@article{AlmeidaRanisch2022, author = {Almeida, Mara and Ranisch, Robert}, title = {Beyond safety: mapping the ethical debate on heritable genome editing interventions}, series = {Humanities and Social Sciences Communications}, volume = {9}, journal = {Humanities and Social Sciences Communications}, number = {1}, publisher = {Springer Nature}, address = {London}, issn = {2662-9992}, doi = {10.1057/s41599-022-01147-y}, pages = {14}, year = {2022}, abstract = {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.}, language = {en} } @article{BaritelloSalzwedelSuendermannetal.2021, author = {Baritello, Omar and Salzwedel, Annett and S{\"u}ndermann, Simon and Niebauer, Josef and V{\"o}ller, Heinz}, title = {The Pandora's Box of frailty assessments: Which is the best for clinical purposes in TAVI patients? A critical review}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, edition = {19}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2077-0383}, doi = {10.3390/jcm10194506}, pages = {1 -- 17}, year = {2021}, abstract = {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}, language = {en} } @article{BaruchaMauchDucksteinetal.2022, author = {Barucha, Anton and Mauch, Renan Marrichi and Duckstein, Franziska and Zagoya, Carlos and Mainz, Jochen G.}, title = {The potential of volatile organic compound analysis for pathogen detection and disease monitoring in patients with cystic fibrosis}, series = {Expert review of respiratory medicine}, volume = {16}, journal = {Expert review of respiratory medicine}, number = {7}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1747-6348}, doi = {10.1080/17476348.2022.2104249}, pages = {723 -- 735}, year = {2022}, abstract = {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.}, language = {en} } @article{CasselRischIntziegiannietal.2018, author = {Cassel, Michael and Risch, Lucie and Intziegianni, Konstantina and Mueller, Juliane and Stoll, Josefine and Brecht, Pia and Mayer, Frank}, title = {Incidence of achilles and patellar tendinopathy in adolescent elite athletes}, series = {International journal of sports medicine}, volume = {39}, journal = {International journal of sports medicine}, number = {9}, publisher = {Thieme}, address = {Stuttgart}, issn = {0172-4622}, doi = {10.1055/a-0633-9098}, pages = {726 -- 732}, year = {2018}, abstract = {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.}, language = {en} } @article{D'AgostiniBurgerFranssenetal.2021, author = {D'Agostini, Martina and Burger, Andreas M. and Franssen, Mathijs and Claes, Nathalie and Weymar, Mathias and Leupoldt, Andreas von and Van Diest, Ilse}, title = {Effects of transcutaneous auricular vagus nerve stimulation on reversal learning, tonic pupil size, salivary alpha-amylase, and cortisol}, series = {Psychophysiology : journal of the Society for Psychophysiological Research}, volume = {58}, journal = {Psychophysiology : journal of the Society for Psychophysiological Research}, number = {10}, publisher = {Wiley-Blackwell}, address = {Malden, Mass. [u.a.]}, issn = {1469-8986}, doi = {10.1111/psyp.13885}, pages = {20}, year = {2021}, abstract = {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.}, language = {en} } @article{DeutschmannRoggenbuckSchieracketal.2020, author = {Deutschmann, Claudia and Roggenbuck, Dirk and Schierack, Peter and R{\"o}diger, Stefan}, title = {Autoantibody testing by enzyme-linked immunosorbent assay-a case in which the solid phase decides on success and failure}, series = {Heliyon}, volume = {6}, journal = {Heliyon}, number = {1}, publisher = {Elsevier}, address = {London [u.a.]}, issn = {2405-8440}, doi = {10.1016/j.heliyon.2020.e03270}, pages = {6}, year = {2020}, abstract = {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.}, language = {en} } @article{DobberkeBaritelloHadzicetal.2022, author = {Dobberke, Jeanette and Baritello, Omar and Hadzic, Miralem and V{\"o}ller, Heinz and Eichler, Sarah and Salzwedel, Annett}, title = {Test-retest reliability of center of pressure measures for postural control assessment in older cardiac patients}, series = {Gait \& posture : official journal of Gait and Clinical Movement Analysis Society (GCMAS) and European Society of Movement Analysis in Adults and Children (ESMAC)}, volume = {92}, journal = {Gait \& posture : official journal of Gait and Clinical Movement Analysis Society (GCMAS) and European Society of Movement Analysis in Adults and Children (ESMAC)}, publisher = {Elsevier Science}, address = {Amsterdam}, issn = {0966-6362}, doi = {10.1016/j.gaitpost.2021.12.011}, pages = {359 -- 363}, year = {2022}, abstract = {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.}, language = {en} } @article{DordevicHoelzerRussoetal.2022, author = {Dordevic, Milos and H{\"o}lzer, Sonja and Russo, Augusta and Garc{\´i}a Alanis, Jos{\´e} Carlos and M{\"u}ller, Notger Germar}, title = {The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study}, series = {Life}, volume = {12}, journal = {Life}, edition = {8}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2075-1729}, doi = {10.3390/life12081239}, pages = {1 -- 13}, year = {2022}, abstract = {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.}, language = {en} } @article{DrobyshevSolovyevGorokhovskiyetal.2018, author = {Drobyshev, Evgenii J. and Solovyev, Nikolay D. and Gorokhovskiy, Boris M. and Kashuro, Vadim A.}, title = {Accumulation Patterns of Sub-chronic Aluminum Toxicity Model After Gastrointestinal Administration in Rats}, series = {Biological Trace Element Research}, volume = {185}, journal = {Biological Trace Element Research}, number = {2}, publisher = {Humana Press Inc.}, address = {Totowa}, issn = {0163-4984}, doi = {10.1007/s12011-018-1247-8}, pages = {384 -- 394}, year = {2018}, abstract = {Although aluminum chronic neurotoxicity is well documented, there are no well-established experimental protocols of Al exposure. In the current study, toxic effects of sub-chronic Al exposure have been evaluated in outbreed male rats (gastrointestinal administration). Forty animals were used: 10 were administered with AlCl3 water solution (2 mg/kg Al per day) for 1 month, 10 received the same concentration of AlCl3 for 3 month, and 20 (10 per observation period) saline as control. After 30 and 90 days, the animals underwent behavioral tests: open field, passive avoidance, extrapolation escape task, and grip strength. At the end of the study, the blood, liver, kidney, and brain were excised for analytical and morphological studies. The Al content was measured by inductively coupled plasma mass-spectrometry. Essential trace elements-Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, and Zn-were measured in whole blood samples. Although no morphological changes were observed in the brain, liver, or kidney for both exposure terms, dose-dependent Al accumulation and behavioral differences (increased locomotor activity after 30 days) between treatment and control groups were indicated. Moreover, for 30 days exposure, strong positive correlation between Al content in the brain and blood for individual animals was established, which surprisingly disappeared by the third month. This may indicate neural barrier adaptation to the Al exposure or the saturation of Al transport into the brain. Notably, we could not see a clear neurodegeneration process after rather prolonged sub-chronic Al exposure, so probably longer exposure periods are required.}, language = {en} } @article{EllermannMcDowellSchirrenetal.2022, author = {Ellermann, Christin and McDowell, Michelle and Schirren, Clara O. and Lindemann, Ann-Kathrin and Koch, Severine and Lohmann, Mark and Jenny, Mirjam Annina}, title = {Identifying content to improve risk assessment communications within the Risk Profile: Literature reviews and focus groups with expert and non-expert stakeholders}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, edition = {4}, publisher = {Public Library of Science (PLOS)}, address = {San Francisco, California, USA}, issn = {1553-7358}, doi = {10.1371/journal.pone.0266800}, pages = {23}, year = {2022}, abstract = {Objective To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile). Methods A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the "Risk Profile" from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts. Results Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors. Conclusion An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.}, language = {en} }