@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{LiebeDordevicKaufmannetal.2022, author = {Liebe, Thomas and Dordevic, Milos and Kaufmann, J{\"o}rn and Avetisyan, Araks and Skalej, Martin and M{\"u}ller, Notger Germar}, title = {Investigation of the functional pathogenesis of mild cognitive impairment by localisation-based locus coeruleus resting-state fMRI}, series = {Human Brain Mapping}, volume = {43}, journal = {Human Brain Mapping}, edition = {18}, publisher = {Wiley}, address = {New York, NY, USA}, issn = {1097-0193}, doi = {10.1002/hbm.26039}, pages = {5630 -- 5642}, year = {2022}, abstract = {Dementia as one of the most prevalent diseases urges for a better understanding of the central mechanisms responsible for clinical symptoms, and necessitates improvement of actual diagnostic capabilities. The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation-based LC resting-state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, n = 28) and an age-matched healthy control group (n = 29). MCI and control participants could be differentiated in their Mini-Mental-State-Examination (MMSE) scores (p < .001) and LC intensity ratio (p = .010). In the fMRI, LC fc to anterior cingulate cortex (FDR p < .001) and left anterior insula (FDR p = .012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR p = .012) and posterior cingulate cortex (PCC, FDR p = .021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (p = .017). Furthermore, we found a hyperactivation of the left-insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression.}, language = {en} } @book{OPUS4-56684, title = {Drug target miRNA}, series = {Methods in Molecular Biology}, journal = {Methods in Molecular Biology}, editor = {Schmidt, Marco F.}, publisher = {Springer}, address = {New York}, isbn = {978-1-4939-6561-8}, issn = {1064-3745}, doi = {10.1007/978-1-4939-6563-2}, pages = {320}, year = {2017}, abstract = {This volume provides a concise and technical discussion of recently developed approaches to overcome challenges in miRNA drug discovery. Drug Target miRNA: Methods and Protocols explores strategies to overcome pharmacodynamics and pharmacokinetics challenges. These strategies cover anti-sense agents targeting miRNA that are applied in advanced formulations or are chemically optimized to increase delivery; small molecule miRNA modulators to overcome anti-sense agents' limitations; general enhancers of miRNA maturation; and Argonaute 2 protein and its pharmacokinetic parameters. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.Cutting-edge and thorough, Drug Target miRNA: Methods and Protocols is a valuable resource for anyone interested in the ever-evolving field of miRNA drug discovery.}, 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{WiebkingLinWippert2022, author = {Wiebking, Christine and Lin, Chiao-I and Wippert, Pia-Maria}, title = {Training intervention effects on cognitive performance and neuronal plasticity — A pilot study}, series = {Frontiers in Neurology, section Neurorehabilitation}, volume = {13}, journal = {Frontiers in Neurology, section Neurorehabilitation}, publisher = {Frontiers}, address = {Lausanne, Schweiz}, issn = {1664-2295}, doi = {10.3389/fneur.2022.773813}, pages = {11}, year = {2022}, abstract = {Studies suggest that people suffering from chronic pain may have altered brain plasticity, along with altered functional connectivity between pain-processing brain regions. These may be related to decreased mood and cognitive performance. There is some debate as to whether physical activity combined with behavioral therapy (e.g. cognitive distraction, body scan) may counteract these changes. However, underlying neuronal mechanisms are unclear. The aim of the current pilot study with a 3-armed randomized controlled trial design was to examine the effects of sensorimotor training for nonspecific chronic low back pain on (1) cognitive performance; (2) fMRI activity co-fluctuations (functional connectivity) between pain-related brain regions; and (3) the relationship between functional connectivity and subjective variables (pain and depression). Six hundred and sixty two volunteers with non-specific chronic low back pain were randomly allocated to a unimodal (sensorimotor training), multidisciplinary (sensorimotor training and behavioral therapy) intervention, or to a control group within a multicenter study. A subsample of patients (n = 21) from one study center participated in the pilot study presented here. Measurements were at baseline, during (3 weeks, M2) and after intervention (12 weeks, M4 and 24 weeks, M5). Cognitive performance was measured by the Trail Making Test and functional connectivity by MRI. Pain perception and depression were assessed by the Von Korff questionnaire and the Hospital and Anxiety. Group differences were calculated by univariate and repeated ANOVA measures and Bayesian statistics; correlations by Pearson's r. Change and correlation of functional connection were analyzed within a pooled intervention group (uni-, multidisciplinary group). Results revealed that participants with increased pain intensity at baseline showed higher functional connectivity between pain-related brain areas used as ROIs in this study. Though small sample sizes limit generalization, cognitive performance increased in the multimodal group. Increased functional connectivity was observed in participants with increased pain ratings. Pain ratings and connectivity in pain-related brain regions decreased after the intervention. The results provide preliminary indication that intervention effects can potentially be achieved on the cognitive and neuronal level. The intervention may be suitable for therapy and prevention of non-specific chronic low back pain.}, 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} } @article{OseiBlockWippert2022, author = {Osei, Francis and Block, Andrea and Wippert, Pia-Maria}, title = {Association of primary allostatic load mediators and metabolic syndrome (MetS): A systematic review}, series = {Frontiers in Endocrinology}, volume = {13}, journal = {Frontiers in Endocrinology}, publisher = {Frontiers}, address = {Lausanne, Schweiz}, issn = {1664-2392}, doi = {10.3389/fendo.2022.946740}, pages = {16}, year = {2022}, abstract = {Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on cross-sectional and case-control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case-control studies. The included studies had a completeness of reporting score of COR \% = 87.0 ± 6.4\%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50\% (urinary cortisol), 40\% (serum cortisol), 60\% (salivary cortisol), and 100\% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60\% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100\% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS.}, language = {en} } @article{HeroldLabottGraessleretal.2022, author = {Herold, Fabian and Labott, Berit K. and Gr{\"a}ssler, Bernhard and Halfpaap, Nicole and Langhans, Corinna and M{\"u}ller, Patrick and Ammar, Achraf and Dordevic, Milos and H{\"o}kelmann, Anita and M{\"u}ller, Notger Germar}, title = {A Link between Handgrip Strength and Executive Functioning: A Cross-Sectional Study in Older Adults with Mild Cognitive Impairment and Healthy Controls}, series = {Healthcare : open access journal}, volume = {10}, journal = {Healthcare : open access journal}, edition = {2}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2227-9032}, doi = {10.3390/healthcare10020230}, pages = {1 -- 14}, year = {2022}, abstract = {Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A\&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.}, 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{LemaireInfossiChaoucheetal.2018, author = {Lemaire, Olivier N. and Infossi, Pascale and Chaouche, Amine Ali and Espinosa, Leon and Leimk{\"u}hler, Silke and Giudici-Orticoni, Marie-Therese and Mejean, Vincent and Iobbi-Nivol, Chantal}, title = {Small membranous proteins of the TorE/NapE family, crutches for cognate respiratory systems in Proteobacteria}, series = {Scientific reports}, volume = {8}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-31851-2}, pages = {13}, year = {2018}, abstract = {In this report, we investigate small proteins involved in bacterial alternative respiratory systems that improve the enzymatic efficiency through better anchorage and multimerization of membrane components. Using the small protein TorE of the respiratory TMAO reductase system as a model, we discovered that TorE is part of a subfamily of small proteins that are present in proteobacteria in which they play a similar role for bacterial respiratory systems. We reveal by microscopy that, in Shewanella oneidensis MR1, alternative respiratory systems are evenly distributed in the membrane contrary to what has been described for Escherichia coli. Thus, the better efficiency of the respiratory systems observed in the presence of the small proteins is not due to a specific localization in the membrane, but rather to the formation of membranous complexes formed by TorE homologs with their c-type cytochrome partner protein. By an in vivo approach combining Clear Native electrophoresis and fluorescent translational fusions, we determined the 4: 4 stoichiometry of the complexes. In addition, mild solubilization of the cytochrome indicates that the presence of the small protein reinforces its anchoring to the membrane. Therefore, assembly of the complex induced by this small protein improves the efficiency of the respiratory system.}, 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} } @misc{HeWuertzKozakKuehletal.2021, author = {He, Yangyang and Wuertz-Kozak, Karin and Kuehl, Linn K. and Wippert, Pia-Maria}, title = {Extracellular vesicles: potential mediators of psychosocial stress contribution to osteoporosis?}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {11}, issn = {1866-8372}, doi = {10.25932/publishup-52300}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-523007}, pages = {17}, year = {2021}, abstract = {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.}, language = {en} } @article{SalzwedelVoeller2021, author = {Salzwedel, Annett and V{\"o}ller, Heinz}, title = {Cardiac rehabilitation}, series = {Deutsches {\"A}rzteblatt international : a weekly online journal of clinical medicine and public health}, volume = {118}, journal = {Deutsches {\"A}rzteblatt international : a weekly online journal of clinical medicine and public health}, number = {29-30}, publisher = {Dt. {\"A}rzte-Verl.}, address = {Cologne}, organization = {OutCaRe Investigators}, issn = {1866-0452}, doi = {10.3238/arztebl.m2021.0211}, pages = {505 -- 506}, year = {2021}, language = {en} } @article{WitteLinnemannstoensHonemannCapitoetal.2021, author = {Witte, Leonie and Linnemannstoens, Karen and Honemann-Capito, Mona and Groß, Julia Christina}, title = {Visualization and quantitation of Wg trafficking in the Drosophila wing imaginal epithelium}, series = {Bio-protocol}, volume = {11}, journal = {Bio-protocol}, number = {11}, publisher = {bio-protocol.org}, address = {Sunnyvale, CA}, issn = {2331-8325}, doi = {10.21769/BioProtoc.4040}, pages = {16}, year = {2021}, abstract = {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.}, language = {en} } @article{HerzogJennyNickeletal.2020, author = {Herzog, Stefan M. and Jenny, Mirjam A. and Nickel, Christian and Ortega, Ricardo Nieves and Bingisser, Roland}, title = {Emergency department patients with weakness or fatigue}, series = {PLOS ONE}, volume = {15}, journal = {PLOS ONE}, number = {11}, publisher = {Public Library of Science}, address = {San Francisco, California, US}, issn = {1932-6203}, doi = {10.1371/journal.pone.0239902}, pages = {20}, year = {2020}, abstract = {Background Generalized weakness and fatigue are underexplored symptoms in emergency medicine. Triage tools often underestimate patients presenting to the emergency department (ED) with these nonspecific symptoms (Nemec et al., 2010). At the same time, physicians' disease severity rating (DSR) on a scale from 0 (not sick at all) to 10 (extremely sick) predicts key outcomes in ED patients (Beglinger et al., 2015; Rohacek et al., 2015). Our goals were (1) to characterize ED patients with weakness and/or fatigue (W|F); to explore (2) to what extent physicians' DSR at triage can predict five key outcomes in ED patients with W|F; (3) how well DSR performs relative to two commonly used benchmark methods, the Emergency Severity Index (ESI) and the Charlson Comorbidity Index (CCI); (4) to what extent DSR provides predictive information beyond ESI, CCI, or their linear combination, i.e., whether ESI and CCI should be used alone or in combination with DSR; and (5) to what extent ESI, CCI, or their linear combination provide predictive information beyond DSR alone, i.e., whether DSR should be used alone or in combination with ESI and / or CCI. Methods Prospective observational study between 2013-2015 (analysis in 2018-2020, study team blinded to hypothesis) conducted at a single center. We study an all-comer cohort of 3,960 patients (48\% female patients, median age = 51 years, 94\% completed 1-year follow-up). We looked at two primary outcomes (acute morbidity (Bingisser et al., 2017; Weigel et al., 2017) and all-cause 1- year mortality) and three secondary outcomes (in-hospital mortality, hospitalization and transfer to ICU). We assessed the predictive power (i.e., resolution, measured as the Area under the ROC Curve, AUC) of the scores and, using logistic regression, their linear combinations. Findings Compared to patients without W|F (n = 3,227), patients with W|F (n = 733) showed higher prevalences for all five outcomes, reported more symptoms across both genders, and received higher DSRs (median = 4; interquartile range (IQR) = 3-6 vs. median = 3; IQR = 2-5). DSR predicted all five outcomes well above chance (i.e., AUCs > similar to 0.70), similarly well for both patients with and without W|F, and as good as or better than ESI and CCI in patients with and without W|F (except for 1-year mortality where CCI performs better). For acute morbidity, hospitalization, and transfer to ICU there is clear evidence that adding DSR to ESI and/or CCI improves predictions for both patient groups; for 1-year mortality and in-hospital mortality this holds for most, but not all comparisons. Adding ESI and/or CCI to DSR generally did not improve performance or even decreased it. Conclusions The use of physicians' disease severity rating has never been investigated in patients with generalized weakness and fatigue. We show that physicians' prediction of acute morbidity, mortality, hospitalization, and transfer to ICU through their DSR is also accurate in these patients. Across all patients, DSR is less predictive of acute morbidity for female than male patients, however. Future research should investigate how emergency physicians judge their patients' clinical state at triage and how this can be improved and used in simple decision aids.}, language = {en} } @misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, number = {3}, doi = {10.25932/publishup-56732}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-567321}, 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} } @misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, doi = {10.25932/publishup-56554}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-565542}, 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} } @misc{HeroldLabottGraessleretal.2022, author = {Herold, Fabian and Labott, Berit K. and Gr{\"a}ssler, Bernhard and Halfpaap, Nicole and Langhans, Corinna and M{\"u}ller, Patrick and Ammar, Achraf and Dordevic, Milos and H{\"o}kelmann, Anita and M{\"u}ller, Notger Germar}, title = {A Link between Handgrip Strength and Executive Functioning: A Cross-Sectional Study in Older Adults with Mild Cognitive Impairment and Healthy Controls}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, issn = {1866-8364}, doi = {10.25932/publishup-55925}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-559251}, pages = {1 -- 14}, year = {2022}, abstract = {Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A\&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.}, language = {en} } @misc{OseiBlockWippert2022, author = {Osei, Francis and Block, Andrea and Wippert, Pia-Maria}, title = {Association of primary allostatic load mediators and metabolic syndrome (MetS): A systematic review}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, number = {6}, doi = {10.25932/publishup-58176}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-581769}, pages = {16}, year = {2022}, abstract = {Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on cross-sectional and case-control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case-control studies. The included studies had a completeness of reporting score of COR \% = 87.0 ± 6.4\%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50\% (urinary cortisol), 40\% (serum cortisol), 60\% (salivary cortisol), and 100\% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60\% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100\% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS.}, language = {en} } @misc{LiebeDordevicKaufmannetal.2022, author = {Liebe, Thomas and Dordevic, Milos and Kaufmann, J{\"o}rn and Avetisyan, Araks and Skalej, Martin and M{\"u}ller, Notger Germar}, title = {Investigation of the functional pathogenesis of mild cognitive impairment by localisation-based locus coeruleus resting-state fMRI}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Gesundheitswissenschaftliche Reihe}, number = {7}, doi = {10.25932/publishup-58177}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-581772}, pages = {5630 -- 5642}, year = {2022}, abstract = {Dementia as one of the most prevalent diseases urges for a better understanding of the central mechanisms responsible for clinical symptoms, and necessitates improvement of actual diagnostic capabilities. The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation-based LC resting-state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, n = 28) and an age-matched healthy control group (n = 29). MCI and control participants could be differentiated in their Mini-Mental-State-Examination (MMSE) scores (p < .001) and LC intensity ratio (p = .010). In the fMRI, LC fc to anterior cingulate cortex (FDR p < .001) and left anterior insula (FDR p = .012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR p = .012) and posterior cingulate cortex (PCC, FDR p = .021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (p = .017). Furthermore, we found a hyperactivation of the left-insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression.}, language = {en} }