TY - JOUR A1 - Almeida, Mara A1 - Ranisch, Robert T1 - Beyond safety: mapping the ethical debate on heritable genome editing interventions JF - Humanities and Social Sciences Communications N2 - Genetic engineering has provided humans the ability to transform organisms by direct manipulation of genomes within a broad range of applications including agriculture (e.g., GM crops), and the pharmaceutical industry (e.g., insulin production). Developments within the last 10 years have produced new tools for genome editing (e.g., CRISPR/Cas9) that can achieve much greater precision than previous forms of genetic engineering. Moreover, these tools could offer the potential for interventions on humans and for both clinical and non-clinical purposes, resulting in a broad scope of applicability. However, their promising abilities and potential uses (including their applicability in humans for either somatic or heritable genome editing interventions) greatly increase their potential societal impacts and, as such, have brought an urgency to ethical and regulatory discussions about the application of such technology in our society. In this article, we explore different arguments (pragmatic, sociopolitical and categorical) that have been made in support of or in opposition to the new technologies of genome editing and their impact on the debate of the permissibility or otherwise of human heritable genome editing interventions in the future. For this purpose, reference is made to discussions on genetic engineering that have taken place in the field of bioethics since the 1980s. Our analysis shows that the dominance of categorical arguments has been reversed in favour of pragmatic arguments such as safety concerns. However, when it comes to involving the public in ethical discourse, we consider it crucial widening the debate beyond such pragmatic considerations. In this article, we explore some of the key categorical as well sociopolitical considerations raised by the potential uses of heritable genome editing interventions, as these considerations underline many of the societal concerns and values crucial for public engagement. We also highlight how pragmatic considerations, despite their increasing importance in the work of recent authoritative sources, are unlikely to be the result of progress on outstanding categorical issues, but rather reflect the limited progress on these aspects and/or pressures in regulating the use of the technology. KW - Ethics KW - Medical humanities KW - Science, technology and society Y1 - 2022 U6 - https://doi.org/10.1057/s41599-022-01147-y SN - 2662-9992 VL - 9 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Baritello, Omar A1 - Salzwedel, Annett A1 - Sündermann, Simon A1 - Niebauer, Josef A1 - Völler, Heinz T1 - The Pandora's Box of frailty assessments: Which is the best for clinical purposes in TAVI patients? A critical review JF - Journal of Clinical Medicine N2 - 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 KW - frailty tool KW - TAVI KW - older patients KW - elderly KW - cardiology KW - mortality Y1 - 2021 U6 - https://doi.org/10.3390/jcm10194506 SN - 2077-0383 VL - 10 SP - 1 EP - 17 PB - MDPI CY - Basel ET - 19 ER - TY - JOUR A1 - Baritello, Omar A1 - Stein, Hanna A1 - Wolff, Lara Luisa A1 - Hamann, Maria A1 - Völler, Heinz A1 - Salzwedel, Annett T1 - Effect of multicomponent rehabilitation on independence and functioning in elderly patients with common age-associated diseases BT - protocol for a scoping review (REHOLD) JF - BMJ open N2 - Introduction Elderly patients after hospitalisation for acute events on account of age-related diseases (eg, joint or heart valve replacement surgery) are often characterised by a remarkably reduced functional health. Multicomponent rehabilitation (MR) is considered an appropriate approach to restore the functioning of these patients. However, its efficacy in improving functioning-related outcomes such as care dependency, activities of daily living (ADL), physical function and health-related quality of life (HRQL) remains unclarified. We outline the research framework of a scoping review designed to map the available evidence of the effects of MR on the independence and functional capacity of elderly patients hospitalised for age-related diseases in four main medical specialties beyond geriatrics. Methods and analysis The biomedical databases (PubMed, Cochrane Library, ICTRP Search Platform, ClinicalTrials) and additionally Google Scholar will be systematically searched for studies comparing centre-based MR with usual care in patients ≥75 years of age, hospitalised for common acute events due to age-related diseases (eg, joint replacement, stroke) in one of the specialties of orthopaedics, oncology, cardiology or neurology. MR is defined as exercise training and at least one additional component (eg, nutritional counselling), starting within 3 months after hospital discharge. Randomised controlled trials as well as prospective and retrospective controlled cohort studies will be included from inception and without language restriction. Studies investigating patients <75 years, other specialties (eg, geriatrics), rehabilitation definition or differently designed will be excluded. Care dependency after at least a 6-month follow-up is set as the primary outcome. Physical function, HRQL, ADL, rehospitalisation and mortality will be additionally considered. Data for each outcome will be summarised, stratified by specialty, study design and type of assessment. Furthermore, quality assessment of the included studies will be performed. Ethics and dissemination Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at national and/or international congresses. Y1 - 2023 U6 - https://doi.org/10.1136/bmjopen-2022-068722 SN - 2044-6055 VL - 13 IS - 5 PB - BMJ Publishing Group CY - London ER - TY - JOUR A1 - Barucha, Anton A1 - Mauch, Renan Marrichi A1 - Duckstein, Franziska A1 - Zagoya, Carlos A1 - Mainz, Jochen G. T1 - The potential of volatile organic compound analysis for pathogen detection and disease monitoring in patients with cystic fibrosis JF - Expert review of respiratory medicine N2 - Introduction Airway infection with pathogens and its associated pulmonary exacerbations (PEX) are the major causes of morbidity and premature death in cystic fibrosis (CF). Preventing or postponing chronic infections requires early diagnosis. However, limitations of conventional microbiology-based methods can hamper identification of exacerbations and specific pathogen detection. Analyzing volatile organic compounds (VOCs) in breath samples may be an interesting tool in this regard, as VOC-biomarkers can characterize specific airway infections in CF. Areas covered We address the current achievements in VOC-analysis and discuss studies assessing VOC-biomarkers and fingerprints, i.e. a combination of multiple VOCs, in breath samples aiming at pathogen and PEX detection in people with CF (pwCF). We aim to provide bases for further research in this interesting field. Expert opinion Overall, VOC-based analysis is a promising tool for diagnosis of infection and inflammation with potential to monitor disease progression in pwCF. Advantages over conventional diagnostic methods, including easy and non-invasive sampling procedures, may help to drive prompt, suitable therapeutic approaches in the future. Our review shall encourage further research, including validation of VOC-based methods. Specifically, longitudinal validation under standardized conditions is of interest in order to ensure repeatability and enable inclusion in CF diagnostic routine. KW - Breath analysis KW - cystic fibrosis KW - pathogens KW - Pseudomonas aeruginosa KW - volatile organic compounds Y1 - 2022 U6 - https://doi.org/10.1080/17476348.2022.2104249 SN - 1747-6348 SN - 1747-6356 VL - 16 IS - 7 SP - 723 EP - 735 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Blaser, Berenike Lisa A1 - Weymar, Mathias A1 - Wendt, Julia T1 - The effect of a single-session heart rate variability biofeedback on attentional control BT - does stress matter? JF - Frontiers in psychology N2 - Introduction Vagally mediated heart rate variability is an index of autonomic nervous system activity that is associated with a large variety of outcome variables including psychopathology and self-regulation. While practicing heart rate variability biofeedback over several weeks has been reliably associated with a number of positive outcomes, its acute effects are not well known. As the strongest association with vagally mediated heart rate variability has been found particularly within the attention-related subdomain of self-regulation, we investigated the acute effect of heart rate variability biofeedback on attentional control using the revised Attention Network Test. Methods Fifty-six participants were tested in two sessions. In one session each participant received a heart rate variability biofeedback intervention, and in the other session a control intervention of paced breathing at a normal ventilation rate. After the biofeedback or control intervention, participants completed the Attention Network Test using the Orienting Score as a measure of attentional control. Results Mixed models revealed that higher resting baseline vagally mediated heart rate variability was associated with better performance in attentional control, which suggests more efficient direction of attention to target stimuli. There was no significant main effect of the intervention on attentional control. However, an interaction effect indicated better performance in attentional control after biofeedback in individuals who reported higher current stress levels. Discussion The results point to acute beneficial effects of heart rate variability biofeedback on cognitive performance in highly stressed individuals. Although promising, the results need to be replicated in larger or more targeted samples in order to reach stronger conclusions about the effects. KW - attention KW - self-regulation KW - heart rate variability KW - biofeedback KW - cognitive control KW - stress KW - vagal tone KW - slow-paced breathing Y1 - 2023 U6 - https://doi.org/10.3389/fpsyg.2023.1292983 SN - 1664-1078 VL - 14 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Cassel, Michael A1 - Risch, Lucie A1 - Intziegianni, Konstantina A1 - Mueller, Juliane A1 - Stoll, Josefine A1 - Brecht, Pia A1 - Mayer, Frank T1 - Incidence of achilles and patellar tendinopathy in adolescent elite athletes JF - International journal of sports medicine N2 - The study investigated the incidence of Achilles and patellar tendinopathy in adolescent elite athletes and non-athletic controls. Furthermore, predictive and associated factors for tendinopathy development were analyzed. The prospective study consisted of two measurement days (M1/M2) with an interval of 3.2 +/- 0.9 years. 157 athletes (12.1 +/- 0.7 years) and 25 controls (13.3 +/- 0.6 years) without Achilles/patellar tendinopathy were included at Ml. Clinical and ultrasound examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main outcome measures were incidence tendinopathy and structural intratendinous alterations (hypo-/hyperechogenicity, vascularization) at M2 [%]. Incidence of Achilles tendinopathy was 1% in athletes and 0% in controls. Patellar tendinopathy was more frequent in athletes (13 %)than in controls (4%). Incidence of intratendinous alterations in ATs was 1-2% in athletes and 0 % in controls, whereas in PTs it was 4-6 % in both groups (p >0.05). Intratendinous alterations at M2 were associated with patellar tendinopathy in athletes (p <= 0.01). Intratendinous alterations at M1, anthropometric data, training amount, sports or sex did not predict tendinopathy development (p>0.05). Incidence often dinopathy and intratendinous alterations in adolescent athletes is low in ATs and more common in PTs. Development of intratendinous alterations in PT is associated with tend in opathy. However, predictive factors could not be identified. KW - epidemiology KW - young athletes KW - sonography KW - vascularization KW - hypoechogenicities Y1 - 2018 U6 - https://doi.org/10.1055/a-0633-9098 SN - 0172-4622 SN - 1439-3964 VL - 39 IS - 9 SP - 726 EP - 732 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - D'Agostini, Martina A1 - Burger, Andreas M. A1 - Franssen, Mathijs A1 - Claes, Nathalie A1 - Weymar, Mathias A1 - Leupoldt, Andreas von A1 - Van Diest, Ilse T1 - Effects of transcutaneous auricular vagus nerve stimulation on reversal learning, tonic pupil size, salivary alpha-amylase, and cortisol JF - Psychophysiology : journal of the Society for Psychophysiological Research N2 - 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. KW - cortisol KW - noradrenaline KW - pupillometry KW - reversal learning KW - salivary KW - alpha-amylase KW - transcutaneous auricular vagus nerve stimulation Y1 - 2021 U6 - https://doi.org/10.1111/psyp.13885 SN - 1469-8986 SN - 1540-5958 VL - 58 IS - 10 PB - Wiley-Blackwell CY - Malden, Mass. [u.a.] ER - TY - JOUR A1 - Deutschmann, Claudia A1 - Roggenbuck, Dirk A1 - Schierack, Peter A1 - Rödiger, Stefan T1 - Autoantibody testing by enzyme-linked immunosorbent assay-a case in which the solid phase decides on success and failure JF - Heliyon N2 - Background: The enzyme-linked immunosorbent assay (ELISA) is an indispensable tool for clinical diagnostics to identify or differentiate diseases such as autoimmune illnesses, but also to monitor their progression or control the efficacy of drugs. One use case of ELISA is to differentiate between different states (e.g. healthy vs. diseased). Another goal is to quantitatively assess the biomarker in question, like autoantibodies. Thus, the ELISA technology is used for the discovery and verification of new autoantibodies, too. Of key interest, however, is the development of immunoassays for the sensitive and specific detection of such biomarkers at early disease stages. Therefore, users have to deal with many parameters, such as buffer systems or antigen-autoantibody interactions, to successfully establish an ELISA. Often, fine-tuning like testing of several blocking substances is performed to yield high signal-to-noise ratios.
Methods: We developed an ELISA to detect IgA and IgG autoantibodies against chitinase-3-like protein 1 (CHI3L1), a newly identified autoantigen in inflammatory bowel disease (IBD), in the serum of control and disease groups (n = 23, respectively). Microwell plates with different surface modifications (PolySorp and MaxiSorp coating) were tested to detect reproducibility problems.
Results: We found a significant impact of the surface properties of the microwell plates. IgA antibody reactivity was significantly lower, since it was in the range of background noise, when measured on MaxiSorp coated plates (p < 0.0001). The IgG antibody reactivity did not differ on the diverse plates, but the plate surface had a significant influence on the test result (p = 0.0005).
Conclusion: With this report, we want to draw readers' attention to the properties of solid phases and their effects on the detection of autoantibodies by ELISA. We want to sensitize the reader to the fact that the choice of the wrong plate can lead to a false negative test result, which in turn has serious consequences for the discovery of autoantibodies. KW - biochemistry KW - coatings KW - surface chemistry KW - immunology KW - proteins KW - laboratory medicine KW - clinical research KW - enzyme-linked immunosorbent KW - assay KW - biomarker discovery KW - reproducibility KW - solid-phase KW - autoantibody Y1 - 2020 U6 - https://doi.org/10.1016/j.heliyon.2020.e03270 SN - 2405-8440 VL - 6 IS - 1 PB - Elsevier CY - London [u.a.] ER - TY - JOUR A1 - Dobberke, Jeanette A1 - Baritello, Omar A1 - Hadzic, Miralem A1 - Völler, Heinz A1 - Eichler, Sarah A1 - Salzwedel, Annett T1 - Test-retest reliability of center of pressure measures for postural control assessment in older cardiac patients JF - Gait & posture : official journal of Gait and Clinical Movement Analysis Society (GCMAS) and European Society of Movement Analysis in Adults and Children (ESMAC) N2 - Background Elderly patients are a growing population in cardiac rehabilitation (CR). As postural control declines with age, assessment of impaired balance is important in older CR patients in order to predict fall risk and to initiate counteracting steps. Functional balance tests are subjective and lack adequate sensitivity to small differences, and are further subject to ceiling effects. A quantitative approach to measure postural control on a continuous scale is therefore desirable. Force plates are already used for this purpose in other clinical contexts, therefore could be a promising tool also for older CR patients. However, in this population the reliability of the assessment is not fully known. Research question Analysis of test-retest reliability of center of pressure (CoP) measures for the assessment of postural control using a force plate in older CR patients. Methods 156 CR patients (> 75 years) were enrolled. CoP measures (path length (PL), mean velocity (MV), and 95% confidence ellipse area (95CEA)) were analyzed twice with an interval of two days in between (bipedal narrow stance, eyes open (EO) and closed (EC), three trials for each condition, 30 s per trial), using a force plate. For test-retest reliability estimation absolute differences (& UDelta;: T0-T1), intraclass correlation coefficients (ICC) with 95% confidence intervals, standard error of measurement and minimal detectable change were calculated. Results Under EO condition ICC were excellent for PL and MV (0.95) and good for 95CEA (0.88) with & UDelta; of 10.1 cm (PL), 0.3 cm/sec (MV) and 1.5 cm(2 )(95CEA) respectively. Under EC condition ICC were excellent (> 0.95) for all variables with larger & UDelta; (PL: 21.7 cm; MV: 0.7 cm/sec; 95CEA: 2.4 cm(2)) Significance In older CR patients, the assessment of CoP measures using a force plate shows good to excellent test retest reliability. KW - Cardiac rehabilitation KW - Older patients KW - Postural control KW - Test-retest KW - reliability KW - Force plate Y1 - 2022 U6 - https://doi.org/10.1016/j.gaitpost.2021.12.011 SN - 0966-6362 SN - 1879-2219 VL - 92 SP - 359 EP - 363 PB - Elsevier Science CY - Amsterdam ER - TY - JOUR A1 - Dordevic, Milos A1 - Hölzer, Sonja A1 - Russo, Augusta A1 - García Alanis, José Carlos A1 - Müller, Notger Germar T1 - The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study JF - Life N2 - As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding. KW - precuneus KW - spatial updating KW - TMS KW - cTBS Y1 - 2022 U6 - https://doi.org/10.3390/life12081239 SN - 2075-1729 VL - 12 SP - 1 EP - 13 PB - MDPI CY - Basel, Schweiz ET - 8 ER -