ratio (OR): 15.30; 95% CI 2.71–86.10) and 1-year mortality (highest OR: 2.75; 95% CI 1.55–4.87). In conclusion, single markers of frailty, in particular gait speed, were widely used to predict 1-year mortality. Composite indices were appropriate, as well as a comprehensive assessment of frailty. View Full-Text
Frailty assessment is recommended before elective transcatheter aortic valve implantation (TAVI) to determine post-interventional prognosis. Several studies have investigated frailty in TAVI-patients using numerous assessments; however, it remains unclear which is the most appropriate tool for clinical practice. Therefore, we evaluate which frailty assessment is mainly used and meaningful for ≤30-day and ≥1-year prognosis in TAVI patients. Randomized controlled or observational studies (prospective/retrospective) investigating all-cause mortality in older (≥70 years) TAVI patients were identified (PubMed; May 2020). In total, 79 studies investigating frailty with 49 different assessments were included. As single markers of frailty, mostly gait speed (23 studies) and serum albumin (16 studies) were used. Higher risk of 1-year mortality was predicted by slower gait speed (highest Hazard Ratios (HR): 14.71; 95% confidence interval (CI) 6.50–33.30) and lower serum albumin level (highest HR: 3.12; 95% CI 1.80–5.42). Composite indices (five items; seven studies) were associated with 30-day (highest Odds Ratio (OR): 15.30; 95% CI 2.71–86.10) and 1-year mortality (highest OR: 2.75; 95% CI 1.55–4.87). In conclusion, single markers of frailty, in particular gait speed, were widely used to predict 1-year mortality. Composite indices were appropriate, as well as a comprehensive assessment of frailty. View Full-Text
Jenseits der Klinik
(2021)
Unser Beitrag stellt ein interaktives Ethik-Konzept vor, das in Zusammenarbeit der BruderhausDiakonie Reutlingen und der Universität Tübingen entwickelt wurde, um den Eigenheiten und Bedarfen einer komplexen Organisationsstruktur gerecht zu werden, die mehrere Geschäftsfelder und Standorte unter sich vereint. Wir skizzieren die Grundzüge des interaktiven Nijmegener Modells, in dem die Kooperation eines auf Leitungsebene angesiedelten Komitees und situationsbezogener Fallbesprechungen ein fruchtbares Zusammenspiel zweier unverzichtbarer Reflexionsweisen bewirken soll („Top-Down“/„Bottom-Up“). Wir zeigen auf, welche Herausforderungen sich bei der Implementierung dieses Modells in die konkrete Aufbauorganisation der BruderhausDiakonie ergaben, und mit welchen konzeptionellen oder „implementationstechnischen“ Mitteln ihnen begegnet wurde. Im Zentrum steht dabei die Erweiterung des Nijmegener Modells um ein Verbindungselement, welches die Zusammenarbeit zwischen zentralem Ausschuss und dezentralen Fallbesprechungen koordiniert und das interaktive Moment des Modells erst ermöglicht.
This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances reversal learning and augments noradrenergic biomarkers (i.e., pupil size, cortisol, and salivary alpha-amylase [sAA]). We also explored the effect of taVNS on respiratory rate and cardiac vagal activity (CVA). Seventy-one participants received stimulation of either the cymba concha (taVNS) or the earlobe (sham) of the left ear. After learning a series of cue-outcome associations, the stimulation was applied before and throughout a reversal phase in which cue-outcome associations were changed for some (reversal), but not for other (distractor) cues. Tonic pupil size, salivary cortisol, sAA, respiratory rate, and CVA were assessed at different time points. Contrary to our hypothesis, taVNS was not associated with an overall improvement in performance on the reversal task. Compared to sham, the taVNS group performed worse for distractor than reversal cues. taVNS did not increase tonic pupil size and sAA. Only post hoc analyses indicated that the cortisol decline was steeper in the sham compared to the taVNS group. Exploratory analyses showed that taVNS decreased respiratory rate but did not affect CVA. The weak and unexpected effects found in this study might relate to the lack of parameters optimization for taVNS and invite to further investigate the effect of taVNS on cortisol and respiratory rate.
The PNPLA3 reference single-nucleotide polymorphism rs738409 has been identified as a predisposing factor for nonalcoholic fatty liver disease. A simple method based on PCR and restriction fragment length polymorphism (RFLP) analysis had been published to detect the nonpathogenic allele PNPLA3 rs738409 variant. The presence of the pathogenic variant was deduced by the indigestibility of the corresponding PCR product with BtsCI recognizing the nonpathogenic allele. However, one cannot exclude that an enzymatic reaction does not occur for other, more trivial, reasons. For safe and secure detection of the pathogenic PNPLA3 rs738409, we have further developed the PCR-restriction fragment length polymorphism method by adding a second restriction enzyme digest, clearly identifying the correct PNPLA3 alleles and in particular the pathogenic variant. <br /> METHOD SUMMARY <br /> The method presented here represents an improved genetic diagnosis of the PNPLA3 rs738409 alleles based on conventional and inexpensive molecular biological methods. We used methodology based on PCR and restriction fragment length polymorphisms and clearly identified both described alleles by the use of two restriction enzymes. Digestion of individuals' specific PNPLA3 PCR fragments with both enzymes in independent reactions clearly showed the PNPLA3 rs738409 genotype.
Nonparametric goodness-of-fit testing for parametric covariate models in pharmacometric analyses
(2021)
The characterization of covariate effects on model parameters is a crucial step during pharmacokinetic/pharmacodynamic analyses. Although covariate selection criteria have been studied extensively, the choice of the functional relationship between covariates and parameters, however, has received much less attention. Often, a simple particular class of covariate-to-parameter relationships (linear, exponential, etc.) is chosen ad hoc or based on domain knowledge, and a statistical evaluation is limited to the comparison of a small number of such classes. Goodness-of-fit testing against a nonparametric alternative provides a more rigorous approach to covariate model evaluation, but no such test has been proposed so far. In this manuscript, we derive and evaluate nonparametric goodness-of-fit tests for parametric covariate models, the null hypothesis, against a kernelized Tikhonov regularized alternative, transferring concepts from statistical learning to the pharmacological setting. The approach is evaluated in a simulation study on the estimation of the age-dependent maturation effect on the clearance of a monoclonal antibody. Scenarios of varying data sparsity and residual error are considered. The goodness-of-fit test correctly identified misspecified parametric models with high power for relevant scenarios. The case study provides proof-of-concept of the feasibility of the proposed approach, which is envisioned to be beneficial for applications that lack well-founded covariate models.
Extracellular vesicles: potential mediators of psychosocial stress contribution to osteoporosis?
(2021)
Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
Extracellular vesicles
(2021)
Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
Background
Depression is one of the key factors contributing to difficulties in one’s ability to work, and serves as one of the major reasons why employees apply for psychotherapy and receive insurance subsidization of treatments. Hence, an increasing and growing number of studies rely on workability assessment scales as their primary outcome measure. The Work and Social Assessment Scale (WSAS) has been documented as one of the most psychometrically reliable and valid tools especially developed to assess workability and social functioning in patients with mental health problems. Yet, the application of the WSAS in Germany has been limited due to the paucity of a valid questionnaire in the German language. The objective of the present study was to translate the WSAS, as a brief and easy administrable tool into German and test its psychometric properties in a sample of adults with depression.
Methods
Two hundred seventy-seven patients (M = 48.3 years, SD = 11.1) with mild to moderately severe depression were recruited. A multistep translation from English into the German language was performed and the factorial validity, criterion validity, convergent validity, discriminant validity, internal consistency, and floor and ceiling effects were examined.
Results
The confirmatory factor analysis results confirmed the one-factor structure of the WSAS. Significant correlations with the WHODAS 2–0 questionnaire, a measure of functionality, demonstrated good convergent validity. Significant correlations with depression and quality of life demonstrated good criterion validity. The WSAS also demonstrated strong internal consistency (α = .89), and the absence of floor and ceiling effects indicated good sensitivity of the instrument.
Conclusions
The results of the present study demonstrated that the German version of the WSAS has good psychometric properties comparable to other international versions of this scale. The findings recommend a global assessment of psychosocial functioning with the sum score of the WSAS.
Background
Depression is one of the key factors contributing to difficulties in one’s ability to work, and serves as one of the major reasons why employees apply for psychotherapy and receive insurance subsidization of treatments. Hence, an increasing and growing number of studies rely on workability assessment scales as their primary outcome measure. The Work and Social Assessment Scale (WSAS) has been documented as one of the most psychometrically reliable and valid tools especially developed to assess workability and social functioning in patients with mental health problems. Yet, the application of the WSAS in Germany has been limited due to the paucity of a valid questionnaire in the German language. The objective of the present study was to translate the WSAS, as a brief and easy administrable tool into German and test its psychometric properties in a sample of adults with depression.
Methods
Two hundred seventy-seven patients (M = 48.3 years, SD = 11.1) with mild to moderately severe depression were recruited. A multistep translation from English into the German language was performed and the factorial validity, criterion validity, convergent validity, discriminant validity, internal consistency, and floor and ceiling effects were examined.
Results
The confirmatory factor analysis results confirmed the one-factor structure of the WSAS. Significant correlations with the WHODAS 2–0 questionnaire, a measure of functionality, demonstrated good convergent validity. Significant correlations with depression and quality of life demonstrated good criterion validity. The WSAS also demonstrated strong internal consistency (α = .89), and the absence of floor and ceiling effects indicated good sensitivity of the instrument.
Conclusions
The results of the present study demonstrated that the German version of the WSAS has good psychometric properties comparable to other international versions of this scale. The findings recommend a global assessment of psychosocial functioning with the sum score of the WSAS.
Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E-2 (PGE(2)) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE(2) to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE(2) synthesis. PGE(2) in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE(2) in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.
Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive-compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD>SIB>HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.
Risikokommunikation spielt eine zentrale Rolle in Public-Health-Notlagen: Sie muss informierte Entscheidungen ermöglichen, schützendes bzw. lebenserhaltendes Verhalten fördern und das Vertrauen in öffentliche Institutionen bewahren. Zudem müssen Unsicherheiten über wissenschaftliche Erkenntnisse transparent benannt werden, irrationale Ängste und Gerüchte entkräftet werden. Risikokommunikation sollte die Bevölkerung partizipativ einbeziehen. Ihre Risikowahrnehmung und -kompetenz müssen kontinuierlich erfasst werden. In der aktuellen Pandemie der Coronavirus-Krankheit 2019 (COVID-19) ergeben sich spezifische Herausforderungen für die Risikokommunikation.
Der Wissensstand zu vielen wichtigen Aspekten, die COVID-19 betreffen, war und ist oftmals unsicher oder vorläufig, z. B. zu Übertragung, Symptomen, Langzeitfolgen und Immunität. Die Kommunikation ist durch wissenschaftliche Sprache sowie eine Vielzahl von Kennzahlen und Statistiken geprägt, was die Verständlichkeit erschweren kann. Neben offiziellen Mitteilungen und Einschätzungen von Expertinnen und Experten wird über COVID-19 in großem Umfang in sozialen Medien kommuniziert, dabei werden auch Fehlinformationen und Spekulationen verbreitet; diese „Infodemie“ erschwert die Risikokommunikation.
Nationale wie internationale Forschungsprojekte sollen helfen, die Risikokommunikation zu COVID-19 zielgruppenspezifischer und effektiver zu machen. Dazu gehören u. a. explorative Studien zum Umgang mit COVID-19-bezogenen Informationen, das COVID-19 Snapshot Monitoring (COSMO), ein regelmäßig durchgeführtes Onlinesurvey zu Risikowahrnehmung und Schutzverhalten sowie eine interdisziplinäre qualitative Studie, die die Konzeption, Umsetzung und Wirksamkeit von Risikokommunikationsstrategien vergleichend in 4 Ländern untersucht.
Background
Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country.
Methods
The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program.
The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG).
Discussion
An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers.
Trial registration
DRKS, DRKS00020373. Registered on 15 April 2020
Development of chronic pain after a low back pain episode is associated with increased pain sensitivity, altered pain processing mechanisms and the influence of psychosocial factors. Although there is some evidence that multimodal therapy (such as behavioral or motor control therapy) may be an important therapeutic strategy, its long-term effect on pain reduction and psychosocial load is still unclear. Prospective longitudinal designs providing information about the extent of such possible long-term effects are missing. This study aims to investigate the long-term effects of a homebased uni- and multidisciplinary motor control exercise program on low back pain intensity, disability and psychosocial variables. 14 months after completion of a multicenter study comparing uni- and multidisciplinary exercise interventions, a sample of one study center (n = 154) was assessed once more. Participants filled in questionnaires regarding their low back pain symptoms (characteristic pain intensity and related disability), stress and vital exhaustion (short version of the Maastricht Vital Exhaustion Questionnaire), anxiety and depression experiences (the Hospital and Anxiety Depression Scale), and pain-related cognitions (the Fear Avoidance Beliefs Questionnaire). Repeated measures mixed ANCOVAs were calculated to determine the long-term effects of the interventions on characteristic pain intensity and disability as well as on the psychosocial variables. Fifty four percent of the sub-sample responded to the questionnaires (n = 84). Longitudinal analyses revealed a significant long-term effect of the exercise intervention on pain disability. The multidisciplinary group missed statistical significance yet showed a medium sized long-term effect. The groups did not differ in their changes of the psychosocial variables of interest. There was evidence of long-term effects of the interventions on pain-related disability, but there was no effect on the other variables of interest. This may be partially explained by participant's low comorbidities at baseline. Results are important regarding costless homebased alternatives for back pain patients and prevention tasks. Furthermore, this study closes the gap of missing long-term effect analysis in this field.
Ethik-Komitees gehören zum festen Bestandteil des Ethikmanagements und der Organisationsethik in klinischen Einrichtungen des Gesundheitswesens. Entsprechende Ethikstrukturen und die damit verbundenen Angebote stoßen hinsichtlich ihrer Wirksamkeit allerdings an ihre Grenzen. Ihre Arbeitsweisen sind häufig reaktiv und eine Verankerung in den entsprechenden Organisationsebenen fehlt. Ausgehend von diesen Limitationen der klinischen Ethikberatung hat sich die multiprofessionelle „Arbeitsgruppe Ethik“ am Universitätsklinikum Tübingen (UKT) um die Konzeption und Implementierung eines neuen Ansatzes zur nachhaltigen Integration von ethischen Reflexions- und Entscheidungsprozessen auf den Stationen des UKT bemüht. Mit dem Tübinger Modell der Ethikbeauftragten der Station verfolgt sie ein Pilotprojekt, das speziell geschulte Pflegekräfte aus allen Stationen des UKT als AnsprechpartnerInnen für ethische Fragen einsetzt. Damit stellen die Ethikbeauftragten eine Erweiterung zu etablierten Strukturen der Ethikberatung dar und ergänzen vorhandene Top-Down-Strategien. Der vorliegende Beitrag stellt die Zielsetzungen des Tübinger Modells dar und schildert erste Erfahrungen in der Umsetzung. Neben der Einbettung in organisationale Strukturen der Ethikberatung werden die stationsinternen und stationsübergreifenden Aufgaben der Ethikbeauftragten dargestellt. Zudem wird das Qualifikationsprogramm für Ethikbeauftragte (Basis- und Aufbauschulung) sowie ein Train-the-Trainer-Konzept vorgestellt, welche eine vertiefende Entwicklung von pflege- und medizinethischer Kompetenzen unterstützen und Sicherheit in den stationsbezogenen Reflexions- und Entscheidungsprozessen vermitteln.
Background: The relationship between exercise-induced intratendinous blood flow (IBF) and tendon pathology or training exposure is unclear.
Objective: This study investigates the acute effect of running exercise on sonographic detectable IBF in healthy and tendinopathic Achilles tendons (ATs) of runners and recreational participants.
Methods: 48 participants (43 ± 13 years, 176 ± 9 cm, 75 ± 11 kg) performed a standardized submaximal 30-min constant load treadmill run with Doppler ultrasound “Advanced dynamic flow” examinations before (Upre) and 5, 30, 60, and 120 min (U5-U120) afterward. Included were runners (>30 km/week) and recreational participants (<10 km/week) with healthy (Hrun, n = 10; Hrec, n = 15) or tendinopathic (Trun, n = 13; Trec, n = 10) ATs. IBF was assessed by counting number [n] of intratendinous vessels. IBF data are presented descriptively (%, median [minimum to maximum range] for baseline-IBF and IBF-difference post-exercise). Statistical differences for group and time point IBF and IBF changes were analyzed with Friedman and Kruskal-Wallis ANOVA (α = 0.05).
Results: At baseline, IBF was detected in 40% (3 [1–6]) of Hrun, in 53% (4 [1–5]) of Hrec, in 85% (3 [1–25]) of Trun, and 70% (10 [2–30]) of Trec. At U5 IBF responded to exercise in 30% (3 [−1–9]) of Hrun, in 53% (4 [−2–6]) of Hrec, in 70% (4 [−10–10]) of Trun, and in 80% (5 [1–10]) of Trec. While IBF in 80% of healthy responding ATs returned to baseline at U30, IBF remained elevated until U120 in 60% of tendinopathic ATs. Within groups, IBF changes from Upre-U120 were significant for Hrec (p < 0.01), Trun (p = 0.05), and Trec (p < 0.01). Between groups, IBF changes in consecutive examinations were not significantly different (p > 0.05) but IBF-level was significantly higher at all measurement time points in tendinopathic versus healthy ATs (p < 0.05).
Conclusion: Irrespective of training status and tendon pathology, running leads to an immediate increase of IBF in responding tendons. This increase occurs shortly in healthy and prolonged in tendinopathic ATs. Training exposure does not alter IBF occurrence, but IBF level is elevated in tendon pathology. While an immediate exercise-induced IBF increase is a physiological response, prolonged IBF is considered a pathological finding associated with Achilles tendinopathy.
Background: The relationship between exercise-induced intratendinous blood flow (IBF) and tendon pathology or training exposure is unclear.
Objective: This study investigates the acute effect of running exercise on sonographic detectable IBF in healthy and tendinopathic Achilles tendons (ATs) of runners and recreational participants.
Methods: 48 participants (43 ± 13 years, 176 ± 9 cm, 75 ± 11 kg) performed a standardized submaximal 30-min constant load treadmill run with Doppler ultrasound “Advanced dynamic flow” examinations before (Upre) and 5, 30, 60, and 120 min (U5-U120) afterward. Included were runners (>30 km/week) and recreational participants (<10 km/week) with healthy (Hrun, n = 10; Hrec, n = 15) or tendinopathic (Trun, n = 13; Trec, n = 10) ATs. IBF was assessed by counting number [n] of intratendinous vessels. IBF data are presented descriptively (%, median [minimum to maximum range] for baseline-IBF and IBF-difference post-exercise). Statistical differences for group and time point IBF and IBF changes were analyzed with Friedman and Kruskal-Wallis ANOVA (α = 0.05).
Results: At baseline, IBF was detected in 40% (3 [1–6]) of Hrun, in 53% (4 [1–5]) of Hrec, in 85% (3 [1–25]) of Trun, and 70% (10 [2–30]) of Trec. At U5 IBF responded to exercise in 30% (3 [−1–9]) of Hrun, in 53% (4 [−2–6]) of Hrec, in 70% (4 [−10–10]) of Trun, and in 80% (5 [1–10]) of Trec. While IBF in 80% of healthy responding ATs returned to baseline at U30, IBF remained elevated until U120 in 60% of tendinopathic ATs. Within groups, IBF changes from Upre-U120 were significant for Hrec (p < 0.01), Trun (p = 0.05), and Trec (p < 0.01). Between groups, IBF changes in consecutive examinations were not significantly different (p > 0.05) but IBF-level was significantly higher at all measurement time points in tendinopathic versus healthy ATs (p < 0.05).
Conclusion: Irrespective of training status and tendon pathology, running leads to an immediate increase of IBF in responding tendons. This increase occurs shortly in healthy and prolonged in tendinopathic ATs. Training exposure does not alter IBF occurrence, but IBF level is elevated in tendon pathology. While an immediate exercise-induced IBF increase is a physiological response, prolonged IBF is considered a pathological finding associated with Achilles tendinopathy.
Following stroke, neuronal death takes place both in the infarct region and in brain areas distal to the lesion site including the hippocampus. The hippocampus is critically involved in learning and memory processes and continuously generates new neurons. Dysregulation of adult neurogenesis may be associated with cognitive decline after a stroke lesion. In particular, proliferation of precursor cells and the formation of new neurons are increased after lesion. Within the first week, many new precursor cells die during development. How dying precursors are removed from the hippocampus and to what extent phagocytosis takes place after stroke is still not clear. Here, we evaluated the effect of a prefrontal stroke lesion on the phagocytic activity of microglia in the dentate gyrus (DG) of the hippocampus. Three-months-old C57BL/6J mice were injected once with the proliferation marker BrdU (250 mg/kg) 6 hr after a middle cerebral artery occlusion or sham surgery. The number of apoptotic cells and the phagocytic capacity of the microglia were evaluated by means of immunohistochemistry, confocal microscopy, and 3D-reconstructions. We found a transient but significant increase in the number of apoptotic cells in the DG early after stroke, associated with impaired removal by microglia. Interestingly, phagocytosis of newly generated precursor cells was not affected. Our study shows that a prefrontal stroke lesion affects phagocytosis of apoptotic cells in the DG, a region distal to the lesion core. Whether disturbed phagocytosis might contribute to inflammatory- and maladaptive processes including cognitive impairment following stroke needs to be further investigated.
Cardiac rehabilitation
(2021)
Emotional memories are better remembered than neutral ones, but the mechanisms leading to this memory bias are not well under-stood in humans yet. Based on animal research, it is suggested that the memory-enhancing effect of emotion is based on central nor-adrenergic release, which is triggered by afferent vagal nerve activation. To test the causal link between vagus nerve activation and emotional memory in humans, we applied continuous noninvasive transcutaneous auricular vagus nerve stimulation (taVNS) during exposure to emotional arousing and neutral scenes and tested subsequent, long-term recognition memory after 1 week. We found that taVNS, compared with sham, increased recollection-based memory performance for emotional, but not neutral, material. These findings were complemented by larger recollection-related brain potentials (parietal ERP Old/New effect) during retrieval of emotional scenes encoded under taVNS, compared with sham. Furthermore, brain potentials recorded during encoding also revealed that taVNS facilitated early attentional discrimination between emotional and neutral scenes. Extending animal research, our behavioral and neu-ral findings confirm a modulatory influence of the vagus nerve in emotional memory formation in humans.
Electrical muscle stimulation (EMS) is an increasingly popular training method and has become the focus of research in recent years. New EMS devices offer a wide range of mobile applications for whole-body EMS (WB-EMS) training, e.g., the intensification of dynamic low-intensity endurance exercises through WB-EMS. The present study aimed to determine the differences in exercise intensity between WB-EMS-superimposed and conventional walking (EMS-CW), and CON and WB-EMS-superimposed Nordic walking (WB-EMS-NW) during a treadmill test. Eleven participants (52.0 ± years; 85.9 ± 7.4 kg, 182 ± 6 cm, BMI 25.9 ± 2.2 kg/m2) performed a 10 min treadmill test at a given velocity (6.5 km/h) in four different test situations, walking (W) and Nordic walking (NW) in both conventional and WB-EMS superimposed. Oxygen uptake in absolute (VO2) and relative to body weight (rel. VO2), lactate, and the rate of perceived exertion (RPE) were measured before and after the test. WB-EMS intensity was adjusted individually according to the feedback of the participant. The descriptive statistics were given in mean ± SD. For the statistical analyses, one-factorial ANOVA for repeated measures and two-factorial ANOVA [factors include EMS, W/NW, and factor combination (EMS*W/NW)] were performed (α = 0.05). Significant effects were found for EMS and W/NW factors for the outcome variables VO2 (EMS: p = 0.006, r = 0.736; W/NW: p < 0.001, r = 0.870), relative VO2 (EMS: p < 0.001, r = 0.850; W/NW: p < 0.001, r = 0.937), and lactate (EMS: p = 0.003, r = 0.771; w/NW: p = 0.003, r = 0.764) and both the factors produced higher results. However, the difference in VO2 and relative VO2 is within the range of biological variability of ± 12%. The factor combination EMS*W/NW is statistically non-significant for all three variables. WB-EMS resulted in the higher RPE values (p = 0.035, r = 0.613), RPE differences for W/NW and EMS*W/NW were not significant. The current study results indicate that WB-EMS influences the parameters of exercise intensity. The impact on exercise intensity and the clinical relevance of WB-EMS-superimposed walking (WB-EMS-W) exercise is questionable because of the marginal differences in the outcome variables.
Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk.
Secretory Wnt trafficking can be studied in the polarized epithelial monolayer of Drosophila wing imaginal discs (WID). In this tissue, Wg (Drosophila Wnt-I) is presented on the apical surface of its source cells before being internalized into the endosomal pathway. Long-range Wg secretion and spread depend on secondary secretion from endosomal compartments, but the exact post-endocytic fate of Wg is poorly understood. Here, we summarize and present three protocols for the immunofluorescencebased visualization and quantitation of different pools of intracellular and extracellular Wg in WID: (1) steady-state extracellular Wg; (2) dynamic Wg trafficking inside endosomal compartments; and (3) dynamic Wg release to the cell surface. Using a genetic driver system for gene manipulation specifically at the posterior part of the WID (EnGal4) provides a robust internal control that allows for direct comparison of signal intensities of control and manipulated compartments of the same WID. Therefore, it also circumvents the high degree of staining variability usually associated with whole-tissue samples. In combination with the genetic manipulation of Wg pathway components that is easily feasible in Drosophila, these methods provide a tool-set for the dissection of secretory Wg trafficking and can help us to understand how Wnt proteins travel along endosomal compartments for short-and long-range signal secretion.